Achilles-Tendinopathy 59f1ffd81723dd19dd45611b PDF

CURRENT CONCEPTS IN ORTHOPAEDICS
Achilles Tendinopathy - CURRENT CONCEPTS
Achilles Tendinopathy
CURRENT CONCEPTS
Editors:
James Calder
Jón Karlsson
Nicola Maffulli
Hajo Thermann
C. Niek van Dijk
PUBLICATIONS
CURRENT CONCEPTS
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CURRENT CONCEPTS
Editors:
James D. Calder
MD, FRCS (Tr & Orth), FFSEM (UK)
Consultant Orthopaedic Surgeon
Chelsea and Westminster Hospital
Imperial College
London, UK
Jon Karlsson
MD, PhD
Professor of Orthopaedics and Sports Traumatology
Department of Orthopaedics
Sahlgrenska University Hospital
Sahlgrenska Academy at Göteborg University
Göteborg, Sweden
Nicola Maffulli
MD, MS, PhD, FRCS
Centre Administrator
Centre for Sports & Exercise Medicine
Barts and The London School of Medicine and Dentistry
Queen Mary College
Mile End Hospital
London, UK
Hajo Thermann
MD, PhD
Centre for Knee and Foot Surgery
Sport Traumatology
Atos Clinic Centre
Heidelberg, Germany
C. Niek van Dijk

MD, PhD
Professor and Chief of Service
Dept. of Orthopaedic Surgery and Traumatology
Academic Medical Centre, University of Amsterdam
Amsterdam, The Netherlands
Achilles Tendinopathy: Current Concepts
LIST OF CONTRIBUTORS
Paul W. Ackermann Otto Chan
MD, PhD FRCR
Associate Professor of Orthopaedic Consultant Interventional Orthopaedic
Surgery Radiologist
Dept. of Orthopaedic Surgery London SportsCare
Karolinska University Hospital and London Independent Hospital
Karolinska Institute London, UK
Stockholm, Sweden
David A. Connell
Håkan Alfredson MBBS, MMED, FRANZCR
MD, PhD, Professor Consultant Interventional Orthopaedic
Sports Medicine Unit Radiologist
Dept. of Surgical and Perioperative The Royal National Orthopaedic Hospital
Science Stanmore, UK
University of Umeå
Umeå, Sweden Tom Crisp
FFSEM
Ösgür A. Atay Consultant Interventional Orthopaedic
MD, Associate Professor Radiologist
Dept. of Orthopaedics & Traumatology London SportsCare
Hacettepe University School of Medicine London Independent Hospital
Ankara, Turkey London, UK
Murat Bozkurt Kay Crossley

MD, Professor BAppSc (Physio), PhD
Dept. of Orthopaedics & Traumatology Dept. of Mechanical Engineering
Ankara Etlik Ihtisas Training and Research Melbourne School of Engineering
Hospital The University of Melbourne
Ankara, Turkey Melbourne, Australia
Annelie Brorsson Brian Donley

PT, MSc MD
Capio Lundby Hospital Director, Centre of Foot and Ankle Surgery
Institute of Clinical Sciences Associate Professor of Surgery
Sahlgrenska Academy Cleveland Clinic, Dept. of Orthopaedic
University of Gothenburg Surgery
Sahlgrenska University Hospital Cleveland, Ohio, USA
Gothenburg, Sweden
Gürhan Dönmez
James D. Calder
MD, FRCS (Tr & Orth), FFSEM (UK)
MD
Dept. of Sports Medicine
Consultant Orthopaedic Surgeon
Hacettepe University School of Medicine
Imperial College Ankara, Turkey
London, UK
List of Contributors
Mahmut N. Doral Jón Karlsson

MD, Professor MD, PhD
Dept. of Orthopaedics & Traumatology Professor of Orthopaedics and Sports
Dept. of Sports Medicine Traumatology
Hacettepe University School of Medicine Dept. of Orthopaedics, Sahlgrenska
Ankara, Turkey University Hospital
Sahlgrenska Academy at Gothenburg
Nicholas R. Forsyth University
MD, PhD Gothenburg, Sweden
Senior Lecturer In Stem Cell Research
The Guy Hilton Research Laboratories Defne Kaya
Keele University Medical School PT, PhD
Stoke-on-Trent, Staffordshire, UK Department of Sports Medicine
Hacettepe University School of Medicine
Rodney B. Hammett Ankara, Turkey
MSc, FRCS
................................ Karim Khan
................................. MD, PhD
................................. Department of Family Practice (Sports
Medicine) and School of Human Kinetics
.................................
University of British Columbia
Vancouver, Canada
David A. Hart
PhD, Professor
McCaig Institute for Bone and Joint Health
John B. King
Dept. of Surgery, University of Calgary FRCS, FFSEM
Consultant Trauma and Orthopaedic
Calgary, Alberta, Canada
Surgeon
Centre for Sports and Exercise Medicine
Jeremiah C Healy Mile End Hospital
FRCP, FRCR, FFSEM London, UK
Consultant Musculoskeletal Radiologist
Justin C. Lee
London, UK
MBBS, MRCS, FRCR
Consultant Musculoskeletal Radiologist
Rebecca J. Kampa Chelsea and Westminster Hospital
BSc (Hons), MBChB, FRCS (Tr & Orth) London, UK
Orthopaedic Clinical Fellow
Upper Extremity Service
Sunnybrook Health Sciences Centre
Umile G. Longo
Toronto, Ontario, Canada
MD
Department of Orthopaedic and Trauma
Surgery
Campus Biomedico University
Rome, Italy
Nicola Maffulli Paul T. Salo

MD, MS, PhD, FRCS MD, FRCSC
Centre Administrator Associate Professor of Orthopaedic
Centre for Sports & Exercise Medicine Surgery
Barts and The London School of Medicine McCaig Institute for Bone and Joint Health
and Dentistry Department of Surgery, University of
Queen Mary College Calgary
Mile End Hospital Calgary, Alberta, Canada
London, UK
Terrence S. Saxby
Adam W.M. Mitchell FRACS
MBBS, FRCS, FRCR Consultant Orthopaedic Surgeon
Consultant Musculoskeletal Radiologist Brisbane Foot and Ankle Centre
Chelsea and Westminster Hospital Arnold Janssen Centre
London, UK Holy Spirit Hospital
..., Australia
Francesco Oliva
MD, PhD Pankaj Sharma
Staff Surgeon MBBS, FRCS (Tr & Orth)
Dept. of Orthopaedics Wessex Deanery
University of Tor Vergata Winchester, UK
Rome, Italy
Karin G. Silbernagel
Mikaa Paavola PT, ATC, PhD
MD, PhD Department of Mechanical Engineering
Department of Surgery University of Delaware
Tampere University Hospital Newark, DE, USA
Tampere, Finland
Hajo Thermann
Nat Padhiar MD, PhD
PhD Centre for Knee and Foot Surgery
Consultant Podiatrist Sport Traumatology
London SportsCare Atos Clinic Centre
London Independent Hospital
Heidelberg, Germany
London, UK
Christopher J. Pearce Roland Thomée

FRCS, MFSEM (UK) PT, Associate Professor
Dept. of Trauma and Orthopaedic Surgery Dept. of Orthopaedics
Basingstoke and North Hampshire Institute of Clinical Sciences
Hospitals Sahlgrenska Academy
NHS Foundation Trust University of Gothenburg
Basingstoke, UK Sahlgrenska University Hospital
Gothenburg, Sweden
Claudio Rosso
MD Egemen Turhan
Orthopaedic Department MD, Assistant Professor
University Hospital of Basel Dept. of Orthopaedics & Traumatology
Switzerland Zonguldak Karaelmas University School of
Medicine
Zonguldak, Turkey
List of Contributors
Victor Valderrabano
MD, PhD
Professor, Director
Orthopaedic Department
University Hospital of Basel
Basel, Switzerland
C. Niek van Dijk

MD, PhD
Professor and Chief of Service
Dept. of Orthopaedic Surgery and
Traumatology
Academic Medical Centre, University of
Amsterdam
Maayke N. van Sterkenburg

MD, PhD fellow
Orthopaedic Research Centre Amsterdam
Dept. of Orthopaedic Surgery
Academic Medical Centre, University of
Amsterdam
Contents
CONTENTS
Preface ...........................................................................................................................................................1
The Editors
1. .................................................................................................................................................3
2. ......................................................................................................................................11
3. .................................................................................................17
4. ..............................................................................................................................................27
5. .....................................................................................................................33
6. ......................................................................................................................................49
7. ..................................................................................................57
8. ........................................................67
9. ................................................................................................................75
10. ................................................................................................81
11. ........................................................................................87
12. ..................................................................................99
13. ....................................................................................................103
14. ........................................................................................107
15. ........................................................................117
Preface
PREFACE
Non-insertional Achilles tendinopathy is an over-use injury and is increasing in
incidence in-part due to the rise in sporting activities. It is said to effect up to 9%
of recreational runners and 3-5% of professional athletes with Achilles tendin-
opathy who are forced to give up their sporting career. The cause of the tendin-
opathy is multifactorial and the underlying pathophysiology complex. Therefore,
the treatment is controversial and has a far from certain outcome – “treatment is
more of an art than a science”.
Many different treatment modalities have been put forward over the years with
varying reported rates of success. Many of these treatments may be based upon
sound scientific theory but most have little clinical evidence to support their use.
The Achilles Tendon Study Group (ATSG) has reviewed the available literature in
an attempt to provide a balanced consensus on what is known about Achilles
tendinopathy, the available treatments (and the basis on which they are found-
ed), the outcome measures available to standardise future clinical studies and
future treatments that are being developed. The ATSG has recruited world lead-
ers who have an interest in the Achilles tendon and present a book summarising
our current knowledge on non-insertional Achilles tendinopathy.
It is acknowledged that some chapters are controversial as they report on treat-

ments that may be widely used but have little clinical support in terms of control-
led or independent studies. The editors have specifically included such chapters
to promote debate and highlight areas where future clinical research is required
or is in progress. The authors also wish to promote new studies on Achilles ten-
don pathology, especially controversial topics.
This is the second in a series of consensus books. The first “Achilles Tendon Rup-
ture” was presented at ESSKA 2008 in Porto and is available free through DJO
Publications. The third book is in preparation “Insertional Achilles Tendinopathy”
and will be released at the ESSKA meeting in 2012.
The Editors
1
2
Epidemiology of Tendinopathy of the Achilles Tendon
“88.2% of all statistics are made up on

the spot... “
(Vic Reeves)
Chapter 1.
Epidemiology of
Tendinopathy of the
Achilles Tendon
Christopher J. Pearce, James D. Calder
Take Home Message
Introduction
The Achilles tendon is the thickest and strongest tendon in the human body.
Its fibres are not arranged vertically but rotate to a variable degree in a spiral
manner7. The main blood supply to the tendon comes proximally from the mus-
culo-tendinous junction and distally from the bony insertion at the os calcis. It is
3
the area of relative avascularity between these two (2-6cm above the insertion)4
where the majority of problems occur.
Great forces are transmitted through the Achilles tendon especially during rigor-
ous activity. An example given in Gray’s anatomy is that for a 70 Kg man running
at middle distance pace the peak force in the tendon is 5000 N, which is enough
to stretch it by 6%8. This is significant if one considers that tendons rupture at
approximately 8% strain.
The term ‘tendinosis’ was used by Puddu32 in 1976 to describe the histological
degenerative changes in the Achilles tendon in this condition. These include a
loss of the normal collagenous architecture and replacement with an amorphous
mucinous material, hypercellularity and increased glycosaminoglycans19. Inflam-
mation has been shown to be largely absent2, 17-19, 31, 33, unless there has been a re-
cent rupture, and therefore the term tendinopathy is preferred to the previously
common used tendinitis20, 28.
Non-insertional Achilles tendinopathy is characterised by pain which is worse at
the beginning of and during sporting activity. There may be a localised swelling
on the tendon, usually about 2-5 cm above the os calcis insertion on the medial
side, which correlates with the maximal area of tenderness on palpation.
Epidemiology
The incidence of tendinopathy of the Achilles tendon and other overuse injuries
is rising, especially in the developed world, as more people regularly participate
in recreational and competitive sports and the duration and intensity of training
regimens increase16, 29, 37. Tendinopathy is the most common pathological condi-
tion in the Achilles tendon and represents between 55 and 65% of the disorders
of it9, 15, 26.
Sport
Athletes, whether elite or recreational, are the most common group of people
to present with non-insertional Achilles tendinopathy. The condition has been
described in association with many different sports activities, but middle and
long-distance runners have the greatest susceptibility to it14, 15, 22, 24, 25, 30, 37. The an-
nual incidence of disorders of the Achilles tendon in high level club runners was
between 7% and 9% in a study by Lysholm and Wiklander27. In a questionnaire
study of former top level athletes, Kujala et al. found a greatly increased cumula-
tive incidence of tendinopathy in middle and long-distance runners compared
to age matched controls, with an adjusted odds ratio of 31.224. Achilles tendon
overuse injury was the predominant injury overall in a recent series of master
running athletes, with an incidence of 0.02 injuries per 1000 km run, a quarter of
all injuries to these athletes22. Non-insertional tendinopathy was twice as com-
mon as insertional tendinopathy. An exposure related incidence was previously
shown by Haglund-Akerlind and Eriksson, where runners with Achilles tendinop-
athy had trained for significantly more years and covered longer distances than
4
runners without Achilles tendon pain11.

A rapid increase in mileage, increased interval training, running on sloping and
slippery roads and even a single intense run have been implemented in contrib-
uting to the problem22, 35.
Athletic activity is not, however, the only predisposing factor to the development
of Achilles tendinopathy - in one series, 18 of 58 patients with ‘achillodynia’ had
no direct association with sports or vigorous physical activity34.
Age
The normal aging process can result in the histological changes of tendinopathy.
This may predispose patients to partial tears and the subsequent development
of the clinical condition1.
Kannus and Jozsa found that in 445 tendons taken at the time of death from the
cadavera of previously healthy individuals who died accidentally, tendinopathic
changes were found in 34%17. Of the young control subjects in this study (mean
age, thirty-eight years), more than 30% had pathological changes in the Achilles
tendon, while almost half of the older control subjects (mean age, sixty-six years)
demonstrated these changes.
Chronic disease
A retrospective study found various statistically significant correlations between

tendinopathy and diabetes mellitus, obesity and hypertension when compared
with controls12.
A recent ultrasound study of the Achilles tendon in a consecutive group of seven-
ty asymptomatic diabetics revealed disorganised tendon fibers in 62 of 70 (89%)
individuals. Nine of the ten control patients had organised Achilles tendon fibers,
and the one control subject whose tendon was not normal had another risk fac-
tor for the condition, as they had undergone three courses of oral ciprofloxacin
therapy3. Fluroquinolone antibiotics, including ciprofloxacin have long been as-
sociated with the development of tendinopathies5, 6, 10, 13, 23, 36, 38, 39.
There is a significant association between Achilles tendinopathy and adult fa-
milial hypercholesterolaemia and mixed hyperlipidaemia compared with age,
sex and race matched controls, and almost two thirds of patients’ symptoms im-
proved after lipid lowering therapy21.
Others
The ABO blood group distribution of patients with a rupture of the Achilles ten-
don (P = 0.030) and of patients with chronic Achilles tendinopathy (P = 0.10) dif-
fered from the controls in a study by Kujala et al with the O and A blood groups
being predominant in the condition.
Women taking the oral contraceptive pill and who were on post-menopausal
5
hormone replacement therapy also appear to have a higher incidence of Achilles

tendinopathy than national controls12.
Conclusion
Tendinopathy of the Achilles tendon is common in athletes, and especially run-

ners, but it is not confined to these individuals. Various other epidemiological
groups have been identified.
References
1. Alfredson H. Chronic midportion Achilles tendinopathy: an update on research and treatment.
Clin Sports Med 2003;22:727-41.
2. Alfredson H, Forsgren S, Thorsen K, Lorentzon R. In vivo microdialysis and immunohistochemical
analyses of tendon tissue demonstrated high amounts of free glutamate and glutamate NMDAR1
receptors, but no signs of inflammation, in Jumper’s knee. J Orthop Res 2001;19:881-6.
3. Batista F, Nery C, Pinzur M, et al. Achilles tendinopathy in diabetes mellitus. Foot & Ankle Int
2008;29:498-501.
4. Carr AJ, Norris SH. The blood supply of the calcaneal tendon. J Bone Joint Surg 1989;71:100-1.
5. Corps AN, Curry VA, Harrall RL, et al. Ciprofloxacin reduces the stimulation of prostaglandin E(2)
output by interleukin-1beta in human tendon-derived cells. Rheumatology (Oxford, England)
2003;42:1306-10.
6. Corps AN, Harrall RL, Curry VA, et al. Ciprofloxacin enhances the stimulation of matrix metallopro-
teinase 3 expression by interleukin-1beta in human tendon-derived cells. A potential mechanism of
fluoroquinolone-induced tendinopathy. Arthritis and rheumatism 2002;46:3034-40.
7. Cummins EJ AB, Carr BW, et al. The structure of the calcaneal tendon (of Achilles) in relation to
orthopaedic surgery. With additional observation on the plantaris muscle. . Surg Gynecol Obstet
1946;83:107-16.
8. Davies MS. In: Sandring S. Gray’s Anatomy. 39th ed: Elsevier Churchill Livingston 1534
9. Fahlstrom M, Lorentzon R, Alfredson H. Painful conditions in the Achilles tendon region in elite
badminton players. Am J Sports Med 2002;30:51-4.
10. Fleisch F, Hartmann K, Kuhn M. Fluoroquinolone-induced tendinopathy: also occurring with levo-
floxacin.
Infection 2000;28:256-7.
11. Haglund-Akerlind Y, Eriksson E. Range of motion, muscle torque and training habits in runners
with and without Achilles tendon problems. Knee Surg Sports Traumatol Arthrosc 1993;1:195-9.
12. Holmes GB, Lin J. Etiologic factors associated with symptomatic achilles tendinopathy. Foot &
Ankle Int 2006;27:952-9.
13. Huston KA. Achilles tendinitis and tendon rupture due to fluoroquinolone antibiotics. New Engl
J Med 1994;331:748.
14. Jarvinen M. Epidemiology of tendon injuries in sports. Clin Sports Med 1992;11:493-504.
15. Jarvinen TA, Kannus P, Maffulli N, Khan KM. Achilles tendon disorders: etiology and epidemiology.
Foot Ankle Clin 2005;10:255-66.
16. Kader D, Saxena A, Movin T, Maffulli N. Achilles tendinopathy: some aspects of basic science and
clinical management. Br J Sports Med 2002;36:239-49.
17. Kannus P, Jozsa L. Histopathological changes preceding spontaneous rupture of a tendon. A con-
trolled study of 891 patients. J Bone Joint Surg Am 1991;73:1507-25.
18. Khan KM, Bonar F, Desmond PM, et al. Patellar tendinosis (jumper’s knee): findings at histopatho-
logic examination, US, and MR imaging. Victorian Institute of Sport Tendon Study Group. Radi-
ol1996;200: 821-7.
19. Khan KM, Cook JL, Bonar F, et al. Histopathology of common tendinopathies. Update and implica-
tions for clinical management. Sports Med 1999;27:393-408.
20. Khan KM, Cook JL, Kannus P, et al. Time to abandon the “tendinitis” myth. BMJ (Clinical research
ed) 2002;324:626-7.
6
21. Klemp P, Halland AM, Majoos FL, Steyn K. Musculoskeletal manifestations in hyperlipidaemia: a
controlled study. Ann Rheum Dis 1993;52:44-8.
22. Knobloch K, Yoon U, Vogt PM. Acute and overuse injuries correlated to hours of training in master
running athletes. Foot & Ankle Int 2008;29:671-6.
23. Koeger AC, Bellaiche L, Roger B. Magnetic resonance imaging in fluoroquinolone induced tendin-
opathy. J Rheumatol 1997;24:1015-7.
24. Kujala UM, Sarna S, Kaprio J. Cumulative incidence of achilles tendon rupture and tendinopathy in
male former elite athletes. Clin J Sport Med 2005;15:133-5.
25. Kvist M. Achilles tendon injuries in athletes. Ann Chir Gynecol 1991;80:188-201.
26. Kvist M. Achilles tendon injuries in athletes. Sports Med 1994;18:173-201.
27. Lysholm J, Wiklander J. Injuries in runners. Am J Sports Med 1987;15:168-71.
28. Maffulli N, Khan KM, Puddu G. Overuse tendon conditions: time to change a confusing terminol-
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29. Maffulli N, Sharma P, Luscombe KL. Achilles tendinopathy: aetiology and management. J Royal
Soc Med 2004;97:472-6.
30. Maffulli N, Testa V, Capasso G, et al. Results of percutaneous longitudinal tenotomy for Achilles
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32. Puddu G, Ippolito E, Postacchini F. A classification of Achilles tendon disease. Am J Sports Med
1976;4:145-50.
33. Riley G. The pathogenesis of tendinopathy. A molecular perspective. Rheumatology (Oxford, Eng-
land) 2004;43:131-42.
34. Rolf C, Movin T. Etiology, histopathology, and outcome of surgery in achillodynia. Foot & Ankle
Int 1997;18:565-9.
35. Schepsis AA, Jones H, Haas AL. Achilles tendon disorders in athletes. Am J Sports Med 2002;30:287-
305.
36. Sendzik J, Shakibaei M, Schafer-Korting M, Stahlmann R. Fluoroquinolones cause changes in ex-
tracellular matrix, signalling proteins, metalloproteinases and caspase-3 in cultured human tendon
cells. Toxicology 2005;212:24-36.
37. Wilder RP, Sethi S. Overuse injuries: tendinopathies, stress fractures, compartment syndrome, and
shin splints. Clin Sports Med 2004;23:55-81.
38. Williams RJ, III, Attia E, Wickiewicz TL, Hannafin JA. The effect of ciprofloxacin on tendon, para-
tenon, and capsular fibroblast metabolism. Am J Sports Med 2000;28:364-9.
39. Zabraniecki L, Negrier I, Vergne P, et al. Fluoroquinolone induced tendinopathy: report of 6 cases.
J Rheumatol 1996;23:516-20.
7
10
Functional Anatomy of the Achilles Tendon
“Achilles absent was Achilles still”
“A surgeon is worth an army

full of other man”
(Homer’s; The Iliad)
Chapter 2.
Functional Anatomy of
the Achilles Tendon
Mahmut N. Doral, Murat Bozkurt, Egemen Turhan, Özgür A. Atay,
Gürhan Dönmez, Defne Kaya
Take Home Message
The Achilles tendon has a complex anatomy due to the composition of three
muscles and inserts to the calcaneus thereby it controls three joint; knee, ankle,
subtalar joint.
The vascularity of the Achilles tendon is poor relatively. The vascular and nerve
supplies with flexor hallucis longus and plantaris tendon are the major compo-
nents of the medial side of this tendon.
Anatomic variations of the sural nerve are important during both open and per-
cutaneous procedures of Achilles tendon surgery.
Next step will be the chapter of the “Anatomy of distal part of Achilles Tendon at
the insertional level“
The Achilles tendon (AT) is the thickest and strongest tendon in the human
body. It begins near the middle of the calf fusing with the gastrocnemius muscle
proximally. It is broad, flat shape near its origin and receives muscle fibers from
soleus almost to its lower end (Figure 1).
11
Figure 1: Posterior view of calf. Achilles Tendon begins near the middle of the calf
fusing with the gastrocnemius muscle proximally. It is broad, flat shape near its
origin and receives muscle fibers from soleus almost to its lower end.
The average length of the AT is 15 cm and ranges from 11-26 cm. The mean
width of the AT is 6.8 cm (4.5-8.6 cm) at its origin gradually becoming thinner at
the midsection being 1.8 cm (1.2-2.6 cm). Then, it becomes more rounded until
approximately 4 cm above the calcaneus before expanding in the shape of a
delta. The mean width of the AT is 3.4 (2.0-4.8 cm) at its insertion to the midpoint
of the posterior surface of the calcaneus (Figure 2).
12
Figure 2: The schematic drawing of the left leg. The horizontal lines and the
percentages used to measure the distances of sural nerve and the small saphenous
vein are marked on the cadaver. AT; Achilles tendon, SN; Sural nerve, SSV; Small
saphenous vein, G; Musculus Gastrocinemius, S; Musculus Soleus, FHL; Musculus
Flexor Hallusis Longus, TP, Musculus Tibialis Posterior, FDL; Musculus Flexor
Digitorum Longus, FL; Musculus Fibularis Longus, FB; Musculus Fibularis Brevis, MM;
Medial Malleolus, LM; Lateral Malleolus.
The AT comprises bundles of collagen fibrils, each wrapped in endotenon, which

in turn are enveloped by an epitenon. Further protection and stability is provided
to the AT by the paratenon, a layer of thin, areolar tissue wrapped around the
epitenon1,10.
The fibers of the AT are not aligned strictly vertically and they display a variable
degree of spiralization. In spanning between the muscle and bone, the fibers
of the AT spiral by up to 90 degrees producing an area of concentrated stress.
The tendinous fibers from the gastrocnemius insert into the posterolateral and
those from soleus insert into the posteromedial aspect of the calcaneus. The
extent of this rotation is determined by the position of fusion between the two
muscles, with a more distal fusion resulting in more rotation. Twisting may cause
constriction of the vascular networks but it also ensures less fiber buckling when
the tendon is lax and less deformation of individual strands when under tension.
The result is that fiber distortion and interfiber friction may decrease and increase
the overall strength1,7,10.
The blood supply to the AT is poor and there is a deterioration in the nutrition of
the tendon with advancing age6,8. The predominant artery is a recurrent branch
13
of the posterior tibial artery which mainly supplies peritendinous tissues (Figure
3).
PTA
Branch
of PTA
RMM
Figure 3: The predominant artery of the Achilles tendon is a recurrent branch of the
posterior tibial artery which mainly supplies peritendinous tissues.
The peroneal artery, probably through anastomoses with the posterior tibial
artery, makes small contributions. The anterior tibial artery appears not to be
involved. The vascularity of the mid-substance of the tendon is relatively poor,
although some blood enters the tendon at this point through its anterior surface.
Whilst the paratenon is known to be a highly vascular tissue, disagreement exists
as to whether the vessels are uniformly distributed throughout its length, or allow
for greater blood flow at the site of insertion. The proximal third of the tendon
receives additional blood supply through vessels of the muscle bellies continuing
into the endotenon, although this contribution is not believed to be significant.
The distal third of the tendon receives additional vascularisation, the majority of
which is supplied by small vessels, fed by the fibular and posterior tibial arteries.
This supply starts at the margin of the insertion, continuing proximally up the
endotenon for approximately 2 cm. The vascular territories can also be classified
simply in three, with the midsection supplied by the peroneal artery, and the
proximal and distal sections supplied by the posterior tibial artery. Despite the
existing discrepancies in the literature the area of relative avascularity in the mid-
substance of the tendon is where the majority of problems occur2,9.
The AT is subcutaneous. The sural nerve crosses its lateral border at about half
length of the AT. However, it has many anatomic variations and it is especially
vulnerable here to iatrogenic injury during surgery1,4. Distally, there are bursae
superficial and deep to the tendon. The most common is the retrocalcaneal bursa,
which lies between the AT and the posterior surface of the calcaneus. An almost
14
constant finding, it has an anterior bursal wall composed of fibrocartilage and a

thin posterior wall which blends with the thin epitenon of the AT. Less common
are an adventitious bursa superficial to the AT, and a subcalcaneal bursa between
the inferior surface of the calcaneus and the origin of the plantar aponeurosis.
The muscle belly of flexor hallucis longus (FHL) lies deep to the deep fascia on
the anterior surface of the tendon10,11. Anterior to the AT, there is a wedge of fat
adjacent to the calcaneus. This fat tissue which is also known as “Kager’s fat pad”
has parts related to the AT and FHL tendons. Fibrous connections linking the fat
to the AT anchor and stabilize it proximally and thus contribute to the motility of
its tip12.
The Plantaris is placed between the Gastrocnemius and Soleus. It arises from the
lower part of the lateral prolongation of the linea aspera, and from the oblique
popliteal ligament of the knee-joint. It forms a small fusiform belly, from 7 to 10
cm long, ending in a long slender tendon which crosses obliquely between the
two muscles of the calf, and runs along the medial border of the tendo calcaneus,
to be inserted with it into the posterior part of the calcaneus. This muscle is
sometimes double, and at other times wanting. According to Sarrafians’ atlas of
foot and ankle anatomy, 4% of plantaris tendons insert on the medial border of
the AT, 1-16 cms above its insertion into the calcaneum. Occasionally, its tendon
is lost in the laciniate ligament, or in the fascia of the leg. The plantaris muscle,
particularly the tendinous portion is an important structure in Achilles tendon
surgery. This tendon may be the preferred graft for augmentation of repairs3,5.
Although the AT is the most strong and thick tendon in the human body, its
blood supply is limited. It is prone to degenerative pathologies and ruptures and
therefore the role of ultrastuctural fiber anatomy and paratenon histology of AT
should be examined by further studies.
Acknowledgement
We thank to N. Apaydın MD from Ankara University Department of Anatomy

for her rigorous anatomic dissections of Achilles Tendon on cadaver and to Prof.
N. Maffulli., MD, A. Öçgüder., MD, U. Diliçıkık., MD, U. Mermerkaya., MD for their
scientific supports.
The authors warrant that the materials at the manuscript are original and have
not been used in any other publication before. The authors also confirm that they
are the sole holder of copyrights and that the copyrights of third parties are not
infringed.
15
References
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the calcaneal tendon: an anatomical study with surgical and clinical implications. Surg Radiol Anat.
2009, Epub ahead of print.
2. Chen TM, Rozen WM, Pan WR, Ashton MW, Richardson MD, Taylor GI. The arterial anatomy of the
Achilles tendon: Anatomical study and clinical implications. Clin Anat. 2009;22:377-85.
3. Cummings JE, Anson JB, Carr WB, Wright RR, Houser. DWE. The structure of the calcaneal tendon (of.
Achilles) in relation to orthopedic surgery with additional observations on the plantaris muscle. Surg
Gynecol Obstet. 1946;83:107-16.
4. Doral MN, Bozkurt M, Turhan E, Ayvaz M, Atay OA, Uzumcugil A, Leblebicioğlu G, Kaya D, Aydoğ T.
Percutaneous suturing of the ruptured Achilles tendon with endoscopic control. Arch Orthop Trauma
Surg. 2009;129: 1093-101.
5. Standring S. Gray’s Anatomy: The Anatomical Basis of Clinical Practice. 39th Ed. Philadelphia:
Elsevier Churchill Livingstone;2005.1499-1500.
6. Hastad K, Larsson LG, Lindholm A.;Clearance of radiosodium after local deposit in the Achilles
tendon. Acta Chir Scand. 1959;116:251-5.
7. Jorza LG, Kannus P. Human tendons: anatomy, physiology and pathology. Human kinetics.
Champaigne;1997.
8. Maffulli N. Rupture of the Achilles tendon. J Bone Joint Surg Am. 1999;81:1019-36. Review.
9. Shaw HM, Vazquez OT, McGonagle D, Bydder G, Santer RM, Benjamin M. Development of the
human Achilles tendon enthesis organ. J Anat. 2008;213:718-24.
10. Standring S. 2009. Gray’s Anatomy. 40th edition Churhill Livingstone, Edinburgh.
11. Stein V, Laprell H, Tinnemeyer S, Peterson W. Quantitative assessment of intravascular volume of
the human Achilles tendon. Acta Orthop Scand 2000;71:60-3.
12. Theobald P, Bydder G, Dent C, Nokes L, Pugh N, Benjamin M. The functional anatomy of Kager’s
fat pad in relation to retrocalcaneal problems and other hindfoot disorders. J Anat. 2006;208:91-7.
16
Aetiology of Tendinopathy of the Achilles Tendon: Mechano-Neuro-Biological Interactions
“As your thoughts will steer you - I will be

able to help steer you from time to time.
So now I have been given a task - as your
‘guide’...”
(Publius)
Chapter 3.
Aetiology of Tendinopathy
of the Achilles Tendon:
Mechano-Neuro-
Biological Interactions
Paul W. Ackermann, Umile G. Longo, Nicola Maffulli
Take Home Message
• Appropriate loading and adaptation increases cross-sectional area and tensile

strength of the tendons, while immobilization and inappropriate adaptation
leads to tendon degeneration and tendinopathy.
• External forces like mechanical loading to the tendon, can be transduced by the
peripheral nervous system and its messengers to produce tissue adaptive
changes – either physiological or pathological.
• Mechano-neuro-biological pathways may establish new markers for “tendon
health”, and most interestingly open for new strategies for pharmacological and
physical promotion of tendon repair.
Mechano-transduction
Mechanobiology studies changes in tissue structure and function following

application of mechanical forces, including gravity, tension, compression,
hydrostatic pressure, and fluid shear stress. All these modalities may modulate
morphological and structural fitness of the musculoskeletal tissues, including
bone, cartilage, ligament and tendon. In general, biomechanics encompasses
17
the concepts of mechanobiology, but mechanobiology shifts the emphasis from

mechanics to biology and to determining the mechanisms behind the statement
that ‘form follows function’. In mechanobiology, the central question is, how
these same load-bearing tissues are actively produced, maintained and adapted
by tissue cells as a response to biophysical stimuli in their environment. The
ability of connective tissues, such as tendons, to alter their structure in response
to mechanical loading is named tissue mechanical adaptation. Adaptation
is effected by different cells in the tissues at all times. However, we still do not
completely understand the mechanotransduction mechanisms by which cells
perceive the mechanical forces to which they are subjected and convert them
into the biochemical signals which will lead to tissue adaptive physiological or
pathological changes.
Tendons transmit muscle forces to bone, allowing locomotion and enhancing
joint stability. Tendons do not behave as rigid links between muscles and
bones, but exhibit viscoelastic behaviour. They respond to mechanical forces
by changing their metabolism and their structural and mechanical properties.
Tendons are subjected to dynamic mechanical forces in vivo, and hence
tendons have fibre patterns and viscoelastic characteristics that contribute to
their unique mechanical behaviour. As other soft tissues, including ligaments
and skin, being viscoelastic, tendons are sensitive to different strain rates.
The viscoelastic behaviour of tendons likely results from collagen, water, and
interactions between collagenous proteins and non-collagenous proteins such
as proteoglycans. The viscoelasticity of a material is defined by stress-relaxation,
creep, and hysteresis16. Given their viscoelasticity, tendons are more deformable
at low strain rates. Therefore, at low strain rates tendons absorb more energy,
but are less effective in transferring loads. At high strain rates, they become less
deformable with a high degree of stiffness, and are more effective in moving
large loads27. Tendons change structure in response to the functional demands
imposed on them. Appropriate physical training increases cross-sectional
area and tensile strength of the tendons, with tendon fibroblasts increasing
the production of collagen type I32, 39, 52, 54. On the other hand, inappropriate
physical training leads to tendon overuse injuries and tendinopathy29, 36. Training
also induces biochemical changes in tendons. For example, after strenuous
endurance training for 8 weeks, collagen deposition in the Achilles tendon in
roosters increased by 46% and the collagen contained 50% fewer pyridinoline
cross-links18. Strenuous endurance training therefore increases collagen turnover
and decreases collagen maturation in tendons. Exercise stimulates tenocytes in
the rat Achilles tendon to increase the expression of insulin-like growth factor-I
(IGF-I)25. IGF-I is a potent stimulus to collagen synthesis and cell proliferation49,
53
. Hence, IGF-I may serve as a protein marker for remodelling activities of the
tendon.
Various mediators and also other growth factors in the tendon are highly affected
by physical exercise. Thus, during rat Achilles tendon healing, free mobilization
(normal cage activity) as compared to immobilization significantly up-regulates
the tenocyte expression of growth factors (BDNF, bFGF, IGF-1), pro-inflammatory
mediators (COX 1-2, HIF 1a) and extracellular matrix molecules (collagen type
I and III, versican, decorin and biglycan)12, 13. Interestingly, these stimulatory
12
effects of mobilization are associated with an increased expression of sensory

neuropeptide receptors (NK1 and CRLR/RAMP1) in the tendon13. The sensory
neuropeptides (SP and CGRP) have been demonstrated to enhance connective
tissue healing,24, 43 partly by stimulating up-regulation of growth factors (TGF-B),
inflammatory mediators (HIF 1a) and extracellular matrix molecules (collagen type
III)15, 17, 56, 59. It may prove that physical exercise stimulates healing by increasing
the cellular sensitivity to sensory neuropeptide stimulation by up-regulation of
its receptors on trophic cells13,19. In fact, SP has recently been demonstrated to
stimulate the mobilization of stromal-like stem cells that home to a site of injury
and promote healing26.
Using microdialysis techniques, the effect of physical training on human subjects
has also been determined. Training increases the turnover of type I collagen in
the peritendinous region of the Achilles tendon,32 and physical training promotes
both the synthesis and degradation of collagen. The anabolic processes, however,
dominated, with net synthesis of type I collagen in tendon-related tissue. The
effect of disuse and immobilization on tendons is much slower and less dramatic
than on skeletal tissues, because they have slower metabolism and vascularity37.
In general, however, immobilization decreases the total weight of the tendon,
stiffness, and tensile strength9, 54, 55, 58.
However, during tendon healing, the negative effects of immobilization are
much more dramatic. Already after two weeks of immobilization, structure,
biochemical composition and biomechanical strength of the Achilles tendons
are deteriorated. Thus, two weeks of immobilization during healing reduced
the Achilles tendon maximum force by 80%, collagen III mRNA by 90% and
collagen III-like occurrence by 83%14, 45. These findings could to some extent be
explained by a parallel decrease in the expression of different growth factors
and pro-inflammatory molecules12. The down-regulation of growth factors
could presumably in turn be explained by an almost complete reduction in
the expression of sensory neuropeptide receptors after immobilization13. Thus,
sensory neuropeptide (SP) stimulates growth factor production and markedly
enhances tendon healing after local SP injections15, 17, 24, 50.
Tendon overuse injuries, collectively referred to as tendinopathy,28 affect millions
of people in occupational and athletic settings8. Although tendinopathy is
likely caused by intrinsic or extrinsic factors or their combination,31, 42 excessive
mechanical loading is considered a major causation factor. Repetitive submaximal
strains below the failure threshold of the tendon cause tendon microinjuries
and episodes of tendon inflammation. Tendon inflammation from production
of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in response to repetitive
mechanical loading may contribute to the development of tendinopathy29.
In supports of this hypothesis, elevated PGE2 levels are present in the human
tendon after repetitive mechanical loading33. In addition, in vitro repetitive
mechanical loading of human tendon fibroblasts increases the production of
PGE27, 57 and LTB434. Finally, peritendinous injection of PGE1 in the rat Achilles
tendon leads to a histological picture of tendinopathy within the tendon and
inflammation around it51. Injection of PGE2 into the mid-substance of the tendon
induces profound degenerative changes in the tendon matrix30. Interestingly, a
previous study using microdialysis techniques found that the level of PGE2 in
13
the Achilles tendon of human subjects exhibiting symptoms of tendinopathy

was not significantly higher than that of healthy subjects6. It is possible that,
although repetitive submaximal strains below failure threshold cause tendon
microinjuries and episodes of prostaglandin-mediated tendon inflammation,
the prostaglandins are no longer present in the tendon by the time these
microinjuries become clinically evident.
Neuronal Interactions in Tendinopathy
Several interesting abnormalities in the peripheral neuronal innervation have

been detected in biopsies from patients with tendinopathy4. However, a cause-
and-effect relationship is impossible to establish in patient biopsy studies, and
thus a number of animal studies with different models on tendon loading,
overuse and healing have tried to elucidate the cause-and-effect conception.
Notably, these studies reveal an interesting connection between mechanical
loading and neuronal response. This provides data for a mechano-neuronal-
biological transduction mechanism, whereby the peripheral nerve fibers can
sense mechanical load and transduce loading into biological responses, i.e. up-
or down-regulation of different receptors.
Sensory Nerve Ingrowth
Chronic painful tendons exhibit new ingrowth of sensory nerve fibers in the
tendon itself, which is normally aneuronal35, 47. Sensory nerve ingrowth in the
tendon has been observed as a reaction to repetitive loading38 and also as a
response to injury1, 3. Thus, in normal tendon repair, sensory nerve ingrowth is
correlated with increased nociception, which is followed by autonomic nerve
ingrowth, coinciding with decreased nociception and subsequent nerve
retraction3. Hence, the neuronal dysregulation in tendinopathy, characterized
by aberrant increase of sensory nerve sprouting and a deficient autonomic
modulation may reflect a failed healing response, which leads to increased pain
signalling and possibly also to the hyperproliferative/degenerative changes
associated with tendinopathy.
Increase in Sensory Neuropeptides
Immunohistochemical and semi-quantitative assessments have clearly

demonstrated an increased number of sensory substance P (SP)-positive nerve
fibers in tendinopathic tendons35, 47. The increase of SP in tendinopathy may,
in addition to its role in nociception, reflect pro-inflammatory and trophic
actions. Thus, SP regulates vasodilation, plasma extravasation, and release of
cytokines. SP also stimulates proliferation of fibroblasts and endothelial cells,
as well as the production of transforming growth factor β in fibroblasts. Hence,
up-regulation of SP may well contribute to the morphologic changes observed
14
in tendinopathic patients, such as tenocyte metaplasia, hypercellularity, and

presumably neovascularization.
SP receptor neurokinin (NK)-1
The implications of the above mentioned effects of SP are all plausible with
respect to tendon pathology since its receptor, neurokinin (NK)-1, has been
detected in tenocytes, blood vessel walls and in nerve fibers in tendinopathy23.
Notably, the SP receptor NK1 is involved in chondrocyte mechano-transduction
in human articular cartilage40. Presumably, the NK1-receptor will also regulate
tenocyte mechano-transduction, where it may prove that loading leads to cell
proliferation while un-loading leads to cellular break-down, possibly by apoptosis.
In fact, reduced tendon loading during healing leads to a down-regulated
tendon tissue production of NK1, which is related to tendon tissue break-down13.
Whether the SP receptor NK-1 elicits different responses on different tendon cells
depending on the loading conditions, has yet to be investigated in detail.
Decreased Autonomic Innervation
Tendinopathic tendons exhibit a decreased occurrence of sympathetic nerve

fibers, immunopositive to noradrenaline, considered as the main sympathetic
marker (transmitter)2. The reduction in vasoregulatory noradrenaline suggests a
reduced blood flow and a suppressed anti-nociceptive function. Immunoreaction
for the alpha1-adrenoreceptor for noradrenaline has been detected in nerve
fascicles, tenocytes and increased density in blood vessel walls in tendinopathic
patients11,21. Whether the increased occurrence of noradrenaline receptors
in vessels represents a compensatory up-regulation from reduced neuronal
noradrenaline, or just a reflection of the increased number of blood vessels, is
still not fully clarified.
Parasympathetic acetylcholine has also been demonstrated in nerve fibers in
normal and tendinopathic tendons. It is, however, still unclear whether there is
an altered parasympathetic innervation in tendinopathic tendons20, 22.
Increased cellular autonomic mediator production as a response to

decreased innervation?
Compensatory up-regulation of cellular noradrenaline production has been

suggested in morphologically altered tenocytes in tendinopathy patients,
possibly as a result of loading11, 21. Noradrenaline activation of alpha1-
adrenoreceptors stimulates cell proliferation and differentiation. Thus,
noradrenaline may presumably be involved in regulating angiogenesis, nerve
sprouting and tenocyte transformation60.
Likewise the parasympathetic acetylcholine cellular system seems up-regulated
in tendinopathy. Thus, activated markers of cellular acetylcholine production
15
in human tendinopathy were immunohistochemically identified and most

prominently seen in morphologically altered tenocytes. The intensified
immunoreaction to choline acetyltransferase and vesicular acetylcholine
transporter was not detected in normal tenocytes10, 20, 22. Muscarinic acetylcholine
receptors (M2) demonstrate a higher density in morphologically altered
tenocytes in human tendinopathy. M2-receptors have also been identified
in blood vessel walls and nerve fibers in tendinopathy20, 22. This suggests that
decreased neuronal autonomic mediators in tendinopathic patients lead to up-
regulated cellular noradrenaline and acetylcholine, which may both be involved
in regulating tenocyte metaplasia.
Up-regulated Glutamate Receptor-ligand Pathways
Elevated interstitial levels of glutamate have also been found in tendinopathy by

microdialysis5. Furthermore, the specific localization for the increased glutamate
levels has just recently been established in tendinopathic patients46, 48. Thus,
up-regulated glutamate occurrence is observed in morphologically altered
tenocytes, in the endothelial and adventitial layers of blood vessel walls and in
nerve fibers.
One receptor for glutamate, NMDA receptor 1 (NMDAR1) has been identified
in tendinopathy. Recently, both subjective and quantitative assessments
demonstrated a 9-fold increased NMDAR1 occurrence in tendinopathic
patients44. This finding was corroborated by a study on rat supraspinatus tendon
overuse likewise demonstrating NMDAR1 up-regulation41.
Possibly most intriguing finding regarding glutamatergic signalling is the
recent report demonstrating co-existence of elevated glutamate with its up-
regulated receptor NMDA1 in nerve fibers, morphologically altered tenocytes
and blood vessels44. This suggests an increased excitability of nerves, vessels and
tenocytes. Interestingly, none of the controls exhibited a neuronal co-existence
of glutamate and NMDAR1 in contrast to prominent neuronal occurrence in all
the painful tendons, which may reflect an important pain regulatory mechanism
in tendinopathy.
Summary
In summary, external forces, to which the skeletal tissues are subjected, will be
transduced through the peripheral nervous system and its messengers to tissue
adaptive changes – either physiological or pathological. The neuronal system
represents an important aspect of tendon pathology as well as an opening for
specific time-dependent and localized therapeutic interventions.
16
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tendon fibroblasts increases the production of prostaglandin E2 and levels of cyclooxygenase
expression: a novel in vitro model study. Connect Tissue Res 2003;44:128-33.
58. Woo SL, Gomez MA, Woo YK, Akeson WH. Mechanical properties of tendons and ligaments. II.
The relationships of immobilization and exercise on tissue remodeling. Biorheology 1982;19:397-408.
59. Yaraee R, Ghazanfari T. Substance P potentiates TGFbeta-1 production in lung epithelial cell lines.
Iran J Allergy Asthma Immunol 2009;8:19-24.
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augmented by injury and mediated by different alpha1-adrenoceptor subtypes. Circulation research
2001;89:815-22.
17
10
Biomechanics of the Achilles Tendon
“The journey is the reward”
(Confucius)
Chapter 4.
Biomechanics of the
Achilles Tendon
Claudio Rosso, Victor Valderrabano
Take Home Message
• The Achilles tendon has to be seen and studied in conjunction with its muscles
and its aponeurosis as a so-called muscle-tendon unit (MTU).
• In running, the Achilles tendon acts like a spring. In this way, the calf muscles can
work at their optimum length.
• Biomechanical reasons to develop Achilles tendinopathy may be intrinsic or ex
trinsic but are predominantly a combination of both.
Introduction
As recreational sports activities are getting more and more popular and
athletes are being pushed to enhance their performance, injuries in sports are
increasing7,26. As tendons transmit muscular forces to the bone, injuries of the
muscle-tendon unit (MTU) are especially frequent43. The Achilles tendon (AT),
the strongest tendon of the human body, is thus at great risk of injury40. Achilles
tendon disorders can most easily be divided into acute or chronic. Acute disorders
are for instance AT rupture. Chronic disorders are Achilles tendinopathy21,52. The
rising incidence of Achilles tendinopathy is not only seen in athletes but also in the
sedentary population1,31. Achilles tendinopathy is relatively common in runners,
11
track and field and racquet athletes as well as soccer and volleyball players55.
Mechanical loads of the AT are immense thus biomechanical considerations are
important, especially in Achilles tendinopathy.
Biomechanics of the healthy Achilles tendon - Properties of the Achilles

tendon
Functional muscle-tendon unit (MTU)

In the past decade, tendons have not been studied in isolation but in conjunction
with their aponeurosis and muscle as one functional muscle-tendon unit
(MTU)12,36. As the MTU forms a biomechanical unit, it is difficult to account for the
contribution to movement, force and force transfer of the tendon itself.
Visco-elastic / spring-alike properties

Tendons per se exhibit visco-elastic properties akin to a spring10,36,48. This gives
the tendon the ability to store energy and to release energy at a later time,
especially in running36. As a spring, during the stance phase of gait, energy is
being absorbed by the tendon and released at the push-off phase. In one-
legged hopping, 74% of the mechanical energy is stored and 16% of the total
mechanical energy of the hop arises from this elastic recoil of the AT27. During
normal walking, this accounts for 6% of the total mechanical energy34.
Catapult action
There are also additional considerations in normal gait and running, as they differ
in ground contact time. Contact time during human walking does not match the
cycle time of the resonant frequency of the elastic MTU-component of 2.6-4.3
Hz, corresponding to a ground contact time of 233 to 385 ms. Compared to that,
ground contact time of normal gait is 640 ± 50 ms which is much longer than
the one of the resonant elastic frequency2,19. This leads to the concept of catapult
action, in which elastic energy is not provided directly from initial negative work
but from muscle action. In running (increasing speed and frequency, decreasing
ground contact time), the spring-like properties become increasingly important
(Figure 1).
12
Behaviour
Catapult Properties
Spring Properties
Increasing Speed
Figure 1: Spring-versus-catapult properties.
With increasing speed in gait (from walking to running), the spring-alike property
of the tendon is increasingly important, and the catapult-action properties are
less important.
Fenn effect and force-velocity relationship

The goal of an optimal cooperation between muscles and tendons in the MTU is
to consume less energy. Tendons help muscles consume less energy, especially
in high demand actions such as running. Muscle fibres have two important
properties in this context: Firstly the Fenn effect (Fenn, 1924)9: if muscles work
at higher shortening velocities, they produce more energy. As tendons act in a
spring- or catapult-like fashion, velocities of muscle contractions can be reduced,
therefore saving energy. Secondly, the force-velocity relationship states that the
amount of force produced decreases with increasing shortening velocity (Hill,
1938)16. The tendons take over the “fast” part of this action, and thus muscles can
work close to their optimal force-velocity relationship.
As the AT is not a rigid organ but acts as a spring also by means of length, muscles
work almost isometrically, and consequently the whole mechanism of energy
storage is also energy saving as muscles can work at their optimum length10,28,48.
Force-length and stress-strain relationship

About 30 years ago, the force-length relationship was studied thoroughly6. With
increasing force, tendons lengthen to a certain degree. From this point onwards,
the liaison between force and length is not convenient anymore and results in
failure (Figure 2).
13
Figure 2: Force-Length Relationship.
Loading of the tendon is initially followed by only little gain in length (ascending
limb). Later point, the production of slightly greater force results in lengthening
(plateau region). The descending limb is referred to as failure of the tendon.
The stress-strain curve of tendons (Figure 3) reveals the intrinsic material

properties rather than macroscopic properties of the tendon. In both curves, four
regions can be distinguished. In Region I, the tendon crimp angle of its collagen
fibres is being stretched, and the fibres are being aligned (toe region). In Region
II, loading causes linear lengthening of the tendon until the end point in which
fibres begin to break (linear region). In Regions III and IV, the tendon begins to
fail (failure region). Initially (Region III), additional fibre ruptures take place. With
further loading, the tendon will completely fail. Elongation and strain of about
10% result in complete failure (Region IV)34.
Figure 3: Stress-Strain Curve.
With increasing stress (y-axis) the tendon toes in the beginning (yellow),
afterwards the strain of the tendon is linear to increasing stress (orange). The
elastic component of the tendon is then exhausted, and failure and consequently
14
rupture occur (green). The white line indicates mechanical hysteresis in unloading
of the tendon (see below).
Hysteresis
Another important property of healthy tendons is mechanical hysteresis.
Stretching of the tendon has been discussed before. If the loading of the tendon
is reduced, the tendon does not return to its initial state in the same way (on the
same line on the curve) but to a slower degree (white line in Figure 3). In vitro
tests revealed a value of mechanical hysteresis of about 10%42.
Conditioning
A mechanical hysteresis of about 10% is only obtained after the tendon has
been conditioned, i.e. it has undergone a few stretch-recoil cycles. After a
prolonged period of rest, the tendon needs to be stretched to be ready for force
transmission32. To obtain reproducible data, tendons require pre-conditioning
by repeated loading and recoiling47. This history dependency has significant
physiological implications with the stress-strain curve (Figure 3) shifting to the
right and thus making the tendon more resistant to stress. This phenomenon can
also be regarded as a working “steady state” of the tendon. At first, it has been
considered as an artefact but recent studies have shown that conditioning also
takes place in vivo23,34.
Biomechanics of the altered Achilles tendon
Overuse injuries commonly have a multifactoral origin. Intrinsic and extrinsic

factors interact with each other. Two-thirds of Achilles tendon disorders arise
from changed intrinsic factors51. We will give an insight into the effects of intrinsic
and extrinsic factors in Achilles tendinopathy.
Biomechanical causes of tendinopathy
Insertional tendinopathy of the Achilles tendon
Enthesiopathies such as Achilles insertional tendinopathy (AIT) have to be

differentiated from mid-portion Achilles tendinopathies. The enthesis organ
concept of Rufai et al. focuses on the junction between the tendon and the bone
such as in jumper’s knee, tennis or golfer’s elbow, and AIT50. The junction area is
exposed to shear strains as fibres do not enter the bone perpendicular33. Causes
of Achilles insertional enthesiopathy can be:
- Muscle fatigue by altering muscle-tendon stiffness17.
- Training on hard surfaces by absorption of shock waves and consequently
focus of stress on the junction as bone being stiffer than the muscle-tendon
unit39.
- Dysbalance and/or insufficiency of the gastrocnemius, soleus and tibialis
15
anterior muscles with the result of poor control of foot pronation during
landing by changing the alignment of the calcaneus37.
- Stress-shielding (see below).
Stress- or strain-shielding is an important factor in AIT. Lyman et al. have shown

that the posterior sites of the AT are exposed to significantly more strain as the
anterior sites with movement into dorsiflexion of the ankle29. As the anterior
portion of the AT is more frequently involved in AIT and the posterior sites are
exposed to more strain, the theory of stress-shielding is supported.
Mid-portion tendinopathy
Among Achilles tendon overuse injuries, mid-portion Achilles tendinopathy is
the most common entity20. In mid-portion Achilles tendinopathy, causes can be
divided into intrinsic and extrinsic factors but most commonly the interaction of
both can be seen51.
As an intrinsic factor, the collagen fibers spiral up to 90° between the muscle and
the calcaneus. This produces an area of intense stress48, which may be a factor
of avascularity and thus a factor of tendon disorders54. Malalignment such as
varus/valgus deformities or lateral ankle instability impose excessive strain on
the AT through the so-called ligamentum anulare as a thickening of the body
facia around the AT. Hyperpronation seems related to Achilles tendinopathy51.
Imbalance of the agonist-antagonist muscle action51, poor running style11, age30,
insufficient warm-up and stretching before sports5 are other contributing factors
to Achilles tendinopathy. Another important intrinsic factor may be chronic
eccentric loading of the AT with the foot in dorsiflexion, when the tendon does
not work at its optimal length as in volleyball players.
Extrinsic factors often contribute to already impaired intrinsic factors. The
quality of the footgear is a problem in runners. Footgear with its changing heel
padding may modify the lever-arm and the spring properties of the shoe itself53.
Additionally, old footgear may change the varus-/valgus alignment. In this way,
the biomechanics of the whole AT is changed. Environmental circumstances
such as ground surface influence ankle statics, and consequently Achilles
tendon strain force. Excessive increase in sporting activity is another risk factor
for Achilles tendinopathy49. All athletes with repetitive mechanical loadings are
at danger of developing (Achilles) tendinopathy3.
Biochemical changes in tendinopathy
The source of pain in Achilles tendinopathy is still unknown. Given the known
mast-cell activity, recently it was supposed that neural-mast cell interaction
may lead to discharge of mast-cell components that could modulate pain15.
In tendinopathy, (a) collagen content was subnormal, (b) water content was
increased, (c) relatively young collagenous matrix was present (low pentosidine),
(d) hydroxylated lysine residues were present, (e) matrix metalloproteinase
activity was increased, and (f ) collagen type I and III gene expression was
16
upregulated8.
Effects of aging and disuse
Disuse is closely connected to aging; a disused tendon has similar changes as

an aged tendon21. Substantial changes are seen in vivo by ultrasound in both
ageing and disuse: tendon stiffness diminishes44. This is at least partly because of:
- Decreased collagen turnover and packing density38.
- Increased collagen crimp angle41.
- Decreased water content18.
In vitro aged tendons show:

- Increased: (I) collagen cross-linking, (II) increased elastin, (III) increase in type V
collagen.
- Decreased: (I) collagen crimp angle, (II) decreased extracellular water and
mucopolysacharide content22.
In summary, the aged tendon loses its elastic properties and increases in
viscosous properties with the result in a more compliant tendon.
The effects of a compliant tendon (decreased tendon stiffness) can be foreseen36;
muscles will not be able to operate at their optimum length and shortening
velocities, consequently the muscle has to work more. With increasing muscle
work, heat will therefore increase, and may reach temperatures up to 42.5°C
in vivo, with subsequent cumulative tendon damage. Acting as elastic energy
stores, degenerative lesions are often observed in the core of tendons. A
compliant tendon makes proprioception more difficult.
With the Achilles tendon, also the ankle and surrounding structures age.
Osteoarthrotic changes in the ankle may lead to malalignement and reduced
ankle movement and thus changes in the AT-biomechanics.
Altered mechanical loading and training
Human tendons are metabolically active, and hence reacting to chronic loading25.
In vivo, the Achilles tendon becomes stiffer with continual mechanical loading
and more compliant with less mechanical loading. One explanation would be
that the cross-sectional area is increasing but alteration of the Young’s modulus
indicates that there may also be changes in material composition of the tendon22.
In chronic loading, synthesis and degradation are increased. Degradation has
been shown in the initial phase of increased chronic loading but is followed
by a dramatic increase of synthesis in the following days24. Chronic loading
increases glucose uptake in tendons13. Moreover, cross-links, proteoglycans and
glycosaminoglycans seem to be influenced22. Whether resistance or endurance
training alter the cross-sectional area is still subject to research. Resistance
training appears to increase tendon stiffness by up to 65% with unchanged
tendon dimensions, and produces up to 22% decrease of mechanical hysteresis44.
17
On the other hand, habitual long distance running (> 5 years) is shown to enlarge
the cross-sectional area by 22% compared to non-runners35. This could not be
shown for previously untrained runners after nine months14. The consequence
of increased cross-sectional area would be a reduction of stress per unit of the
tendon, consequently reducing the risk of rupture.
Summary and clinical implications
The Achilles tendon has to be seen and studied in conjunction with its muscles
(Mm. gastrocnemius medialis et lateralis and M. soleus) and its aponeurosis as a
so-called muscle-tendon unit (MTU).
In running, the Achilles tendon acts like a spring. In this way, the calf muscles can
work at their optimum length thus enhancing force output.
As other tendons, the Achilles tendon has an optimum work level which is
described by the stress-strain curve. Mechanical hysteresis and conditioning
have to be considered in Achilles tendon biomechanics.
Biomechanical reasons to develop Achilles tendinopathy may be intrinsic or
extrinsic but are predominantly a combination of both. Intrinsic factors are: up to
90° twisting of collagen fibres in the course of the AT, avascularity, malalignement,
hyperpronation, dysbalance of the agonist-antagonist muscle action, poor
running style, insufficient warm-up and stretching before sports, age, eccentric
loading of the AT with the foot in dorsiflexion.
Quality of the footgear with changing lever-arm and spring properties, old
footgear by changing alignment, environmental circumstances such as ground
surface, excessive increase in sporting activity, repetitive mechanical loadings
are extrinsic risk factors for developing (Achilles) tendinopathy.
Aging and disuse will lead the visco-elastic tendon to lose its stiffness (decreased
elastic properties, increased viscous properties), thus becoming more compliant
and consequently decreasing visco-elastic output.
Training may lead to stronger and stiffer tendons enhancing the spring-like effect.
Resistance loading can diminish or even reverse aging and disuse alterations44-46.
As a well-balanced agonist and antagonist might reduce the chance of developing
tendinopathy and injuries, muscle balance and proprioceptive training may
lessen the risk of tendinopathy4.
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16
Diagnosis
“Diagnosis is not the end, but the

beginning of practice.”
(Martin H. Fischer)
Chapter 5.
Diagnosis
Karin G. Silbernagel, Maayke N. van Sterkenburg, Jón Karlsson
Take Home Message
• Thorough history taking and clinical examination are essential in diagnosing

Achilles tendinopathy.
• Clinically, a distinction between midportion (2-6 cm proximal to tendon inser
tion) and distal (insertion to the calcaneus) Achilles tendinopathy can be made
on the basis of the location of the pain in the area.
Introduction
Achilles tendinopathy is the clinical diagnosis for a syndrome characterized by a

combination of pain, swelling (diffuse or localized), and impaired performance
of the Achilles tendon16. Clinically, a distinction between midportion (2-6 cm
proximal to tendon insertion) and distal (insertion to the calcaneus) Achilles
tendinopathy can be made on the basis of the location of the pain in the area. It
should also include the histopathological entities peritendinitis and tendinosis16,
since in most patients, there is a combination of tendinopathy of the main body
of the Achilles tendon and a paratendinopathy, and differentiation is confusing26.
17
Clinical assessment
Midportion Achilles tendinopathy

Midportion Achilles tendinopathy accounts for 55-65% of all the Achilles tendon
injuries7, 12. Collecting an accurate history is essential, and the onset of symptoms,
injury mechanism, possible previous Achilles tendon injuries and what makes
the symptoms better or worse should be carefully documented. It should be
remembered that 2% of Achilles tendon injuries can be due to systemic diseases,
such as rheumatoid arthritis or other inflammatory joint diseases8. Their presence
should be excluded.
Patients usually describe gradual onset of pain. However, they occasionally report
a single incident that started the symptoms. Many patients have experienced
pain for months or intermittently for many years. Initially, symptoms occur after
heavy physical activity, but as the injury progresses some patients develop pain
during physical activity. Sometimes patients also have pain in combination with
daily activities, such as walking. Patients describe tendon stiffness in the morning
and/or after sitting for longer periods of time. The main complaint is pain with
activity, but, in some severe cases, the patients also report pain at night. In
the literature, there are commonly reports of a correlation between pain level,
morning stiffness and severity of disease9, 20, 25.
Distal Achilles tendinopathy

Approximately 20-25% of all Achilles tendon injuries is reported to be distal and is
also called insertional Achilles tendinopathy 7, 12. In an epidemiological study over
a ten-year period in patients with Achilles tendon injury, 23% had distal pain and,
of these, 61% were diagnosed as insertional tendinopathy, 21% as retrocalcaneal
bursitis and 18% as both13.
These patients report the same complaints as in midportion injury and/or pain
related to the type of shoe/athletic wear. In this case, the pain can occur due
to external compression on the tendon insertion. Swelling around the Achilles
tendon insertion to the calcaneus, with redness and warmth, could also be present
and might be related to active bursitis. The patients sometimes also report pain
after running uphill, standing on a ladder, or walking barefoot on sand. Clinically,
there is pain when the tendon insertion is palpated and there is often also pain
slightly more medially or laterally from bursitis. A retrocalcaneal bursitis is caused
by repetitive impingement of the bursa between the calcaneus and the Achilles
tendon from overuse or a posterosuperior calcaneal prominence.
Physical examination
Palpation
On physical examination, the patients report pain on palpation in the midportion
of the tendon (2-6 cm proximal to the tendon insertion). Sometimes there is a
palpable thickening, usually in more chronic stages. Noticeable crepitation can
be indicative of adhesions of the paratenon and paratendinopathy in more acute
16
Diagnosis
stages. The documentation of any nodular swelling, crepitation, warmth, redness

and level of pain with palpation are recommended, and clinically relevant. Cook
and co-workers found good reliability for palpation in patients with patellar
tendinopathy, however, they also reported that tenderness on palpation can
occur in patients without tendinopathy4.
Two additional clinical tests have been reported in the literature. The Royal
London Hospital test differentiates between isolated tendinopathy of the tendon
proper and involvement of the peritendineum. The thickening is palpated,
and the patient is then asked to dorsi- and plantarflex the ankle. If the nodule
moves, this is an indication that it is situated within the tendon proper. If it does
not, the peritendineum is most likely involved. The painful arc sign describes a
painful nodule on palpation with the ankle in a neutral position. On dorsi- and
plantarflexion, palpation of the same location is no longer painful. These tests
have been validated in one study15.
Foot morphology
An evaluation of standing posture, balance and anatomical malalignments is
usually performed during clinical examination. There are various techniques for
evaluating the subtalar varus and forefoot varus as measures of varus alignments
that would cause functional hyperpronation during walking and running.
Clinically, measurements are often done in a non-weight bearing position,
using a goniometer or in a weight bearing position describing the foot as cavus,
neutral or pronated10, 13. Clinical classification of a high, normal and low arch
can also be done, but this is mostly a subjective measure by the evaluator with
possible clinical benefits regarding decision-making if there is a need for custom-
made orthotics. Motion analysis systems and force plates have also been used to
evaluate foot morphology in studies relating to Achilles tendinopathy10, 14. Their
use in clinical practice is, however, not widespread.
Range of motion
Measurements of ankle range of motion are usually performed in a clinical setting,
but also in research studies. The literature reports that Achilles tendinopathy
is related to both decreased and increased range of motion. Measurement
techniques vary from goniometric evaluations to measurements with passive
motion in a hydraulic isokinetic dynamometer6, 10, 17. Goniometric measurements
can be performed with the patient supine or standing, and both passively or
actively with the foot carefully put in a subtalar neutral position. The arms of
the goniometer should be aligned, with the proximal arm along the midline of
the fibula, the fulcrum at the lateral malleolus, and the distal arm parallel to the
fifth metatarsal19. Regular goniometric range of motion evaluations reliable, with
intra-tester reliability being higher than inter-tester reliability3, 24.
17
Muscular hypotrophy
Circumference measurements are often used in the clinical setting to determine
gross muscular atrophy, but they cannot be used to determine muscle quality.
Circumference measurements are affected by swelling, and body composition (fat
versus muscle) and increases in circumference may not indicate increased muscle
mass or vice versa. Techniques include documenting maximum circumference or
measuring at predetermined positions relating to bony landmarks21, with good
reliability for maximum calf circumference measurements (ICC 0.97)18.
Imaging methods
The imaging modalities that are primarily used in patients with Achilles
tendinopathy are ultrasonography (US) and/or magnetic resonance imaging
(MRI)2, 9, 20. Conventional radiographs are described as being useful in evaluating
possible bony abnormalities distally, such as Haglund’s deformity9, 27. Imaging
is useful for documenting tendon changes, and out other causes of patients’
symptoms2, 9, 20, 28, 29.
US is quick, safe and inexpensive, but it is regarded as user dependent and
requires an experienced radiologist25. US is valuable to detect the occurrence
and location of tendon lesions, but it is unable to differentiate between partial
tendon ruptures and focal degenerative areas22, 30. Sometimes, mild to moderate
changes can be found in both symptomatic and asymptomatic tendons, and the
changes seen are not always related to patients’ symptoms5, 22, 23. In a prospective
study of the value of US and MRI in Achilles tendon disorders, US identified
abnormal morphology in 37 of 57 symptomatic tendons (65%) and normal
morphology in 19 of 28 asymptomatic tendons (68%)11. Furthermore, baseline
US findings did not predict the 12-month clinical outcome. Some correlation
between the severity of US findings and predictions of recovery has been shown
in a retrospective study1. Abnormalities seen on US in asymptomatic Achilles
tendons were related to a 45% risk of developing symptoms5. More recently, US
with color Doppler has been used to locate areas of neovascularization in the
Achilles tendon31.
MRI is less user-dependent, and is regarded as good at visualizing pathological
conditions of the tendon and peritendinous structures9, 20, 25. Since a surgeon
is generally not well-trained at interpreting US-images, MRI and especially its
three dimensional element is valuable for pre-operative planning. Shalabi and
co-workers28, 29 have also used MRI in the follow-up of patients with Achilles
tendinopathy treated with either surgery or exercise.
In their two-year prospective study of the value of US and MRI in assessments
of Achilles tendon disorders, Khan and co-workers11 found that MRI identified
abnormal morphology in 19 of 34 symptomatic tendons (56%) and normal
morphology in 15 of 16 asymptomatic tendons (94%). Lesser grades of MR
signal abnormalities at baseline were associated with better clinical status at the
12-month follow-up. They concluded that clinicians should exercise discretion
in ordering imaging tests and in interpreting their findings in chronic Achilles
tendon disorders, as both US and MRI commonly produce false positives and
16
Diagnosis
false negatives. Careful clinical correlation with imaging findings is essential.

Selective use of imaging in patients who fail to respond clinically and who may
have clinically underestimated tendon changes may be warranted. Although
our findings suggest that imaging adds little information of use for expert
sports medicine clinicians in diagnosing tendinopathy, it may be useful for
inexperienced clinicians who are unsure of their diagnoses and unfamiliar with
subjective outcome measures, and of course for preoperative planning.
References
1. Archambault JM, Wiley JP, Bray RC, Verhoef M, Wiseman DA, Elliott PD. Can sonography predict the
outcome in patients with achillodynia? J Clin Ultrasound. 1998;26:335-9.
2. Bleakney RR, White LM. Imaging of the Achilles tendon. Foot Ankle Clin. 2005;10:239-54.
3. Boone DC, Azen SP, Lin CM, Spence C, Baron C, Lee L. Reliability of goniometric measurements. Phys
Ther. 1978;58:1355-90.
4. Cook JL, Khan KM, Kiss ZS, Purdam CR, Griffiths L. Reproducibility and clinical utility of tendon
palpation to detect patellar tendinopathy in young basketball players. Victorian Institute of Sport
tendon study group. Br J Sports Med. 2001;35:65-9.
5. Fredberg U, Bolvig L. Significance of ultrasonographically detected asymptomatic tendinosis
in the patellar and achilles tendons of elite soccer players: a longitudinal study. Am J Sports Med.
2002;30:488-91.
6. Haglund-Akerlind Y, Eriksson E. Range of motion, muscle torque and training habits in runners with
and without Achilles tendon problems. Knee Surg Sports Traumatol Arthrosc. 1993;1:195-9.
Foot Ankle Clin. 2005;10:255-66.
8. Jarvinen TA, Kannus P, Paavola M, Jarvinen TL, Jozsa L, Jarvinen M. Achilles tendon injuries. Curr
Opin Rheumatol. 2001;13:150-5.
clinical management. Br J Sports Med. 2002;36:239-49.
10. Kaufman KR, Brodine SK, Shaffer RA, Johnson CW, Cullison TR. The effect of foot structure and
range of motion on musculoskeletal overuse injuries. Am J Sports Med. 1999;27:585-93.
11. Khan KM, Forster BB, Robinson J, Cheong Y, Louis L, Maclean L, et al. Are ultrasound and magnetic
resonance imaging of value in assessment of Achilles tendon disorders? A two year prospective
study. Br J Sports Med. 2003;37:149-53.
12. Kvist M. Achilles tendon injuries in athletes. Sports Med. 1994;18:173-201.
13. Kvist M. Achilles tendon injuries in athletes. Ann Chir Gynaecol. 1991;80:188-201.
14. Lowdon A, Bader DL, Mowat AG. The effect of heel pads on the treatment of Achilles tendinitis: a
double blind trial. Am J Sports Med. 1984;12:431-5.
15. Maffulli N, Kenward MG, Testa V, Capasso G, Regine R, King JB. Clinical diagnosis of Achilles
tendinopathy with tendinosis. Clin J Sport Med. 2003;13:11-5.
16. Maffulli N, Khan KM, Puddu G. Overuse tendon conditions: time to change a confusing terminology.
Arthroscopy. 1998;14:840-3.
17. Mahieu NN, Witvrouw E, Stevens V, Van Tiggelen D, Roget P. Intrinsic Risk Factors for the
Development of Achilles Tendon Overuse Injury: A Prospective Study. Am J Sports Med. 2006;34:226-
35.
18. Moller M, Lind K, Styf J, Karlsson J. The reliability of isokinetic testing of the ankle joint and a
heelraise test for endurance. Knee Surg Sports Traumatol Arthrosc. 2005;13:60-71.
19. Norkin CC, White DJ. Measurement of joint motion: a guide to goniometry. Philadelphia:
Davis1985.
20. Paavola M, Kannus P, Jarvinen TA, Khan K, Jozsa L, Jarvinen M. Achilles tendinopathy. J Bone Joint
Surg Am. 2002;84:2062-76.
21. Paavola M, Kannus P, Orava S, Pasanen M, Jarvinen M. Surgical treatment for chronic Achilles
tendinopathy: a prospective seven month follow up study. Br J Sports Med. 2002;36:178-82.
22. Paavola M, Paakkala T, Kannus P, Jarvinen M. Ultrasonography in the differential diagnosis of
Achilles tendon injuries and related disorders. A comparison between pre-operative ultrasonography
17
and surgical findings. Acta Radiol. 1998;39:612-9.

23. Peers KH, Brys PP, Lysens RJ. Correlation between power Doppler ultrasonography and clinical
severity in Achilles tendinopathy. Int Orthop. 2003;27:180-3.
24. Rothstein JM, Miller PJ, Roettger RF. Goniometric reliability in a clinical setting. Elbow and knee
measurements. Phys Ther. 1983;63:1611-5.
25. Sandmeier R, Renstrom PA. Diagnosis and treatment of chronic tendon disorders in sports. Scand
J Med Sci Sports. 1997;7:96-106.
26. Saxena A. Surgery for chronic Achilles tendon problems. J Foot Ankle Surg. 1995;34:294-300.
27. Schunck J, Jerosch J. Operative treatment of Haglund’s syndrome. Basic, indications, procedure,
surgical techniques, results and problems. Foot and Ankle Surgery. 2005;11:123-30.
28. Shalabi A, Kristoffersen-Wiberg M, Aspelin P, Movin T. MR evaluation of chronic Achilles tendinosis.
A longitudinal study of 15 patients preoperatively and two years postoperatively. Acta Radiol.
2001;42:269-76.
29. Shalabi A, Kristoffersen-Wilberg M, Svensson L, Aspelin P, Movin T. Eccentric training of the
gastrocnemius-soleus complex in chronic Achilles tendinopathy results in decreased tendon volume
and intratendinous signal as evaluated by MRI. Am J Sports Med. 2004;32:1286-96.
30. Astrom M, Gentz CF, Nilsson P, Rausing A, Sjoberg S, Westlin N. Imaging in chronic achilles
tendinopathy: a comparison of ultrasonography, magnetic resonance imaging and surgical findings
in 27 histologically verified cases. Skeletal Radiol. 1996;25:615-20.
31. Ohberg L, Lorentzon R, Alfredson H. Neovascularisation in Achilles tendons with painful tendinosis
but not in normal tendons: an ultrasonographic investigation. Knee Surg Sports Traumatol Arthrosc.
2001;9:233-8.
16
Imaging Techniques in Tendinopathy of the Achilles Tendon
“Failure is not an option”
(Attributed to Gene Kranz Apollo

13 Mission Director)
Chapter 6.
Imaging Techniques in
Tendinopathy of the
Achilles Tendon
Adam W. M. Mitchell, Justin C. Lee, Jeremiah C. Healy
Take Home Message
• Sonographic fusiform swelling, focal hypoechogenic areas and partial tears are
all prognostic factors and have an increased incidence with Achilles tendon
rupture.
• Neovascularisation relates to patient’s symptoms of pain, but appears to have
no long-term prognostic implication.
• Contrast enhanced MRI may be of greater value in the assessment of other
conditions which produce Achilles tendon pain, including paratendinopathy.
Introduction
A rupture of the Achilles tendon is easily diagnosed clinically. With the increasing
interest in the disorders of the Achilles tendon and the increase in specialised
imaging modalities, we are now aware of a number of further disorders
affecting the main body of the Achilles tendon, which include mid- substance
tendinopathy and paratendinopathy. Complex chronic trauma and/or partial
ruptures may hamper the clinical examination and the sensitivity of the clinical
diagnosis6.
Tendinopathy and paratendinopathy may also result in thickening of the heel,
17
and may not be accurately differentiated by clinical examination alone. Early

diagnosis is key to appropriate management.
The normal structure of tendons
Tendons comprise of cells (tenocytes) within collagen and ground substance,

predominantly ground substance. The collagen molecules are formed from
polypeptide chains and arranged in a triple helix pattern. With the aid of
proteoglycans crosslinks form between the molecules and are arranged in a
hierarchical manner. The fibrils are grouped to form fibres, bundles and fascicles.
The tendon is covered by epitenon, a loose connective tissue containing the
neurovascular supply. This superficial tissue has a lining known as the paratenon.
Typically tendons which course around bony surfaces and passing through
fascial slings tend to have a tendon sheath surrounded by synovium.
Collagen turnover is slow, between 50-100 days.
The origin of the Achilles tendon is where the posterior fascia of the triceps
surae unites with the fibres of the soleus muscle. The tendon inserts into the mid
portion of the posterior aspect of the os calcis.
Imaging modalities
Plain radiography has long been abandoned for assessing Achilles tendinopathy,
although it is still frequently performed in patients with heel pain. In most
patients, plain radiographs are relatively unrewarding other than demonstrating
calcification and possible other causes for heel pain, including bone trauma and
infection. Nuclear medicine studies, PET FDG studies and CT are all of limited
value. The mainstay of imaging of the Achilles tendon is ultrasound and MRI.
Ultrasound the Achilles tendon
A normal Achilles tendon demonstrates a homogeneous fibrillar structure

on the sagittal scans with approximately 6-8 characteristic undulating lines of
internal echos that reflect the acoustic borders between the collagen fibrils and
loose connective tissue between the fascicles4. Axial imaging demonstrates
the oval shape of the tendon, which has a superficial convexity and a deep
concavity (Figure 1). Occasionally, in some individuals the tendon is divided
by a hyperechogenic septum. The tendon is well demonstrated bordering
its subcutaneous fatty tissue by the paratenon, a visible hyperechogenic line
situated on the anterior and the posterior borders (Figure 2).
Anterior to the Achilles tendon lies the pretendinous fat pad (Kager’s triangle).
Along with the Achilles tendon, the fat pad fills the distal part of the triceps surae
compartment of the calf. This structure typically shows a mottled echo texture,
however, there is marked individual variability.
16
Figure 1: Axial sonographic image demonstrating normal appearance of the Achil-

les tendon (arrowheads) in cross-section.
Figure 2: Sagittal sonogram of the normal Achilles tendon (TA). The arrows point
out the echogenic paratenon lying on the anterior and posterior surfaces of the
tendon.
In one series, normal tendon thickness ranged from 4.0-6.7 mm (mean 5.2 mm)
in 24 subjects 4. In subjects with asymptomatic tendons, a sonographic thickness
of more than 6 mm was related to intensive sport suggesting physiological
adaptation to mechanical stress.
The sonographic findings of the insertion of the Achilles tendon are demonstrated
as a strong echogenic border against the bone (Figure 3). The tendon flattens
and covers the calcaneum. Interestingly, in children a broad layer of hyaline
17
cartilage covers the posterior aspect of the calcaneum, and using high-
resolution probes the structure of the hyaline cartilage can be demonstrated as
speckled hyperechogenic foci within relatively hypoechogenic matrix. Between
the Achilles tendon and the supero-posterior aspect of the calcaneum, a small
crescent-shaped bursa (retrocalcaneal bursa) may be demonstrated as a thin
hypoechogenic structure (Figure 3). The shape and position of this bursa will vary
depending on the degree of flexion and extension of the ankle).
Figure 3: Sagittal sonogram of the normal Achilles tendon insertion. TA=tendo

Achilles. The arrow points out the normal physiological retrocalcaneal bursa.
A frequent criticism is often related to the reproducibility of ultrasound findings.
Although ultrasound is operator-dependent, it is reproducible between individuals,
and serial observations are best performed by the same individual15.
Normal MRI of the Achilles tendon
Typical MRI findings of the Achilles tendon indicate a low signal homogeneous
structure on both T1 and T2 weighted images (Figure 4). Occasionally punctate
and short linear high foci are seen, especially on the anterior aspect of the
tendons in the axial series 11).
16
Figure 4: Sagittal T1-weighted MRI of the normal Achilles tendon. FHL = flexor
hallucis longus muscle, S = soleus, K = Kager’s fat pad, short arrows demonstrate
posterior margin of the Achilles tendon.
The plantaris tendon may be visible as a linear structure passing through the
medial distal portion of the pre-Achilles fat pad. The plantaris arises from the
lower part of the lateral supracondylar line and has a small fusiform belly which
forms a long slender tendon which obliquely crosses the calf between the
gastrocnemius and the soleus and inserts onto the calcaneum medial to the
Achilles tendon (Figure 5). This may be absent in 10% of patients. Occasionally,
the tendon may blend into the medial fibres of the Achilles in the lower third of
the calf.
17
Figure 5: Axial T2-weighted MRI demonstrating position of the plantaris tendon

within Kager’s fat pad (K) anteromedial to the Achilles tendon (TA).
The use of intravenous gadolinium demonstrates the normal enhancing

synovium in the bursa. The tendon and the paratendon do not enhance in normal
individuals, and enhancement may be demonstrated around the paratenon on
pathological states. Further developments using ultrashort TE (UTE) in higher
field strength MRI scanners can produce signal from the tendon in orthogonal
planes21.
16
Sonographic findings
Excluding the paratenon, there are four typical sonographic findings in patients
with clinical Achilles signs and symptoms. Sonographic findings include normal
tendons, enlarged tendons (spindleshape/fusiform thickening), hypoechoic
and hyperechogenic lesions within the tendons, and power Doppler imaging
neovascularisation (Figure 6).
Figure 6A: Sagittal sonogram demonstrating diffuse fusiform swelling of the Achil-
les tendon.
Figure 6B: Sagittal Power Doppler sonogram of chronic non-insertional Achilles

tendinopathy. Note the colour inside the tendon indicating the presence of neoves-
sels. The inhomogenous structure of the tendon with hypo- and hyperechogenic
transformations are also apparent.
17
Figure 6C: Sagittal sonogram demonstrating focal tendinopathy (arrowheads)

principally affecting the posterior surface of the Achilles tendon. The long arrows
demonstrate the anterior margin of the slightly expanded Achilles tendon. The
paratenon is thickened dorsally.
In patients with a clinical diagnosis of Achilles tendinopathy, Archambault et al.

demonstrated statistical significance in poor recovery time between tendons
with normal appearance, enlarged tendons, and tendons with hypoechoic
lesions1. Furthermore, patients without sonographic changes had significantly
better clinical outcome after conservative treatment15. Moreover, patients with
tendon thickening and circumscribed lesions had higher rates of spontaneous
tendon rupture.
Achilles tendinopathy typically affects the middle third of the Achilles tendon.
Gibbon et al demonstrated that small micro-tears, indicative of a tendinopathic
process were present in approximately 28% of normal individuals5. Conversely,
only 18% of athletes with chronic Achilles tendinopathy did not show
ultrasonographic evidence of intra-tendinous disruption. Patients with a partial
tendon rupture all had micro-tears in the middle third of the Achilles tendon.
The increased frequency of micro-tears was significantly associated with Achilles
tendon rupture.
A more recent study performed by Leung et al.9 concluded that Achilles

tendinopathy results in enlargement and more particularly in the mid and distal
portions of the tendon with disruption of the normal intratendinous fibrillar
pattern and an associated increase in tendon vascularity. Additional signs were
increased Karger’s fat pad echogenicity and paratenon thickening. Tendon
calcification and changes in the retrocalcaneal bursa and calcaneal contour were
not specific for Achilles tendinopathy.
Over the last ten years, there has been increasing interest in neovascularisation
of Achilles tendon, and a number of studies assessed the usefulness of this
16
technique17,22. Neovascularisation is specific for patient’s pain, but it does not

indicate an unfavourable outcome, although tendon inhomegeneity does.
Furthermore, power Doppler imaging demonstrates significantly greater
microvascularity than colour Doppler imaging. All neovascularity appears to
arise from the ventral side of the Achilles tendon, with a non-linear relationship
between tendinopathy, tendon size and microvascularity. However, there is a
direct relationship between the power Doppler imaging and the duration of
symptoms. Moreover, it was unlikely that neovascularisation occurred in tendons
smaller than 6 mm.
Symptoms of Achilles tendinopathy may be indistinguishable from those
of paratendinopathy. The typical findings are a normal Achilles tendon with
circumferential hypoechogenic halo around the tendon (Figure 7), often
combined with an (echogenic) thickening of the paratenon. Power Doppler
imaging may reveal hypervascularity. Ultrasound is superseded by contrast
enhanced MRI for the detection of Achilles paratendinopathy. Not infrequently,
Achilles tendinopathy and paratendinopathy co-exist.
Figure 7: Axial sonogram demonstrating a thickened hypoechoic paratenon (arrow-

heads) covering the medial side of a normal Achilles tendon (TA).
MRI and Achilles tendon abnormalities
Over the last decade, MRI has proved an extremely sensitive and specific
technique for assessing the Achilles tendon and tendon abnormalities (Figure 8).
17
Figure 8: Sagittal T1 MRI demonstrating fusiform expansion of the Achilles tendin-

opathy consistent with chronic tendinopathy.
Figure 9A. Sagittal and B. Axial fat-

saturated T1-weighted MRI following
IV gadolinium demonstrating features
of chronic non-insertional Achilles
tendinopathy and paratendonopathy.
The Achilles tendon demonstrates
fusiform expansion (arrowheads).
Central enhancement is seen within
the tendon (curved arrow) consistent
with intratendinous neovasculariza-
tion. Posterior peripheral enhance-
ment indicates associated paratendo-
nopathy (long arrows).
16
The overall sensitivity of MRI was 94%, with a specificity of 81% and a positive
predicted value of 90% for Achilles tendon abnormalities9. With more refined
imaging sequences and 3 Tesla imaging sensitivity and specificity are likely
to improve. Furthermore, in as many as 68% of patients in that study with an
associated intratendinous lesion also had evidence of paratendinopathy, a
finding supporting earlier work19.
The role of ultrasound and magnetic resonance imaging
Thickening of the Achilles tendon can be easily demonstrated in both MR and

ultrasound22. MR was initially shown to be superior in the detection of incomplete
tendon rupture and evaluation of the various stages of chronic degenerate
changes. From this study, Neuhold et al. recommended that if ultrasound
remains unclear, it would be appropriate to proceed to MRI. However, a further
study17 indicated that, in patients with Achilles tendon disease, power Doppler
imaging demonstrated proliferation of vessels in enlarged abnormal tendons in
the absence of definite tears. Importantly, the neovascularisation could not be
fully assessed on MR scanning.
Aström et al.2 suggested that both ultrasound and MRI gave similar information in
patients with chronic achilles tendinopathy, partial ruptures and tears. Although
these findings are important, the technological progress in ultrasound probes
and software and refinement in MRI technology may confound the perceived
wisdom.
A further study performed by Khan et al.8 demonstrated only moderate correlation

between ultrasound and MR findings in chronic Achilles tendinopathy. They also
suggested that graded MR appearance was associated with clinical outcome
however ultrasound was not.
Overall strategy
Achilles tendinopathy mimics

Clinical assessment of achillodynia remains difficult and there are a number of
conditions that can produce identical symptoms. These need to be diagnosed
accurately, as management and prognosis are determined by the pathological
process.
Typical conditions which produce achillodynia include plantaris rupture,
calcifictendinopathy, fat pad impingement, paratendinopathy, accessory
muscles (soleus) and inflammatory conditions (Figure 10). Further assessment of
the musculotendinous junction and the tendinosseous junctions is mandatory.
17
Figure 10: Extended-field-of-view sonogram of the calf demonstrating the presence

of an accessory soleus posterior to the flexor hallucis longus (FHL) inserting on the
posteromedial os calcis.
Conditions relating to the ankle joint can also mimic Achilles tendon pain
and include posteromedial and posterior impingement at the talotibial joint,
posterior subtalar joint abnormalities and os trigonum syndrome (Figure 11).
Figure 11: Sagittal fat-saturated T1 post-IV gadolinium demonstrating posterior

ankle impingement. Note the large os trigonum (curved arrow) associated with
enhancement of the posterior synovial recess of the ankle.
16
Overall imaging strategy
Ultrasound is probably the most accessible tool for assessing the Achilles
tendon, and, with smaller higher resolution machines, can be performed as an
‘office’ test. Importantly, ultrasound performs two specific functions. The first is
to exclude some of the other potential causes and mimics of Achillodynia. The
second confirms paratendinopathy, fusiform tendon swelling, focal areas of
hypoechogenicity and neovascularisation. Neovascularisation is associated with
pain, and the reduction of new vessels may be important in the long-term follow
up and prognosis of patients.
The role of MRI remains important not only in assessment of the hindfoot but
also to establish the diagnosis of Achilles tendinopathy. Importantly, both MRI
(including contrast MRI) and ultrasound have important roles in the assessment
of achillodynia.
References
1. Archambault JM, Wiley J P, Bray RC, Verhoef M, Wiseman DA, Elliot PD. Can sonography predict the
outcome in patients with Achillodynia? J Clin Ultrasound 1998;26:335-9.
tendinopathy: a comparison of ultrasonography, magnetic imaging and surgical findings in 27
histologically verified cases. Skeletal Radiol.1996;27:615-20.
3. Bydder et al. The magic angle effect: a source of artefact, determinant of image contrast, and
technique for imaging. J Magn reson imaging. 2007;25:290-300.
4.Franz M, Kainberger F, Engl A, Barton P, Huebsch P, Neuhold A, Salomonowitz E, Injury of the
Achilles Tendon: Diagnosis with Sonography. AJR 1990;155:1031-6.
5. Gibbon WW, Cooper JR, Radcliffe GF. Sonographic incidence of tendon micro-tears in athletes
with chronic Achilles tendinosis. Br J Sports Med. 1999;33:129-30.
6. Ingliss AE, Scott WN, Sculco TP, Patterson AH. Ruptures of the Tendoachilles. J Bone Joint Surg
(Am) 1976;58:990-3.
7. Karjalainen P, Soila K, Aronen H et al. MR imaging of overuse injuries of the Achilles tendon. AJR
2000;175:251-60.
8. Khan KN, Forster PB, Robinson J et al. Are ultrasound and magnetic resonance imaging of value in
assessment of Achilles tendon disorders: a two year prospective study. British BRJ Sports Med.
2003;37:149-53.
9. Leung JL, Griffiths JF. Sonography of chronic Achilles tendinopathy: a case control study. J Clin
Ultrasound. 2008;36:27-32.
10. Mafulli N, Binfield PM, Moore D, King JB. Surgical decompression of chronic central core lesions
of the Achilles tendon. Am J Sports Med 1999;27:747-52.
11. Mantel D, Flautre B, Bastian D, Delforge PM, Delvalle A, Leclet H. Structural MRI study of the
Achilles tendon: correlation with microanatomy and histology. Journal de Radiologic 1996;77:261-5.
12. Moven T, Gad A, Reinholt PF, Rolfe C. Tendon pathology in longstanding Achillodynia: biopsy
findings in 40 patients. Acta Orthop Scand 1997;68:170-5.
13. Nehrer S, Breitenseher M, Brodner W et al. Clinical and sonographic evaluation of the risk of
rupture in the Achilles tendon. Arch Orthop Trauma Surg 1997;116;14-8.
14. Neuhold A, Stiskel M, Kainberger F et al. Degerate Achilles tendon disease: assessment by
magnetic resonance and ultrasonography. Eur J Radiol. 1992;14:213-20.
15. O’Connor et al. Ultrasound assessment of tendons in asymptomatic volunteers: a study of
reproducibility. Eur radiol. 2004;14:1968-73.
16. Richards PJ, Dheer AK, McCall IM . Achilles tendon size and power Doppler ultrasound changes
compared to MRI: a preliminary observational study. Clin Radiol 2001;56:843-50.
17. Richards PJ, Win T, Jones PW. The distribution of microvascular response in Achilles tendinopathy
assessed by colour and power Doppler. Skeletal Radiol. 2005;34:336-42.
17
18. Rolfe C, Movin T. Etiolology, histopathology and outcome of surgery in Achillodynia. Foot Ankle
Int 1997;18:565-9.
19. Schepsis AA, Wagner C, Leech RE. Surgical management of Achilles tendon overuse injuries: A
long term follow up study. Am J Sports Med 1994;22:611-9.
20. Talon C, Colman BD, Khan KN, Maffulli N. Outcome of surgery for chronic Achilles tendinopathy:
a critical review. Am J Sports Med 2001;29:315-20.
21. Tyler et al. Magnetic resonance imaging with UTE pulse sequences: technical considerations. J
Magn Reson Imaging. 2004;25;279-89.
22. Zanetti M, Metzdorf A, Kundert H et al. Achilles tendons: clinical relevance of neovascularisation
diagnosed with power Doppler ultrasound. Radiol 2003;227:556-60.
16
Paratendinopathy
“Assumptions allow the best in life

to pass you by’ ”
(John Sales)
Chapter 7.
Paratendinopathy
Maayke N. van Sterkenburg, Mikaa Paavola, C. Niek van Dijk
Take Home Message
• The etiology, pathogenesis and natural course of Achilles tendinopathy are

largely unknown.
• It is questionable whether the tendon itself causes complaints, since
several studies have been published on asymptomatic degenerative changes
inside the tendon.
• More emphasis should be placed on both conservative and surgical treatment
of paratendinopathy over the treatment of pathology of the tendon itself.
Introduction
The combination of tendon pain, swelling, and impaired performance should be

given the clinical label of tendinopathy, and should include the histopathological
entities peritendinitis and tendinosis38. The most common clinical diagnosis of
Achilles overuse injuries is paratendinopathy and / or tendinopathy (55-65%),
followed by insertional problems like retrocalcaneal bursitis and insertional
tendinopathy (20-25%) 12, 15, 16, 27. Differentiation between tendinopathy of the
main body of the Achilles tendon and paratendinopathy may be confusing54,
and frequently these entities coexist in the chronic phase. There is no consensus
17
on which causes the pain, the peritendineum, the tendon itself, or a combination
of both. Degeneration of the body of the Achilles tendon has been found during
autopsies in 34% of tendons in patients without complaints20. This finding
was confirmed in a study by Khan and co-workers, who identified abnormal
tendon morphology in 37 of the 57 symptomatic tendons (65%) and abnormal
morphology in 9 of 28 asymptomatic tendons (32%) using ultrasound23.
Another study concluded that there was no relationship between symptoms
and ultrasonographic intratendinous abnormalities in elite gymnasts8. These
studies imply that an area of intratendon abnormality of the Achilles tendon
itself is not necessarily the cause of pain. Since neovascularisation and enhanced
neurovascular growth into the peritendineum and myofibroblasts responsible
for the formation of permanent scarring, and the shrinkage of peritendinous
tissue have been shown in patients with chronic complaints of pain and stiffness
of their Achilles tendon, we postulate that the peritendineum is the main cause
of complaints14, 29, 31, 46.
In this chapter, we discuss the basic science of Achilles paratendinopathy, its
diagnosis and treatment.
Anatomy
The anatomy of the Achilles tendon is different from that of other tendons inserting
into the foot. It lacks a true synovial sheath but rather has a peritendineum. The
peritendineum functions as an elastic sleeve and permits free movement of the
tendon within the surrounding tissues. The peritendineum forms a thin space
between the tendon and crural fascia. Under the paratenon, the entire Achilles
tendon is surrounded by a fine, smooth connective tissue sheath called the
epitenon. On its outer surface, the epitenon is in contact with the paratenon. The
inner surface of the epitenon is continuous with the endotenon, which binds the
collagen fibers and fiber bundles together46.
The peritendineum is richly vascularized, and provides blood supply to the
Achilles tendon itself5, 18, 28, 46. The neural supply to the Achilles tendon and the
surrounding peritendineum is provided by nerves from the attaching muscles
and by small fasciculi from cutaneous nerves, in particular the sural nerve61.
The number of nerves and nerve endings is relatively low, and many nerve
fibers terminate in the peritendineum or on the tendon surface18. These nerves
follow the vascular channels within the long axis of the tendon, anastomose via
obliquely and transversely oriented fibers, and finally terminate in sensory nerve
endings18. Achilles paratendinopathy involves inflammation of the peritendinous
tissues54. In patients with Achilles tendon overuse injury, the sensory nerve
endings accompany the peritendinous neovascularization2.
Pathophysiology
Based on a histopathologic examination, findings in Achilles tendinopathy can

be divided into peritendinous changes and intratendinous abnormalities; but
16
Paratendinopathy
frequently these entities coexist16.

In the acute phase of Achilles tendinopathy, caused by acute overexertion,
blunt trauma, or acute muscle fatigue, inflammatory cell reaction, circulatory
impairment, and edema formation occur18, 46. Crepitus, due to movement of
the Achilles tendon within a peritendineum filled with fibrin exudate, may be
present. If the treatment of this acute condition fails, or if the acute condition
has been overlooked, the fibrin may organize and form adhesions to the tendon,
peritendineum and crural fascia causing a chronic condition46.
Two types of cells have been identified in the peritendinous tissue in the
chronic phase of Achilles tendinopathy: fibroblasts and myofibroblasts29. During
biological processes that include extensive tissue remodeling, fibroblasts may
acquire morphological and biochemical features of contractile cells which have
been named myofibroblasts7. The myofibroblasts have stress fibers composed of
α–smooth muscle actin in their cytoplasm and thus are capable of creating forces
required for wound contraction7. In chronic Achilles tendinopathy, these cells
are especially well established at the sites of scar formation, and it is estimated
that about 20% of peritendinous cells are myofibroblasts29. The myofibroblasts
synthesize abundant amounts of collagen and are believed to be responsible for
the formation of permanent scarring and the shrinkage of peritendinous tissue
around the tendon14, 29. These cells most probably also play an important role in
the clinical symptoms. They can induce and maintain a prolonged contracted
state in the peritendinous adhesions around the tendon and thus influence the
development of a contracture14, 29. This, in turn may lead to constriction of vascular
channels and to impaired circulation and further contribute to the pathogenesis
of Achilles tendinopathy. The proliferating connective tissue around the Achilles
tendon causes increased intratendinous tension and pressure resulting in
increased friction between the tendon, peritendineum, crural fascia, and the
skin14.
History & Physical Examination
Pain and swelling around the Achilles tendon often increase with activity in
patients with paratendinopathy54. In contrast, the symptoms of tendinopathy
tend to decrease with activity and fibrosis and tenderness are more localised54.
The history of Achilles tendinopathy, although often typical, is not of itself
diagnostic. Physical examination with inspection and tenderness on palpation
are important diagnostic criteria37.
Pain is the cardinal symptom of Achilles paratendinopathy that leads a patient
to seek medical help, and it is the most common measure used to classify the
severity of the disorder18. In patients with acute Achilles paratendinopathy the
tendon is diffusely swollen and on palpation tenderness is usually greatest
in the middle third of the tendon. The pain is often most prominent on the
medial side59. On physical examination, a paratendinopathy manifests itself as
peritendinous crepitus as the tendon tries to glide within the inflamed covering.
Diffuse swelling may be noted54 (figure1).
17
Figure 1: A 45- year old male with diffuse swelling over the left Achilles tendon,
based on a paratendinopathy.
Typically, in patients with acute symptoms, the area of swelling and tenderness
does not move when the ankle joint is dorsiflexed. Areas of increased erythema,
local heat, and palpable tendon nodules or defects may also be present at
clinical examination. In addition, ankle instabilities and malalignment of the
lower extremity, especially in the foot, should be sought in patients with Achilles
complaints18, 36, 46.
In chronic Achilles paratendinopathy, exercise-induced pain is still the cardinal
symptom while crepitation and swelling diminish18, 36, 46. A tender, nodular
swelling usually indicates tendinopathy of the main body of the tendon; these
focal tender nodules move as the ankle is dorsi- and plantarflexed9, 11.
Differential diagnoses of paratendinopathy are tendinopathy, partial rupture, an
insertional disorder, anomalous soleus muscle and complete rupture. All these
show a marked overlapping of the findings in history and physical examination.
In clinical practice overuse injuries often do have features of more than one
pathophysiological entity. However, in most cases thorough history and physical
examination should point towards the correct diagnosis44.
Radiological Diagnosis
In the acute phase of Achilles tendinopathy, ultrasonography reveals fluid

surrounding the tendon43. In its more chronic form, peritendinous adhesions can
be seen as thickening of the hypo-echoic peritendineum with poorly defined
borders18, 19, 30. Discontinuity of tendon fibers, focal hypo-echoic intratendinous
areas, localized tendon swelling and thickening are the most characteristic
ultrasonographic findings in patients with surgically verified intratendinous
lesions of the Achilles tendon18, 43, 50. Ultrasound (US) imaging is a cost-effective
and accurate investigation to evaluate disorders of the Achilles tendon40.
MRI has been used extensively to visualize tendon pathology as it satisfies two
16
Paratendinopathy
fundamental principles of imaging. It provides high intrinsic tissue contrast,

which is able to separate normal from abnormal tendons, and gives high spatial
resolution that can identify detailed anatomic structures51, 53. The ability of MRI
to acquire images from multiple planes (axial, sagittal, coronal) is also a clear
advance22, and is especially important for pre-operative planning. In acute
Achilles paratendinopathy, MRI shows high signal around the Achilles tendon
on Short Tau Inversion Recovery (STIR) and T2 (hyper- intense signal in water
rich regions) weighted images (fig. 2). In the chronic phase the peritendineum
is thickened on MRI. The disadvantages of MRI are its relatively high cost, limited
availability in some countries, time-consuming scanning, and slow and often
incomplete resolution of signal changes after operative intervention18, 18, 46, 53.
Figure 2: T2- weighted axial image of a right leg, showing high signal intensity
around the Achilles tendon, based on an acute paratendinopathy.
Treatment
The main goal of the management of an acute Achilles tendon overuse injury
is to alleviate the pain and to prevent the complaint from becoming more
chronic. In patients who present with long-standing pain, alleviation of pain
still predominates the management strategies adopted, and little attention is
paid to address predisposing factors and etiological causes of the complaint.
Management has never been focused on prevention of a tendon rupture.
There is no evidence that patients with complaints of Achilles tendinopathy /
paratendinopathy are more prone to tendon rupture.
Little reliable experimental or clinical scientific work has been performed on the
pathophysiology, etiology, natural course, and management of Achilles tendon
overuse injuries36, 46. Without scientific backing and a firm understanding of the
nature of tendon injuries and other tendon disorders, it is difficult to prescribe
an appropriate management regimen for Achilles tendon problems. Both
conservative and surgical regimens vary considerably among countries, clinics,
and physicians. Most management regimens are based only on what empirically
seemed to work without much scientific support18, 36, 46.
In the early phases of Achilles tendinopathy and / or paratendinopathy, various
forms of conservative treatment are normally used1, 6, 10, 18, 21, 32, 36, 48, 49, 55, 66. Operative
17
treatment is recommended for patients who do not respond adequately to a 3 to

6 month trial of appropriate conservative treatment 26, 27, 34, 35, 42, 47, 56, 57, 66.
Natural course
Little is known about the natural course of Achilles tendinopathy and / or
paratendinopathy. An 8-year follow-up study showed that on the long-term the
condition of these patients was self-limiting. Seventy of the 83 patients (83%)
were able to return to full levels of physical activity and at 8 years 78 patients
(94%) were asymptomatic or had only mild pain on strenuous exercise48. Delay of
up to six months between the onset of symptoms and initiation of conservative
management did not compromise long-term outcome. Nevertheless, 24 of the
83 patients (29%) failed to respond to conservative management and underwent
operative management. Also, even at the 8-year follow-up, there was a difference
between the involved and the uninvolved sides in the performance tests, clinical
examination and US findings. Furthermore, almost half of the patients (41%)
developed some overuse symptoms (pain with or without swelling and stiffness)
also in the initially uninvolved Achilles tendon 44, 48.
Conservative treatment
In early Achilles tendinopathy and / or paratendinopathy, various forms of
conservative management are used46, 53. Initial non-operative management
aims to identify and correct predisposing factors of the chronic Achilles
tendon problems53. Orthoses are used to correct malalignments, while the
training program is modified to place less strain on the Achilles tendon, and
if the symptoms are severe, the lower extremity is rested for a short time44, 46,
63
. Cryotherapy is often applied, producing an analgesic effect, reducing the
metabolic rate of tendons and decreasing the extravasation of blood and proteins
from neovessels by vasoconstriction4, 24, 25. Although the use of nonsteroidal anti-
inflammatory drugs (NSAIDs) did not positively affect the outcome of Achilles
tendinopathy in a randomized clinical trial3, they are often used for management
of pain and inflammation from Achilles paratendinopathy in the acute phase53.
The use of corticosteroid injections around the Achilles tendon should not be
liberal, and should only be administered by experienced physicians45, 53. Cast
immobilization and friction therapy are often applied but lack scientific evidence.
A positive effect of brisement of adhesions secondary to paratendinopathy has
been described, wherein sterile saline, with or without an anesthetic, is injected
into the potential space between the peritendineum and Achilles tendon,
thereby releasing adhesions17. Unfortunately these injections will most likely be
insufficient to reverse the constrictions in chronic paratendinopathy58 (figure3).
16
Paratendinopathy
Figure 3: Example of adhesions in Achilles paratendinopathy.
Surgical treatment
Surgical management is recommended to those patients who do not
adequately respond to 3 to 6 months of conservative management13, 26, 27, 33, 34, 42,
55-57, 66
. However, no prospective randomized studies comparing operative and
conservative management of Achilles tendinopathy and/ or -paratendinopathy
have been published, and most of our knowledge on management efficacy is
based on clinical experience and descriptive studies36, 46.
Tallon and co-workers reviewed studies that reported surgical outcomes in
the management of chronic Achilles tendinopathy and/or paratendinopathy62.
Methodology scores of the studies were generally low, indicating the limitations
of these studies. A negative correlation was found between reported success
rates and overall methodology scores, but the positive correlation between
year of publication and overall methodology score suggests that the quality of
studies is improving62.
Surgical techniques for Achilles paratendinopathy or a combination of
paratendinopathy with intratendinous lesions are tenolysis and excision of
adhesions of the peritendineum and Achilles tendoscopy13, 26, 33, 34, 39, 41, 42, 56, 60, 64, 65.
In Achilles paratendinopathy, many authors recommend that after longitudinal
division of the crural fascia, the peritendineum is incised and any macroscopic
adhesions are excised13, 26, 33, 34, 42, 56. In some studies the adhesions were found
mainly between the Achilles tendon and peritendineum42, 56, while others have
reported that the peritendineum was adhered mainly to the crural fascia, or even
to the skin26, 52.
A few studies describe endoscopy-assisted surgical release of adhesions around
the Achilles tendon 39, 41, 60, 64, 65. Preliminary results have been good, and the
endoscopic technique may have the advantage of reducing postoperative
morbidity39, 41, 60, 64. One of the authors (CvD) has been performing Achilles
tendoscopy for isolated paratendinopathy and combined chronic Achilles
tendinopathy and paratendinopathy over the last decade. It involved a release
of the peritendineum, hereby ‘denervating’ it, leaving the tendon proper
untouched. This technique provides good short- and midterm results, as
described in a retrospective study by Steenstra and co-workers60. A prospective
series is currently under investigation. With this procedure the intratendinous
changes cannot be addressed, so, when on physical examination the tendon
17
itself seems to cause the majority of complaints, Achilles tendoscopy is indicated.

This emphasizes the importance of well-aimed diagnosis when considering
endoscopic treatment.
Unfortunately, there are no studies comparing different surgical techniques in

treatment of Achilles paratendinopathy.
In most studies, surgery for Achilles tendon overuse injury has given satisfactory
results in 75 to 100% of patients. Most of these reports have been retrospective,
and only in a few the results have been based on objective evaluations. In addition,
the underlying pathology has usually been heterogeneous 13, 26, 33, 34, 42, 55-57, 66. In
a report by Paavola and co-workers, open operative management of Achilles
paratendinopathy with or without tendinopathy of the main body of the Achilles
tendon resulted in good and acceptable short-term results, using subjective,
clinical and functional tests as outcome criteria47. Isolated paratendinopathy was
treated by longitudinal division of the crural fascia and adhesions between the
peritendineum and the crural fascia were excised. In combined tendinopathy
and paratendinopathy, additional longitudinal incision of the tendon itself was
performed and the intratendinous lesion was removed. A lower complication
rate of operative management and a trend to better recovery was observed in
patients with pure paratendinous adhesions than in those with paratendinous
adhesions combined with an intratendinous lesion47.
An 11% overall complication rate was documented in a series of 432 consecutive
patients39. In that study, most of the complications (54%) involved compromised
wound healing and this problem seemed to appear more frequently in patients
operated on for a partial Achilles tendon rupture than for Achilles tendinopathy
only49.
Conclusion
The etiology, pathogenesis and natural course of Achilles tendinopathy are

largely unknown. Most often pathology exists from a combined involvement
of the tendon proper and the peritendineum. It is questionable which of these
structures is the cause of pain; since several studies have been published on
asymptomatic degenerative changes inside the tendon, the tendon proper itself
might not cause complaints. Neovascularisation and enhanced neurovascular
growth into the peritendineum, and myofibroblasts responsible for the
formation of permanent scarring and the shrinkage of peritendinous tissue
have been shown in patients with chronic complaints of their Achilles tendon.
More emphasis should be placed on both conservative and surgical treatment of
paratendinopathy, above the treatment of pathology of the tendon itself. Basic
research on the origin of the pathology will guide to a better understanding of
complaints, leading to the most effective treatment options.
Acknowledgement
The financial support of the Stichting Amphoraest (Foundation) is acknowledged
16
Paratendinopathy
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17
Achilles Tendon Structure and Healing
“Seeking clarity in the presence of disorganization”
(Pankaj Sharma)
Chapter 8.
Achilles Tendon
Structure and Healing
Pankaj Sharma, Nicola Maffulli
Take Home Message
• Tendinopathy occurs secondary to a disorganized haphazard healing response.

• Tendon healing occurs in three overlapping phases.
• Despite healing injured tendon never regains the mechanical properties of
normal tendon.
Introduction
Over the past few decades, disorders of the Achilles tendon have increased
secondary to greater participation in recreational and competitive sports. Despite
this, our understanding of the underlying pathophysiology remains limited.
Consequently, the management of Achilles tendon injury poses a considerable
challenge for clinicians. This chapter describes the structure of tendons and
reviews the pathophysiology of tendon injury and healing.
23
Tendon Structure
Tendons vary in form, they can be rounded cords, strap-like bands or flattened
ribbons. When healthy, they appear brilliant white and have a fibroelastic
texture. Tendon tissue is composed of tenoblasts and tenocytes lying within a
network of extracellular matrix (ECM). Tenoblasts are spindle shaped, immature
tendon cells. Their cytoplasm contains numerous organelles reflecting their high
metabolic activity33. With ageing, tenoblasts become elongated and develop
into tenocytes33. Together, tenoblasts and tenocytes account for 90-95% of the
cellular elements of tendons33. The remaining 5-10% of the cellular elements
of tendons consists of chondrocytes at the bone attachment and insertion
sites, synovial cells of the tendon sheath, and vascular cells, including capillary
endothelial cells and smooth muscle cells of arterioles60.
Tenocytes synthesize collagen, all components of the ECM, and are also active in
energy generation52. With increasing age, metabolic pathways shift from aerobic
to more anaerobic energy production32. Oxygen consumption by tendons and
ligaments is 7.5 times lower than skeletal muscles67. This low metabolic rate and
well developed anaerobic energy generation capacity, allows tendons to carry
loads and maintain tension for long periods, and avoids the risk of ischaemia
and subsequent necrosis. The drawback of this specific adaptation is that a low
metabolic rate results in slow healing after injury68.
Water accounts for approximately 70% of tendon mass, and collagen type I
accounts for 65-80% of dry mass52. Tenocytes and tenoblasts lie between the
collagen fibres along the long axis of the tendon68. Collagen is arranged in
hierarchical levels of increasing complexity, beginning with tropocollagen, a
triple-helix polypeptide chain, which unites into fibrils; fibers (primary bundles);
fascicles (secondary bundles); tertiary bundles; and the tendon itself (Figure 1)30.
TERTIARY BUNDLE
TENDON
SECONDARY BUNDLE
(FASCICLE)
EPITENON
COLLAGEN FIBRE
ENDOTENON
PRIMARY BUNDLE
(SUBFASCICLE)
TROPOCOLLAGEN
Figure 1: Schematic structure of a normal tendon.
24
The ground substance of the ECM surrounding the collagen and the tenocytes
is composed of proteoglycans, glycosaminoglycans (GAG), glycoproteins and
several other small molecules33. The strongly hydrophilic nature of proteoglycans
enables rapid diffusion of water soluble molecules and migration of cells.
Adhesive glycoproteins, such as fibronectin and thrombospondin, participate
in repair and regeneration processes in tendon31. Tenascin-C, another important
component of the tendon ECM, is abundant in the tendon body and at the
osteotendinous (OTJ) and myotendinous (MTJ) junctions34. Tenascin-C contains
a number of repeating fibronectin type III domains, and, following stress-
induced unfolding of these domains it also functions as an elastic protein34. The
expression of Tenascin-C is regulated by mechanical strain, and is up-regulated
in tendinopathy45. Tenascin-C may play a role in collagen fibre alignment and
orientation43.
The Achilles tendon is covered by paratenon, a loose areolar connective tissue
consisting of type I and III collagen fibrils, some elastic fibrils, and an inner
lining of synovial cells. Deep to the paratenon, the whole tendon is covered by
the epitenon, a fine, loose connective-tissue sheath containing the vascular,
lymphatic, and nerve supply to the tendon. The epitenon extends deep within
the tendon, between the tertiary bundles as the endotenon. The endotenon
invests each tendon fibre35.
At the MTJ, tendinous collagen fibrils are inserted into deep recesses formed by
myocyte processes, allowing the tension generated by intracellular contractile
proteins of muscle fibres to be transmitted to the collagen fibrils40. This complex
architecture reduces the tensile stress exerted on the tendon during muscle
contraction40. However, the MTJ still remains the weakest point of the muscle-
tendon unit40. The OTJ is composed of four zones: a dense tendon zone,
fibrocartilage, mineralized fibrocartilage, and bone11. The specialized structure of
the OTJ prevents collagen fibre bending, fraying, shearing and failure21.
Blood Supply
Tendons receive their blood supply from: the intrinsic systems at the MTJ and
OTJ, and from the extrinsic system via the paratenon or the synovial sheath17. At
the MTJ, perimyseal vessels from the muscle continue between the fascicles of
the tendon17. However, these vessels are unlikely to extend beyond the proximal
third of the tendon17. The blood supply from the OTJ is sparse, and limited to
the insertion zone of the tendon, although vessels from the extrinsic system
communicate with periosteal vessels at the OTJ17.
In the Achilles tendon, the paratenon provides the extrinsic component of the
vasculature. Tendon vascularity is compromised at junctional zones and sites of
torsion, friction or compression. In the Achilles tendon, angiographic injection
techniques have demonstrated a zone of hypovascularity 2-7 cm proximal to the
tendon insertion and laser Doppler flowmetry has demonstrated substantially
reduced blood flow near the Achilles tendon insertion9,17. In general, tendon
blood flow declines with increasing age and mechanical loading9.
25
Biomechanics
The tensile strength of tendons is related to thickness and collagen content,

and a tendon with an area of 1 cm2 is capable of bearing 500-1000 kg58. In the
human Achilles tendon, forces of 9 kN, corresponding to 12.5 times body weight,
have been recorded during running. Since these forces exceed the single-load
ultimate tensile strength of the tendon, the rate of loading may also play an
important role in tendon rupture16. Tendons are at the highest risk for rupture
if tension is applied quickly and obliquely, and highest forces are seen during
eccentric muscle contraction.
Tendon response to mechanical loading can be displayed on a stress-strain curve
(Figure 2).
80
60
STRESS
40
20
2 4 6 8
MACROSCOPIC FAILURE
STRAIN (%)
LINEAR DEFORMATION MICROSCOPIC FAILURE
Figure 2: Stress-strain curve demonstrating the basic physical properties of normal

tendons.
Collagen fibres and fibrils display a crimped configuration at rest20. The initial
concave portion of the curve (toe region), where the tendon is strained up to
2%, represents extension of the collagen fibres and the crimp pattern is lost16.
Beyond 2% strain, the tendon deforms in a linear fashion due to intramolecular
sliding of collagen triple helices, and the fibres become more parallel47. Providing
the strain remains below 4%, the tendon behaves in an elastic fashion, returning
to its original length upon unloading19. Microscopic failure occurs when the
strain exceeds 4%, and, beyond 8-10% strain, macroscopic failure occurs from
intrafibril damage by molecular slippage56.
26
Clinical presentation
The main symptom of Achilles tendinopathy is pain. In the initial stages

patients may remain asymptomatic, although histopathological testing would
demonstrate changes at this stage. Therefore, even in patients presenting acutely,
it is likely that the histopathological process of tendinopathy has been present
for quite some time. In the initial stages, pain usually occurs at the beginning
and end of exercise sessions. As the pathologic process progresses, pain may
occur during exercise, and, in severe cases, it may interfere with activities of daily
living. In the acute phase, the tendon is diffusely swollen and edematous, with
maximal tenderness being present 2 to 6 cm proximal to the tendon insertion.
A fibrin-rich fluid can often be present around the tendon, resulting in palpable
crepitation. As the condition becomes chronic, exercise-induced pain remains
as the predominant symptom, however, crepitation and effusion diminish. A
tender, fusiform or nodular swelling is often present in chronic cases.
Aetiology and Pathophysiology
Tendon injuries can be acute or chronic, they are caused by intrinsic or extrinsic
factors, either alone or in combination. In acute trauma, extrinsic factors
predominate, whilst in chronic cases intrinsic factors also play a role. In Achilles
tendinopathy, it is likely that an interaction between intrinsic and extrinsic
factors occurs. Intrinsic factors such as alignment and biomechanical faults are
claimed to play a causative role in two-thirds of athletes with Achilles tendon
disorders39. In particular, hyperpronation of the foot has been linked with an
increased incidence of Achilles tendinopathy50.
The main pathological stimulus for degeneration is believed to be excessive
loading during vigorous physical activity57. It seems intuitive that in the
presence of intrinsic risk factors, excessive loading is likely to carry a greater risk
of inducing tendinopathy. Repetitive loading beyond physiological threshold
results in either inflammation of the tendon sheath, degeneration of the tendon,
or a combination of both10. It is possible that different stresses induce different
responses. Active repair of fatigue damage must occur, or tendons would
weaken and eventually rupture36. Resident tenocytes probably regulate such
repair processes, by modulating a fine balance between ECM production and
degradation. Tendon damage may even occur from stresses within physiological
limits, as frequent cumulative microtrauma may not allow adequate time for
repair8. Microtrauma can also result from non-uniform stress within tendons,
producing abnormal load concentrations and frictional forces between the
fibrils, resulting in localised fibre damage8.
Histologically, tendinopathy is characterized by a disordered haphazard healing
response. Inflammatory cells are absent, and intratendinous collagen degeneration
occurs. In addition, fibre disorientation and thinning, hypercellularity, scattered
vascular ingrowth, and increased interfibrillar glycosaminoglycans are seen30.
Electron microscopy has demonstrated various types of tendon degeneration
that occur either alone or in combination, namely: hypoxic degeneration, hyaline
27
degeneration, myxoid degeneration, fibrinoid degeneration, lipoid degeneration,

calcification, and fibrocartilaginous and bony metaplasia. However, myxoid and
lipoid degeneration are most commonly encountered in the Achilles tendon.
Macroscopically, these degenerative processes result in glistening white tendon
tissue being replaced by amorphous grey-brown tissue.
The underlying pathophysiological process that results in tendinopathy also
remains undetermined. It is possible that there may be several pathways that can
result in tendon degeneration. The following mechanisms have all been proposed
as initiators of tendinopathy: Hypoxia, ischaemic damage, oxidative stress,
hyperthermia, impaired apoptosis, inflammatory mediators, fluoroquinolones,
and matrix metalloproteinase imbalance12,13,18,26,55,62,64,69.
Pain in tendinopathy
The exact cause of pain in tendinopathy remains unclear. Classically, pain was
believed to arise secondary to inflammation. However, chronically painful
Achilles tendons do not demonstrate inflammation. In addition, many tendons
with intratendinous pathology detected on MRI or ultrasound are not painful37.
Pain may originate from a combination of mechanical and biochemical causes37.
Recently attention has focused on chemical irritants and neurotransmitters as
potential mediators of pain in tendinopathy. Lactate, glutamate, prostaglandin PG
E2 and Substance P have all been implicated as potential pain mediators2,5,27,42,71.
Furthermore, an opioid system has been demonstrated in the Achilles tendon of
rats3. Under normal conditions, a balance probably exists between nociceptive
and anti-nociceptive peptides14. However, this balance may be altered in
pathological conditions14.
Tendon Healing Following Acute Injuries
Tendon healing studies have predominantly been performed on transected

animal tendons or ruptured human tendons, and their relevance to human
tendinopathy with its associated healing failure response remains unclear59.
Tendon healing occurs in three overlapping phases. The initial inflammatory
phase is characterized by erythrocytes and inflammatory cells infiltration at
the site of injury. The predominant inflammatory cell seen is the neutrophil;
although in the first 24 hours monocytes, macrophages and phagocytose
necrotic materials predominate. Vasoactive and chemotactic factors are released
at the injury site. This results in increased vascular permeability, initiation of
angiogenesis, stimulation of tenocyte proliferation, and recruitment of more
inflammatory cells48. Tenocytes gradually migrate to the wound, and type III
collagen synthesis is initiated51.
The regenerative phase commences after a few days and lasts for a few weeks.
A peak in collagen type III synthesis is seen during this stage. In addition, water
content and glycosaminoglycan concentrations also remain high during this
stage51.
28
After approximately 6 weeks, the remodeling stage commences. A decrease

in cellularity, collagen and glycosaminoglycan synthesis occurs, resulting in
resizing and reshaping of the healing tissue. The remodeling phase can be
divided into a consolidation and maturation stage65. The consolidation stage
runs approximately from week 6 to week 10. Tenocyte metabolism remains high
during this period, and repair tissue changes from cellular to fibrous. Synthesis
of type I collagen predominates, and tenocytes and collagen fibres become
aligned in the direction of stress1,28. After 10 weeks, the maturation stage occurs
and continues for up to a year. During this stage, the healing fibrous tissue is
gradually converted to scar-like tendon tissue28. During the latter half of this
stage tenocyte metabolism and tendon vascularity decline6.
Two different pathways of tendon healing have been described. Intrinsic
healing is achieved via proliferation of epitenon and endotenon tenocytes;
whilst, extrinsic healing, relies on invasion of cells from the surrounding tendon
sheath and synovium25. It is believed that epitenon tenoblasts initiate the repair
process by proliferation and migration44. Epitenon tenoblasts alone are capable
of healing severed tendons, without relying on adhesions for vascularity or
cellular support24. However, internal tenocytes also contribute to the intrinsic
repair process and secrete larger, more mature collagen than epitenon cells23.
Different cell populations produce different collagen types at different time
points. Epitenon cells are initially responsible for collagen production, whilst at a
later stage this role is taken over by endotenon cells29. It is difficult to quantify the
exact contribution of each cell type; and the relative contribution of each cell type
is likely to be influenced by the type of trauma sustained, anatomical position,
presence of a synovial sheath, and the amount of stress induced by motion after
repair has taken place38. Intrinsic healing results in improved biomechanics and
fewer complications. In particular, a normal gliding mechanism within the tendon
sheath is preserved. In extrinsic healing, scar tissue results in adhesion formation
which disrupts tendon gliding63. Different healing patterns may predominate in
particular locations, for example, extrinsic healing tends to prevail in torn rotator
cuffs66.
Modulation of Healing
As previously stated tendinopathy results from a suboptimal healing response,

which in turn is caused by an imbalance between matrix degeneration
and synthesis. The most important regulators of the ECM are the matrix
metalloproteinases (MMPs). MMPs are a group of zinc and calcium dependent
endopeptidases which are responsible for the degradation of collagen in
tendons. Tendon matrix constantly remodels, with higher rates of turnover at
sites exposed to high levels of strain. This mechanism is responsible for the repair
of microtrauma that results from repetitive loading. In Achilles tendinopathy, the
expression of MMP3 mRNA is downregulated4. Decreased MMP3 expression may
therefore lead to tendinopathic changes in tendons. Hence, increased MMP3
expression may be necessary for appropriate tissue remodeling and prevention
of tendinopathic changes.
29
The healing response also results in release of growth factors and cytokines from
platelets, polymorphonuclear leukocytes, macrophages and other inflammatory
cells. These growth factors induce neovascularization and chemotaxis of
fibroblasts and tenocytes which stimulate fibroblast and tenocytes proliferation
and synthesis of collagen46.
Nitric oxide is a short lived free radical, which may play a role in several aspects
of tendon healing. Many actions have been attributed to nitric oxide: it is
bactericidal, can induce apoptosis in inflammatory cells, and causes angiogenesis
and vasodilatation22,70. Nitric oxide synthase is responsible for synthesizing nitric
oxide from L-arginine. Experimental studies have shown that levels of nitric oxide
synthase peak after seven days and return to baseline 14 days after tenotomy
of rat Achilles tendons49. Inhibition of nitric oxide synthase reduced healing
and resulted in decreased cross sectional area and a reduced failure load49.
Commercially available glyceryl trinitrate (GTN) patches have been used as a
vehicle to deliver nitric oxide to the site of tendinopathy. Murrell and co-workers
conducted a double blind randomized controlled trial for the management
of Achilles tendinopathy. They found that 78% of patients receiving GTN and
rehabilitation were asymptomatic for activities of daily living at 6 months
compared to only 49% of patients receiving rehabilitation alone53.
Substance P is present in normal tendon tissue in small amounts, however, its
expression is increased in tendinopathy7. Experimental studies on ruptured
rat Achilles tendons have demonstrated that injection of Substance P around
sutured tendons enhanced stress at maximal load and work to maximal load61.
Hence, it is possible that Substance P plays a role in healing in tendinopathy.
Limitations of healing in acute tendon injuries
Despite remodeling, the biochemical and mechanical properties of healed

tendon tissue never match those of intact tendons. In spontaneously healed
transected sheep Achilles tendons, rupture force was only 56.7% of normal at
12 months15. One possible reason for this may be the absence of mechanical
loading during the period of immobilization.
Conclusion
Tendon injuries give rise to substantial morbidity, and current understanding of

the mechanisms involved in tendon injury and repair is limited. Further research
is required to improve our knowledge of tendon healing. This will enable specific
treatment strategies to be developed.
30
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31
16
Non-Operative Treatment
“The fool doth think he is wise, but the

wise man knows himself to be a fool. ”
(As You Like It, William Shakespeare)
Chapter 9.
Christopher Pearce, Brian Donley, James Calder
Take Home Message
• The treatment of non-insertional Achilles tendinopathy should begin with

conservative measures.
• Eccentric strengthening has become the first-line treatment of choice for non-
insertional Achilles tendinopathy with the greatest amount of evidence for its
effectiveness.
• The choice of second-line non-operative intervention depends somewhat on the
available resources but ESWT has shown results that are almost comparable to
an eccentric strengthening programme.
• More studies are required to robustly analyse the clinical results and
mechanisms of action of some of the newer conservative measures discussed in
this chapter.
Introduction
The mainstay of management in non-insertional Achilles tendinopathy is

conservative and surgery should only be considered once conservative measures
have failed. The first step may be to remove the precipitating factors by resting
or modifying training regimes. Foot and ankle malalignments may be addressed
17
by orthotics, and decreased flexibility, and muscle weakness may be treated by

appropriate physiotherapists. Active non-operative treatments may, however,
yield more rapid and longer lasting results as well as being more acceptable to
the athlete or patient than simply resting. Many different conservative modalities
may improve symptoms, signs and imaging appearance of the condition. As
there are still many unanswered questions regarding the aetiology of Achilles
tendinopathy, there are equally as many uncertainties regarding the mechanism
of action of some of these, purportedly successful, non-operative interventions.
This chapter reviews the clinical evidence for the various non-operative
treatments and attempts to elucidate some of the basic science behind them.
Drugs
Non-steroidal anti-inflammatory drugs have long been used as a first line

treatment in various musculo-skeletal complaints including tendinopathies1, 99.
Even topical applications of these drugs have been shown to be significantly
more effective than placebo in several studies29, 39, 61, 94. These were all very
short term studies however, with only clinical outcome measures. There is little
evidence to support or refute the use of topical or oral NSAIDs in the long term8.
The scientific basis behind the effectiveness of NSAIDs in the management of
tendinopathy must be questioned in the light of growing evidence for a lack of
inflammation in these conditions: virtually all histological studies have failed to
demonstrate inflammatory cells in the tendinopathic tissue3, 35, 49, 51, 52, 66, 86, 88. A
Cochrane review found weak evidence from three trials of a modest benefit of
NSAIDs for the alleviation of acute symptoms62. The short term benefit of these
drugs in tendinopathy is likely due to their analgesic rather than their anti-
inflammatory actions83. In a randomized study, Anstrom and Westlin10 found no
beneficial effects of NSAIDs in patients with Achilles tendinopathy compared
with placebo at any point up to 28 days of treatment. It is possible that these
drugs may even hinder recovery; Celecoxib has been shown to inhibit the tendon
cell migration and proliferation that is required for tendon healing106. There is
experimental evidence to suggest that NSAIDs may increase levels of leukotriene
B, and therefore may contribute to the development or progression of Achilles
tendinopathy55.
The role of corticosteroid injections in Achilles tendinopathy is also controversial.
Injections of corticosteroids have been shown to relieve the symptoms, swelling35
and even ultrasound appearance105 of tendinopathies. There may, however, be
other explanations for their efficacy, including their vasoconstrictive action by
reducing prostacyclin production, increasing adrenoceptor numbers, and their
inhibition of nitric oxide synthase103. The great concern with this treatment is the
increased risk of complete or partial rupture of the tendon after intra-tendinous
injection. There have been several case reports of tendon rupture following
corticosteroid injection12, 20, 23, 34, 40, 50, 53, 100, and the findings from animal studies of
decreased tendon strength associated with intra-tendinous injections provide
a basic science explanation for this11, 42, 44, 63. The risk/benefit analysis of steroid
injection in tendinopathy does not seem to favour its utility97.
16
Eccentric exercises
Eccentric exercises have the most evidence of effectiveness in the treatment of

non-insertional Achilles tendinopathy. This was confirmed in a recent systematic
review of the literature regarding non-operative treatment of midportion Achilles
tendinopathy59.
This method of treatment started with Stanish and colleagues in the 1980s101.
They reported a prospective study of 200 patients with a 6 week, once a day
eccentric loading regimen. 44% of their patients reported complete relief of pain
with a further 43% reporting a marked improvement. This study did not include
a control group however and the technique was not widely adopted until a
decade later.
Alfredson in 19987 reported excellent results in a non-randomised, prospective
trial. They compared a cohort of patients, in their 5th decade, who underwent
an eccentric strengthening regime with a similar aged cohort who had failed
traditional conservative methods and undergone surgery. All 15 patients in the
eccentric strengthening group significantly improved in terms of calf muscle
strength, to the point where there was no significant difference between the
injured and uninjured sides. They also had significantly improved pain scores
at 12 weeks and were back to normal activities. The eccentric strengthening
programme described in this paper is the one that has been most widely
adopted and consists of eccentric exercises performed twice daily, 7 days a week,
for 12 weeks. The calf is eccentrically loaded both with the knee straight and bent
with the patient’s toes on a step and the heel then lowered below the forefoot.
Each exercise is done in three sets of 15 repetitions. No concentric exercises are
performed, as the uninjured leg is used to get back up to the start position. The
patients start the programme using their body weight but add more weight by
wearing a heavy back pack as they start to tolerate the exercises better.
In 2001, a prospective randomised study by the same senior author found that
an eccentric exercise programme was significantly better than a concentric
programme with 82% in the eccentric group getting back to normal activities
after 12 weeks compared to only 36% in the concentric group58.
Other Scandinavian authors have reported similarly good results in prospective
randomised controlled trials93, 98. Outside of Scandinavia, investigators have also
found eccentric strengthening to be an effective non-operative intervention in
the treatment of non-insertional Achilles tendinopathy but the proportion of
good and excellent results is definitely lower57, 91, 95.
Despite the good clinical evidence for eccentric strengthening, only a few
studies have tried to explain the basic science behind its effectiveness. Stanish101
hypothesised that microscopic or macroscopic disruption of the tendon by
eccentric strengthening occurs and collagen growth is stimulated by means
of physiologic feedback loading. Ohberg showed that eccentric training led to
a significant reduction in tendon thickness and restoration of normal tendon
architecture on ultrasound at a mean of 3 and a half years follow up72. He also
demonstrated the close correlation between good clinical results with eccentric
training and a marked reduction in neovascularization of the tendon69. This was
confirmed in a later study, and no complications or adverse effects on tendon
17
microcirculation were found after a 12 week programme54.

Alfredson found that there was no effect on intra-tendinous glutamate levels
after a clinically successful eccentric strengthening programme in a prospective
study4.
Rees et al demonstrated that the peak tendon forces generated by eccentric
loading and concentric exercises do not differ significantly. They did note,
however, that during the eccentric exercises there was a pattern of sinusoidal
loading and unloading of the tendon that was not present during concentric
training. This difference in the mechanical loading profile between the different
muscle actions could provide an important stimulus for tendon remodelling, akin
to that seen in bone84. Moreover, the tendon was found to be more stretched
throughout the cycle in an eccentric compared to concentric programme. The
drawback of this study was that it used healthy volunteers although the authors
postulate that the force fluctuations may be even greater in tendinopathic
subjects. The ideal speed of the eccentric movement has yet to be established84.
Attempts have been made to improve the proportion of good and excellent
results with an eccentric strengthening programme by adding other treatments.
A prospective study by De Vos et al. showed that night splinting in addition to
eccentric exercises did not lead to any significantly better patient satisfaction
or Victorian Institute of Sport Assessment–Achilles (VISA-A) scores. Both groups
improved significantly, and the benefits remained at one year in the follow up
study. Night splinting does not add any benefit to an eccentric strengthening
programme. There was however no power analysis in this series, so it is possible
that the study did not have a sufficient sample size to detect such a benefit27, 28.
Rompe et al.89 recently showed in a prospective randomised controlled study
that eccentric strengthening plus repetitive low-energy shockwave therapy
was better than eccentric strengthening alone in terms of the VISA-A scores and
pain ratings at four months. The proportion of patients who were ‘completely
recovered’ or ‘significantly improved’ on the Likert scale was also significantly
better in the combined therapy group (82%) compared with the strengthening
alone group (56%).
Eccentric strengthening has become the treatment of choice for non-insertional

Achilles tendinopathy with the greatest amount of evidence for its effectiveness.
It requires a motivated patient but no special or expensive equipment, and has
been hailed as ‘probably the greatest single advance in the management of this
condition in the past 20 years’83. More research is ongoing into the mechanism of
action and the optimum speed, force and duration of the eccentric strengthening
programme.
Shock wave treatment
Extracorporeal shock wave therapy (ESWT) was originally developed for the
treatment of kidney stones, and has since been used to treat various soft tissue
conditions. It has shown particular benefit in the treatment of enthesopathies
16
and calcific tendinopathies37, 38, 92, 96. Presently, it is only approved by the
Food and Drug Administration in America for plantar fasciopathy and lateral
epicondylopathy. Shock wave therapy is traditionally categorised as either low
energy (<0.2 mJ/mm) or high energy (>0.2 mJ/mm). Low energy treatment is
generally well tolerated, with some discomfort, does not require anaesthesia,
and is usually given in multiple treatment sessions. High-energy therapy is more
painful and usually requires either local, regional or general anesthesia36.
The results of ESWT in non-insertional Achilles tendinopathy are conflicting. The

first prospective randomized controlled trial (PRCT) (Level II evidence) published
in the English language literature was against its benefit with no difference in
pain relief found between the shock wave therapy group and the control group26.
The protocols in this trial were different to those previously established, in that
the 49 patients were treated once a month for three months. Two older patients
in the treatment group also suffered tendon ruptures prompting the authors to
advise caution in using this treatment modality in older patients. The authors
acknowledged however, that the study was underpowered as they stated that
the confidence intervals include the potential for a clinically relevant treatment
effect.
A more recent PRCT evaluated ESWT against sham ESWT in a sufficiently powerful
study. All patients also underwent strengthening exercises and eccentric training
at the same time. The results in terms of the (unvalidated) American Orthopaedic
Foot and Ankle Society (AOFAS) hindfoot scale were significantly better in the
treatment group, especially amongst women. The Visual Analogue Scores (VAS)
for pain were better in both groups but there was no significant difference
between them82.
In a non-randomised case control study of high-energy ESWT in patients
with chronic non-insertional Achilles tendinopathy who had at least 3 forms
of traditional non-operative measures fail for a minimum of 6 months, Furia36
reported significantly better VAS and Roles and Maudsley scores in the treatment
group. These results were maintained at 12 months follow up with no significant
complications.
When compared with eccentric strengthening in a randomized controlled trial,

ESWT showed similarly favourable outcomes in Achilles tendinopathy with
around a 60% of the patients completely recovered or significantly improved in
both of the treatment groups. The results were significantly better than those in
the ‘wait and see’ control group91. The success rate of 60% was lower than that
seen in other studies using eccentric strengthening but this maybe because one
third of the patients in this study were not athletic and the results are known to
be worse in those individuals95.
Several theories exist as to the mechanism by which ESWT exerts its effect on
tissues and cells. There appear to be two aspects to the clinical response to shock
waves. The first is their effect on pain receptors and the other in promoting soft
tissue healing.
In the peripheral nervous system, ESWT leads to selective dysfunction of
17
sensory, unmyelinated nerve fibres either directly or through the liberation of

neuropetides. Changes in the dorsal root ganglion have also been reported
implicating both a central and peripheral nervous system role in mediating
shock wave-induced long-term analgesia90.
Shock waves generate high stresses that act at boundary interfaces and also
generate tensile forces that cause cavitation68. This is thought to cause interstitial
and extracellular disruption which then leads to healing of the tissue, through a
mechanism that is not fully understood, although work has been performed to
try to elucidate this.
Chen et al. showed enhanced tendon healing after shock wave treatment in
collagenease-induced Achilles tendinopathy in rats. They reported an increase in
TGF-β1 and IGF-I expression which, they postulate, may play a role in healing of
tendinopathic tissue21. Han et al have recently published evidence for a significant
decrease in some interleukins85 and matrix metalloprotienases (MMPs) after
shock wave treatment on cultured tenocytes41.
Shock wave therapy appears to have a role in the management of Achilles

tendinopathy, but questions remain as to what dosage and delivery regimen is
the most effective. We also have a long way to go in terms of ascertaining how
exactly it works. It will never be a first line treatment due to the success and
relative inexpensiveness of eccentric strengthening regimens, but it is a useful
additional option in recalcitrant cases prior to considering surgery.
Nitric oxide
Studies have evaluated the clinical response to topical glyceryl trinitrate

(GTN) for the treatment of chronic extensor tendinopathy78 and supraspinatus
tendinopathy76 with some improvement in symptoms. In 2004, Paoloni et
al77 in a randomized, double-blind, placebo-controlled trial suggested that
topical GTN may improve the outcome in the management of noninsertional
Achilles tendinopathy. They reported a significant improvement in pain at rest,
during activity and decreased tenderness over the tendon at 12 and 24 weeks
of treatment. Pain related to a single stance 10 hop test was also less in the
treatment group at 24 weeks. The authors suggested that GTN may modulate
local nitric oxide (NO) levels affecting fibroblast activity and collagen synthesis77.
Hunte and Lloyd-Smith point out one of the potential problems with this study in
that the intervention group required more paracetamol to treat headaches than
the control group, which raised dome doubts about the levels of blinding by the
end of the study period45. A follow up study (of 90% of the patients) 3 years after
cessation of treatment found that there were still significant differences between
the two groups with 67% of the control group symptom free compared with 88%
from the study group.
A subsequent randomised controlled trial in Achilles tendinopathy found that
GTN did not offer any additional clinical benefit over standard non-operative
treatment for non-insertional Achilles tendinopathy. After 6 months of
treatment, there was no significant difference in scores between the groups for
16
pain or disability scores. Histological examination did not show any difference
in neovascularization, collagen synthesis, or stimulated fibroblasts between the
2 groups48. This study had no power calculation, and therefore the sample size
of 40 patients may have been too small to detect any difference between the
groups.
Nitric oxide is a potent free radical that is produced by the nitric oxide synthase
(NOS) family of enzymes. It functions as an important biological signalling and
effector molecule in inflammation and immunity. Overproduction of nitric oxide,
however, can be toxic and contribute to tissue damage. Increased levels of nitric
oxide have been implicated in a number of degenerative conditions including
tendinopathy14, 18, 43, 67.
There is limited scientific basis on which to recommend GTN therapy for non-
insertional Achilles tendinopathy, and the mechanism of action of topical
glyceryl trinitrate on human tendon in vivo remains unknown.
Ultrasound and injection therapies
Therapeutic ultrasound is widely available and used around the world in a variety
of soft tissue conditions22, 87.
Therapeutic ultrasound may reduce the swelling in the acute inflammatory
phase of soft tissue disorders90. It has been shown in several animal and in vitro
studies to enhance tendon healing by stimulating collagen synthesis in tendon
fibroblasts and cell division during periods of rapid cell proliferation46, 80, 81, 107, 110.
Despite some early clinical studies advocating its benefit in the treatment of
conditions including lateral epicondylopathy13, calcific tendinopathy in the
shoulder30 and carpal tunnel syndrome31, systematic reviews and meta-analyses
have failed to show that active ultrasound is any more beneficial than placebo for
the treatment of soft tissue disorders including tendinopathy16, 87, 108.
Diagnostic ultrasonography is, however very useful as a diagnostic tool in the
assessment of Achilles tendinopathy and to guide other treatments, such as
these assorted injection therapies.
Dry needling, autologous blood and platelet-rich plasma injections

Dry needling (or barbotage) is the repeated lancing of an abnormal area of
tendon in order to incite internal haemorrhage. Autologous blood injections
have been used in the management of tendinopathies to provide cellular and
humoral mediators to promote healing in areas of degeneration. Platelet-rich
plasma (PRP) contains a more concentrated amount of platelets than whole
blood with higher concentrations of growth factors.
Studies have evaluated autologous blood injections in lateral25, 32 and medial102
epicondylopathy as well as patella tendinopathy47. All report good clinical results
in terms of pain scores in patients who had not responded to other forms of non-
operative intervention. All of these studies are relatively small case series, and do
17
not include any controls, with three studies by the same group.
Aspenberg and Virchenco showed that a single injection of platelet concentrate
significantly improved Achilles tendon repair strength, stiffness and energy
absorption compared to controls in rats at 8, 11, 14, 21 and 28 days after surgical
division of the tendon9. They later showed that the beneficial effects of the
platelet concentrate were not present when mechanical stimulus was removed
by injecting the rat calf muscles with botox109.
A pilot study evaluating patients with refractory lateral epicondylopathy, which
did include a control group, found significantly better clinical results after a single
PRP injection. There was a 60% improvement in the visual analogue pain scores
in the study group compared to only a 16% improvement in control subjects
who received an injection of bupivacaine (p = .001)64.
PRP contains high concentrations of growth factors including; platelet-derived
growth factor, transforming growth factor beta, epidermal growth factor and
Insulin like growth factors amongst others. These cytokines initiate intracellular
signalling resulting in the expression of proteins responsible for cellular
chemotaxis, matrix synthesis, and proliferation65. It is thought that repair of the
degenerative tissue in tendinopathy may be stimulated by introducing supra-
physiological concentrations of these growth factors.
The early results of autologous blood and especially PRP injections in other areas
of the body are encouraging but they provide a poor level of evidence and there
are no studies pertaining to Achilles tendinopathy. The basic science behind the
mechanism of action of PRP is interesting, but so far the studies have produced
more questions than answers as to its role in tendinopathy and tendon healing.
More information from good quality scientific and clinical research is required
before these can be recommended as first line treatments.
High volume injections

Chan et al19 reported that high volume injections of up to 40 mL of saline
significantly reduced pain and improved function in patients with chronic
Achilles tendinopathy who had failed an eccentric strengthening program. They
hypothesised that high volumes normal saline would produce local mechanical
effects causing neovessels to break or occlude and that neural ingrowth
accompanying the neovessels would also be damaged, decreasing the amount
of pain perceived. They also injected 25mg of hydrocortisone into each of the
patients however which may have affected their results. This method of treatment
has yet to be repeated elsewhere, and the hypotheses as to the mechanism of
action have yet to be investigated. There was also no control group in this small
study, therefore the evidence for this treatment modality is minimal, although it
appears that it ‘does not burn bridges’.
Intratendinous injection of hyperosmolar dextrose

Hyperosmolar dextrose has been used as part of prolotherapy regimes for the
treatment of chronic tendon pain since as early as the 1940s. The injected solution
16
is said to initiate a local inflammatory response, causing fibroblast proliferation

and subsequent collagen production, resulting in increased tendon strength
although the evidence for this is scant. Using a modification of this technique,
Maxwell et al. performed intratendinous injections of hyperosmolar dextrose
under ultrasound guidance, targeting the abnormal anechoic and hypoechoic
areas in the tendon. Their uncontrolled pilot study showed a significant reduction
in tendon pain at rest and during tendon-loading activities60.
Well conducted prospective randomised controlled studies, however, are still
lacking85.
Low-dose heparin
Low-dose heparin has been used in the management of Achilles tendinopathies,
with the aim of limiting the formation of adhesions. However, there is some
evidence that there is no beneficial effect62 and it has even been suggested that
heparin, in itself, can cause degenerative tendinopathy in rats104.
Aprotinin
Of all the alternative substances available for injection aprotinin was once
the most popular85. Aprotinin is a broad-spectrum protease (including matrix
metalloproteinase (MMP)) inhibitor. It was initially indicated for use in open heart
and liver surgery to reduce blood loss. Proponents of aprotinin in tendon disorders
suggest that by inhibiting the enzymes that break down or degrade tendons the
healing response may be promoted. The clinical results of aprotinin injections
have been conflicting with a PRCT by Brown et al failing to show any statistically
significant benefit over placebo17. There was no mention of a power analysis in
this paper however therefore it may have been that there was an insufficient
sample size to detect such a benefit. The same group of authors subsequently
reported successful treatment of non-insertional Achilles tendinopathy in a non-
randomised study74.
The debate over the use of this drug is now purely academic as it was temporarily
withdrawn worldwide in 2007 after studies suggested that its use increased the
risk of complications or death. This was confirmed by follow-up studies and it
was entirely and permanently withdrawn in May 2008, except for very restricted
research use.
17
Sclerosing therapy
Sclerosing therapy for chronic Achilles tendinopathy is based on the premise

that the process of neovascularization in the damaged tendon is the source
of the patient’s pain2, 69. Studies in the European literature have implicated
neurovascularization as possible pain generators in Achilles tendinopathy,
possibly because of the sensory nerves linked to the vessels2, 69, 73. These findings
led to the hypothesis that destruction of the vessels and nerves would lead to
pain relief2, 5, 6, 24, 56, 69-71, 73, 111. A sclerosing agent, Polidocanol (not FDA approved), is
injected under ultrasound and color Doppler guidance into the neovascularization
area outside the tendon. Reports of this treatment are retrospective case series
(level IV evidence) with relatively short follow-up5, 6, 56, 70, 71, 111. The largest series
in these retrospective reports included 42 tendon injections, 38 (90%) of which
were reported to be successful at 2-year follow-up56. The only “comparative”
studies had small numbers of patients5, 6. Injections of Polidocanol in 10 patients
(group A) were compared to injections of Lidocaine in 10 patients (group B)5.
At 3-month follow-up, 5 of the 10 patients in group A were satisfied with their
results, while none of the 10 patients in group B reported any pain relief. Another
report from the same group compared Polidocanol injections (10 patients) to
open revision of the neurovascular area outside the tendon (10 patients)6. At
3-month follow-up, 8 of 10 patients with surgery and 6 of 9 patients (one patient
lost to follow-up) with injection had good results; at 12-month follow-up, all 10
patients with surgery and 6 of 9 with injection had good results. In the most
recent report, 52 tendons in 48 patients were treated with sclerosing therapy111.
At 14-month follow-up, 37 (71%) patients had good results, but after additional
injections all 52 patients were considered satisfactory. Reports of this therapy
describe an absence of neovascularization in all patients with pain relief, as well
as a decrease in tendon thickness and a “more normal” appearance of the tendon
on ultrasound.
Although the FDA listed as known adverse events related to Polidocanol, DVT,
necrosis and ulceration at the treatment site, and reversible cardiac arrest,33
Alfredson2 reported only two complications that “possibly might be related” to
sclerosing therapy in 150 Achilles tendons: one total Achilles tendon rupture and
one partial rupture.
In a recent systematic review of the literature concerning nonoperative
management of midportion Achilles tendinopathy, Magnussen et al.59 reported
that eccentric exercises had the most evidence of effectiveness in management
of midportion Achilles tendinopathy. They suggested that sclerotherapy might
prove to be a beneficial alternative treatment if other authors can demonstrate
success similar to that reported by Alfredson et al.; however, because less invasive
eccentric exercises have been shown to decrease neovascularization with low
risk and low cost, sclerosing injection therapy probably should be reserved for
those who fail or are not capable of eccentric exercises. Obviously, additional
data obtained from larger randomized comparative studies are needed before
sclerosing therapy can be considered a first-line management for Achilles
tendinopathy.
16
Electrocautery
Electrocautery is another method of dealing with the neovascularisation in

the tendon which may be responsible for the pain associated with Achilles
tendinopathy.
Only one, non-controlled study of 11 patients has investigated the effect of colour
Doppler ultrasound-guided electrocoagulation in the management of painful
chronic mid-portion Achilles tendinopathy15. At six months follow up, reduced
pain during rest and activity was observed in 10 of the 11 patients. There were no
side effects or complications reported. The hyperaemia in the tendon reappeared
two weeks after treatment in all patients and persisted throughout the follow up
period. The authors suggested that this indicated that other mechanisms, such
as the destruction of nerves accompanying the vessels were responsible for the
observed pain relief.
The clinical and basic science evidence base for this treatment is therefore in
its infancy and much more research is required before this treatment may be
recommended.
Deep Friction massage
Deep transverse friction massage (DTFM) has been the subject of a Cochrane
review. There were only two randomized controlled trials of sufficient quality to
be included, neither of which evaluated its use in Achilles tendinopathy. In neither
trial did DTFM show a consistent benefit over the control group for pain, strength
or functional status. All of the studies evaluated were of insufficient statistical
power. There is therefore no good evidence to recommend this treatment in
Achilles tendinopathy.
Conclusions
Conservative management of non-insertional Achilles tendinopathy must be

considered to be the mainstay of treatment. Several conservative approaches
have shown success in this condition. Eccentric strengthening should be
considered as the first line option, as it has the most evidence for its effectiveness,
no special or expensive equipment is required, and there appears to be no risk
associated with it. An 8-year follow-up study found that, overall, non-operative
treatment was unsuccessful in only 29% of patients with acute to subacute
Achilles tendinopathy75. For a small proportion of patients, surgery may be
necessary.
17
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16
Management of Tendinopathy of the Main Body of the Achilles Tendon: Exercise
“Use it or lose it ”
(Jimmy Connors)
Chapter 10.
Management of
Tendinopathy of the Main
Body of the Achilles
Tendon: Exercise
Karin G. Silbernagel, Karim Khan, Roland Thomeé, Jón Karlsson
Take Home Message
• Patients with Achilles tendinopathy should receive rehabilitation exercises as

their initial treatment.
• To experience a favorable outcome from exercise, the exercises are allowed to
cause pain and should be performed daily. The use of a pain-monitoring model
aids the clinician and patient in the balance between overloading and loading
enough to achieve a positive response to the exercises.
• The exercise program needs to continue for at least 12 weeks, but more often
needs to be continued for up to a year.
Introduction
We review the effects of exercise and mechanical loading on the Achilles tendon.
We also review the different exercise programs described and recommended in
the literature for patients with tendinopathy in the mid-portion of the Achilles
tendon. Patients with Achilles tendinopathy should initially be treated with an
exercise program for three to six months before other management methods are
17
considered1, 28, 46. The goal of the exercise program for Achilles tendinopathy is to
promote healing of the tendon as well as to improve strength, endurance and
function12, 68, 71. There is, however, still a debate as to how the exercise program
should be designed3, 12, 43, 51, 56, 61, 67, 76. The most debated topics are whether
the program should contain only eccentric exercises, or concentric/eccentric
exercises or a combination of exercises. Another debated topic is whether the
program should allow for pain during and after exercise. Furthermore, the
optimal number of repetitions in each session, the optimal frequency of sessions
per week, and the optimal progression of the exercise program are not known.
There is also a debate on how long to proceed with the exercise program prior to
trying other types of treatments.
Effect of exercise on tendons
The adaptive responses of tendons to exercise are slower than those seen in
muscles. Improvements may take several months, but can, nonetheless, be
considerable over time. Animal studies indicate that the tendon is positively
affected by physical exercise by becoming larger, stronger and more resistant
to injury16, 27, 30. Tendons increase their tensile strength, stiffness and total
weight with exercise30. Growing animals have a better response to exercise than
mature animals27, 30. The difference appears to be that growing animals respond
by increasing the size and weight of tendons, whereas the mature animals
respond by improving the structure of the tendon with exercise30. The human
Achilles tendon has not been studied to the same degree as animal tendons,
but Magnusson & Kjaer48 found that intensively trained athletes had a greater
cross-sectional area of the Achilles tendon compared with controls. The Achilles
tendon in athletes subjected to intermittent high loads (such as volleyball
players) and athletes subjected to repetitive loading (such as runners) also has
a larger cross-sectional area than a comparable control tendon33. It is, however,
not clear whether the results from these two studies48, 33 are an effect of training
or a natural selection. Hansen and co-workers24 did not find any increase in the
cross-sectional area of the Achilles tendon after 9 months of regular running in
previously untrained individuals.
Recent studies also indicate that tendon tissue adaptation to mechanical loading
differ between men and women52, 75. One research group47 has reported that
women have:
• A lesser degree of tendon hypertrophy response to habitual training

• A lower tendon collagen synthesis rate following acute exercise
• The rate of collagen synthesis is affected by estradiol levels
• A lower mechanical strength of tendon
Measurements using microdialysis in the human Achilles tendon show an

acute effect in response to both isometric and dynamic exercise, with increased
blood flow in the peritendinous region15, 34. A study of collagen turnover, using
16
microdialysis, showed that an acute bout of exercise increased the collagen

synthesis of type I collagen 72 hours after exercise39. Further studies by the same
researchers have shown that the synthesis of collagen peaks three days after
the run and returns to normal levels after five days after a marathon run38. The
long-term effects of heavy daily exercise (2-4 hours per day) showed an increase
in collagen synthesis at week four, with continued elevated levels at week 1137.
Collagen degradation, on the other hand, was also elevated at week four, but had
returned to a normal level at week 11. The net positive effect on the tendon of
this type of physical activity might thus not appear until later, in this case not until
after 11 weeks. This is in agreement with our clinical experience that numerous
patients with mid-portion Achilles tendinopathy describe noticeable effects
from rehabilitation exercises, with clinically relevant changes in symptoms and
function, after approximately 8-12 weeks of rehabilitation. A study of the Achilles
tendon in guinea fowl showed that treadmill endurance training changed the
mechanical properties of the tendon but did not cause tendon hypertrophy16.
The authors suggested that the Achilles tendon responds to repeated stress by
improving its capacity to withstand mechanical fatigue, but that this does not
necessarily enable the tendon to withstand higher loads. The training specificity
might therefore be of great importance in relation to the tendon’s response
to exercise. This can be one explanation for the positive effects from strength
exercises seen in several studies on Achilles tendinopathy4, 7, 45, 55, 63, 69 even though
the patient is an active endurance athlete involved in running and jumping.
One also has to remember that overloading of the Achilles tendon through
physical exercise without appropriate time for recovery is suggested as the main
pathological stimulus in overuse damage to the tendon27, 28, 41, 57. Kjaer32 suggests
that a load of a certain magnitude, together with elongation of the muscle-
tendon unit promotes the increased reorganization and synthesis of collagen.
Effect of immobilization on tendons
Immobilization has basically the opposite effect from that seen in exercise and
loading27, 30. Immobilization causes tendon atrophy, and collagen fibers become
thinner and more disoriented, a negative effect on the quality of the tendon
structure30. Immobilization also has negative effects on the non-collagenous
tendon matrix. The tendon needs to have a certain level of force input in order
to maintain a structure in which the fibers align favorably in the direction of
physical stresses27, 30.
Effect of remobilization and reconditioning on tendons
Remobilization and rehabilitation require longer time than that needed to cause
immobilization atrophy27. It is not known whether an injured tendon can ever
completely return to its pre-injury status. Normal tendons differ from injured
tendons42. Normal tendons contain primarily type I collagen, but injured tendons
have a higher percentage of type III collagen, which is deficient in the number of
17
cross-links between and within the tropocollagen units27, 42. The tendon requires
mechanical loading in all phases of healing to recover after immobilization and
injury14, 20, 32. Also, injured and healthy tendon responds differently to exercise
- injured tendon increases collagen synthesis, but this does not occur in the
healthy tendon35. The optimal amount of loading required is, however, still
unknown20, 26, 32. The clinical challenge when treating patients with mid-portion
Achilles tendinopathy is to find the appropriate specifics with regards to exercise
prescriptions such as:
• type of exercise
• number of exercises
• amount of load
• number of repetitions per session
• number of sessions per week
• the progression of load, repetitions and sessions
• at which phase of healing is it appropriate to apply increased load?
• whether men and women should have gender specific exercise programs?
In the clinical setting, it appears important to understand, when rehabilitating

patients with Achilles tendinopathy, that tendon healing takes time and therefore
requires patience both from the patient as well as the health care professional.
Following a tendon injury, the healing process proceeds through three phases
(Figure 1) over a period of 12 months or even longer27, 28, 41.
1. Acute inflammatory phase
2. Proliferative phase
3. Maturation and remodeling phase
0 3 6 9 12
Days Months Months Months Months
Figure 1: The healing process in tendons.
16
The natural history of Achilles tendinopathy
The natural history of Achilles tendinopathy is not fully known. The short-term
(up to 12 months) prognosis following non-surgical treatment is good, with a
success rate of 50-100%7, 10, 13, 78. Angermann and Hovgaard13 reported that, at
follow-up 33-72 months after non-surgical treatment, 65% of the patients had
improved or been cured. In a recent 8-year follow-up study of patients who were
initially treated non-surgically, 94% were asymptomatic59. Twenty-nine percent
had failed to respond to non-surgical treatment and had undergone surgery.
Others report that 24-45% of patients fail to respond to non-surgical treatment
and will undergo surgery28. At 8 years, 41% of the patients developed symptoms
on the previously uninjured side59. It is, however, unclear how the non-surgical
treatment was conducted, as the above-mentioned studies omitted details of
the conservative measures implemented. The success rates for Achilles surgery
are approximately 70-80%9, 40, 54, 57, 58, 64, 72. Today, it appears that fewer patients
need surgery given the good results from well conducted exercise programs.
Exercise – general aspects
The effects of exercise training in the management of Achilles tendinopathy

appear promising, and the current consensus appears to be that all patients
should be treated with an exercise program for three to six months1, 5, 7, 13, 28, 45,
55, 63, 69
. Muscular strength, power, endurance, flexibility and motor control are
important in physical performance and exercises aimed to improve these factors
are therefore often prescribed in rehabilitation and injury prevention programs
for tendon injuries18, 25, 70. Also, patients with Achilles tendinopathy have impaired
muscle function, such as decreased strength, muscular endurance and jumping
ability on their injured side66. Impaired muscle function has also been implicated
as an etiological factor for Achilles tendinopathy8, 23, 29, 49.
Exercise is also recommended as a complement to other modalities of

management, including surgery, sclerosing injections, and medication2, 53, 58,
60, 64, 73
. Eccentric strength training is particularly effective in improving muscle
function and/or aiding in the healing process of the tendon7, 22, 63, 69, 79. There
are, however, various rationales for different types of exercises, even though
the main focus has been on the effects of eccentric training. Explanations for
successful treatment with exercise include improvement of muscular strength
and lower leg function12, 18, 55, 69, 71, repetitive stretching causing increased tensile
strength3, 7, 12, mechanical insult of pain producing nerves3, 77, blocking circulation
to the tendon3, 11, 77, mechanotransduction for enhancing tendon healing12, 14,
32, 61
, improving homogeneity of the passive structures or modulation of the
neurological stretch response12.
Exactly which type of exercise, the intensity (load), and how often it should be
performed to achieve the best outcome for patients with Achilles tendinopathy
remains debated. We review some of the exercise programs proposed in the
literature, their efficacy, and how they are used in clinical practice.
17
The eccentric exercise program
In 1984, Curwin and Stanish19 proposed an eccentric exercise program to treat

tendinitis (at that time the painful tendon injury was assumed to be due to
inflammation of the tendon). The rational for their treatment program was their
clinical finding that, in many of the athletes with “tendinitis”, eccentric loading was
somehow involved. Also, they found that the tendon pain could be reproduced in
the clinic by loading the tendon eccentrically. The rationale was that the greater
force production during eccentric activation caused a greater load in the tendon,
which was thought to promote healing, improve muscle function and reduce
pain and symptoms. To increase the load on the tendon, the program focused
on three areas: increasing the length of the tendon by stretching, increasing the
load of the tendon by using eccentric exercise and adding external weights, and
increasing the speed of muscle activation to increase the load of the tendon and
to be more sports specific.
The exercise was allowed to cause some pain but the intensity was recommended
to be at such level that only the last set of 10 repetitions should cause some pain
or discomfort. Stanish and co-workers71 reported in 1986 that in 200 patients,
who had followed their proposed eccentric exercise program for six weeks 44%
had complete relief and 43% had a marked decrease in symptoms at the 16
months follow-up. Clement and co-workers17 reported that 67% of 109 runners
with Achilles tendinitis had an excellent result with a mean recovery time of
five weeks with an exercise program that seem similar to the one described
above. Neither of these studies were, however, randomized trials, and in the
second study patients also received other treatments aimed at controlling the
inflammation, pain and biomechanical parameters.
Eccentric only exercise program
Alfredsson and co-workers7 published in 1998 a non-randomized study using a

protocol with only eccentric heel-rises with both the knee straight and the knee
bent. The treatment program (Table 1) was also supposed to be painful and,
if the exercises could be performed without experiencing any minor pain or
discomfort, the patients were instructed to increase the load by adding weights
in a back-pack.
16
Exercise Number of exercises Progression
Heel-drop – knee straight 3 sets of 15 repetitions Do exercises even if painful and

Standing on edge of step. Start 2 times/day perform until they become
with standing on the toes and 7 days a week for 12 weeks pain-free.
lower the heel all the way down. Add load until exercises again are
Get back up onto the toes by painful.
using the other leg
Heel-drop – knee bent 3 sets of 15 repetitions Do exercises even if painful and

Standing on edge of step. Start 2 times/day perform until they become
with standing on the toes and 7 days a week for 12 weeks pain-free.
lower the heel all the way down. Add load until exercises again are
Get back up onto the toes by painful.
using the other leg
Table 1: Eccentric only exercise protocol.
In the initial study7 15 patients on the waiting list for surgery were included,
and after 12 weeks they were all reported to be satisfied and back at their pre-
injury level. Since then this eccentric exercise program has been evaluated in
several studies21, 45, 56, 62, 63, 65. Most studies that have evaluated eccentric exercise
as treatment for Achilles tendinopathy report beneficial results, however, it is
difficult to compare the various studies due methodological differences31, 76.
A comprehensive treatment protocol
Since the early 1990s, our research group has used a comprehensive treatment
protocol (Table - 2) for patients with Achilles tendinopathy67-69. This program
is based on the proposal by Curwin & Stanish19 that the load of the tendon is
increased by both increasing the external weight and increasing the speed of
movement. The program includes both concentric and eccentric exercises of the
calf musculature (Figure 2). The reason for this is that concentric and eccentric
activations are included in all physical activities and that patients with Achilles
tendinopathy have deficits in both concentric and eccentric strength66. The
exercise program, complemented with a pain-monitoring model described
below, was tested in two randomized controlled trials and led to significant
improvements in patients with Achilles tendinopathy67, 69.
17
Phase 1: Week 1-2

Patient status: Pain and difficulty with all activities, difficulty performing 10 one-legged toe-raises
Goal: Start to exercise, understanding nature of their injury and of pain monitoring model
Treatment program: Perform exercises every day
• Pain monitoring model information and advice on exercise activity
• Circulation exercises (moving foot up/down)
• Two-legged toe-raises standing on the floor (3x10-15)
• One-legged toe-raises standing on the floor (3x10)
• Sitting toe-raises (3x10)
• Eccentric toe-raises standing on the floor (3x10)
Phase 2: Week 2-5

Patient status: Pain with exercise, morning stiffness, pain when performing toe-raises
Goal: Start strengthening
Treatment program: Perform exercises every day
• Two-legged toe-raises standing on edge of stair (3x15)
• One-legged toe-raises standing on edge of stair (3x15)
• Eccentric toe-raises standing on edge of stair (3x15)
• Quick rebounding toe-raises (3x20)
Phase 3: Week 3-12 (or longer if needed)

Patient status: Handle the phase 2 exercise program, no pain distally in tendon insertion, possibly decreased
or increased morning stiffness
Goal: Heavier strength training, increase or start running and/or jumping activity
Treatment program: Perform exercises every day and with heavier load 2-3 times per week
• One-legged toe-raises standing on edge of stair with added weight (3x15)
• Eccentric toe-raises standing on edge of stair with added weight (3x15)
• Plyometrics training
Phase 4: Week 12-6 months (or longer if needed)

Patient status: Minimal symptoms, not morning stiffness every day, can participate in sports without difficulty
Goal: Maintenance exercise, No symptoms
Treatment program: Perform exercises 2-3 times per week
• One-legged toe-raises standing on edge of stair with added weight (3x15)
• Eccentric toe-raises standing on edge of stair with added weight (3x15)
Table 2: Comprehensive treatment protocol.
16
Circulation Two-legged toe-raise One-legged toe-raise

exercise standing on the floor standing on the floor
Eccentric toe-raise Two-legged toe-raise One-legged toe-raise

standing on the floor standing on the floor standing on a step
Eccentric toe-raise Sitting toe-raise Quick rebounding

standing on a step toe-raise
Figure 2: The exercises included in the treatment protocol.
Pain-monitoring model
The exercise program used in the comprehensive treatment protocol for Achilles
tendinopathy allowed the patient to experience pain during and after exercise.
By using a pain monitoring model (Figure 3), patients can be guided in how to
deal with the pain. Curwin & Stanish19 described that some pain and discomfort
is allowed, and proposed to increase the load as soon as the exercise was pain
free. Our clinical experience is that patients are often afraid to perform physical
activities that cause pain in the Achilles tendon from fear of further injury or a
total Achilles tendon rupture. This fear often prevents the patients from loading
the Achilles tendon sufficiently to cause meaningful adaptive positive changes
in the tendon. The pain-monitoring model is used to facilitate the patients’
understanding of the amount of pain allowed during and after exercise. The
model was initially developed by Thomeé and presented in a randomized
controlled trial in 1997 for patients with patellofemoral pain syndrome74. The
pain-monitoring model is a tool that also helps the clinician and patient to
determine how the exercise program should progress.
17
Pain Monitoring Model
Visual Analog Scale - VAS
Acceptable Zone High Risk Zone
0 5 10
No pain Worst pain
imaginable
1. The pain was allowed to reach 5 on the VAS during the exercises
2. The pain after the whole exercise programme was allowed to reach 5 on the
VAS but should have subsided the following morning.
3. Pain and stiffness in the Achilles tendon was not allowed to increase from
week to week.
Figure 3: Pain-monitoring model.
Eccentric training reviews
A systematic review by Kingma and co-workers31 on eccentric overload training

in patients with Achilles tendinopathy included nine studies6, 7, 21, 45, 55, 63, 65, 69,
71
(three randomized controlled trials and six controlled trials). In six6, 7, 21, 45,
63, 65
of those studies, only eccentric training was used; in the other three55, 69,
71
, the program combined eccentric training with other interventions, such as
stretching and ice. The duration of the exercise programs were six or 12 weeks.
Kingma and co-workers31 concluded that the effect of eccentric exercise appeared
promising, but no definite conclusions could be drawn due to methodological
shortcomings. In a recent systematic review46 on non-operative treatment for
mid-portion Achilles tendinopathy, five prospective randomized trials were
identified where eccentric exercise was compared to controls45, 50, 55, 62, 69. Four of
these trials showed statistically significant improvement in pain scores in the
eccentric groups compared with control groups, whereas one trial showed no
significant difference. In summary, they reported that 60% to 90% of the patients
reported significant improvement in patient satisfaction and decreased pain
with eccentric exercise. They concluded that there is currently more evidence
in support of eccentric exercise than other interventions such as extracorporeal
shockwave therapy, local steroid therapy, sclerosing injections, deproteinized
hemodialysate and topical glyceryl nitrate application.
16
Eccentric compared to concentric exercise
Despite the numerous studies on eccentric exercise programs, only two trials
compared eccentric training to concentric training in patients with Achilles
tendinopathy 45, 55. In both these studies, the group that received eccentric
treatment had a significantly greater improvement compared to the concentric
group. The concentric treatment groups, however, also had, significant
improvements. In these two studies, the eccentric and concentric exercise groups
were not comparable in regards to load or training volume36, 45, 55. Interestingly,
Rees and co-workers 61 compared concentric and eccentric loading in the
Achilles tendon and found no differences in peak tendon force or tendon length
between the two exercises. They found, however, a high-frequency oscillation
in the tendon force with eccentric loading which was not found with concentric
loading. The importance of the oscillation for tendon healing is not known. Thus,
there is a need for further studies on the mechanism of the effect of eccentric
training as well as studies comparing eccentric training with other exercise
protocols. However, we believe it is safe to conclude that concentric exercise, if
heavily loaded, can have a positive effect on patients with Achilles tendinopathy,
and most certainly will not have a negative effect.
Other aspects that might affect the outcome of treatment
As stated before the natural history of Achilles tendinopathy is not fully known.
There are also various responses to exercise treatment in different studies where
the reported success rate ranges from approximately 60% to 90%31, 44. The wide
variations found both in research and in the clinic might be due to the diversity
of the patient population whereas the exercise program used are normally very
standardized. It can also be seen when comparing various research studies that
there is a range of follow-up times31, 46. Since a tendon takes up to a year to improve,
it might not be feasible to expect that 12 weeks of rehabilitation is enough, and
the patient might continue to improve during this time. Studies have shown a
continued improvement over time up to a year63, 67, 69. The individual patient’s
activity level, health status, previous injuries and attitude towards exercise might
very well influence the outcome of the rehabilitation. Furthermore, research
indicates that a tendon’s response to mechanical loading varies with age and
gender. Further studies are needed to determine the effect of exercise, and in
future it might be important to evaluate different subgroups separately and to
perform long-term follow-ups to receive answers in regards to how to develop
and implement exercise as treatment successfully.
Conclusion
Patients with Achilles tendinopathy should receive rehabilitation exercises as

their initial treatment. To experience a favorable outcome from exercise, the
exercises are allowed to cause pain and should be performed daily. The use of
17
a pain-monitoring model aids the clinician and patient in the balance between
overloading and loading enough to achieve a positive response to the exercises.
The exercise program should consist of eccentric exercises but also exercises such
as concentric strengthening and other exercise to address possible functional
deficits. The exercise program needs to continue for at least 12 weeks, but more
often needs to be continued for up to a year.
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17
16
Ultrasound and Doppler-Guided Sclerosing Polidocanol Injections for Treatment of the Chronic Painful Tendon
“One of the greatest pains to human

nature is the pain of a new idea”
(Walter Bagehot 1826-1877)
Chapter 11.
Ultrasound and Doppler-

Guided Sclerosing
Polidocanol Injections
for Treatment of the
Chronic Painful Tendon
Håkan Alfredson
Take Home Message
1. Use ultrasound and Doppler-guided technique.

2. Use small volumes (1-2 ml per treatment session) of polidocanol. Polidocanol
can travel in the tissue, and when injecting especially in the Achilles midportion
region, excessive volumes can result in thrombosis of multiple minor veins caus-
ing major local swelling. The substance can hit communicant veins and cause
thrombosis.
3. Make sure polidocanol is not injected into a tendon. Intra-tendinous injection
can cause local necrosis and lead to a partial tendon rupture.
Introduction
Chronic tendinopathy is well known to be difficult to treat. However, new research

findings have helped us to better understand where the pain comes from,
and based on these findings a new treatment method, sclerosing polidocanol
injections, have been introduced.
Recent research findings, using gray scale ultrasound (US) and Colour Doppler
(CD), and immunohistochemical analyses of tendon tissue biopsies, have
17
confirmed the presence of high blood flow/neovessels juxtapositioned to

nerves in chronic painful Achilles and patellar tendinosis. Few nerves were
found inside the tendon, but multiple nerves outside the tendon, especially on
the deep surface of the tendon. These nerve fascicles contain sympathetic and
sensory fibers. Treatment with ultrasound and Doppler-guided injections of the
sclerosing substance Polidocanol, targeting the region with high blood flow/
neovessels (and nerves) outside the tendon, have shown good clinical short-
and mid-term results in patients with chronic painful midportion Achilles and
proximal patellar tendinopathy. Remodeling of successfully treated Achilles
tendons has been demonstrated.
Background
At the Sports Medicine Unit in Umeå, Sweden, there has during the last fifteen
years been intensive research on pain mechanisms related to the chronic
painful tendon. Investigations using gray-scale ultrasound (US) together with
colour Doppler (CD) have shown that chronic painful non-insertional Achilles
tendinopathy had high blood flow most often in the regions with structural
tendon changes, while pain-free normal tendons had no high blood flow10. The
structural tendon changes were located mainly in the ventral Achilles tendon,
and the blood flow was seen mainly in regions with structural changes, and in
the soft tissue just outside the ventral tendon.
These findings led to evaluation of pain in relation to the regions with high blood
flow just outside the ventral tendon. US+CD-guided injections of small volumes
of a local anaesthetic, targeting only the regions with high blood flow on the
ventral side of the tendon (just outside the tendon), led to complete pain relief
during tendon loading activity. The results from parallel studies on biopsies,
immunohistochemical analyses, demonstrated nerves in close relation to blood
vessels1.
Methods
The findings using US+CD, immunhohistochemical analyses of biopsies, and

injections of local anaestesia, led to the hypothesis that blood vessels and nerves
on the ventral side of the Achilles tendon were of significant importance for the
tendon pain. Methods to interfere with blood vessels and nerves were discussed,
and we decided to try US+CD-guided injection treatment of the sclerosing
substance polidocanol. Polidocanol is a well known substance, that has been in
use for many years to treat varicose veins and teleangiectasies, with very few
side effects6,7. Polidocanol has a sclerosing effect (primarily acting on the intima
layer in the vascular wall), and a local anaesthetic effect. The active substance
is an aliphatic non-ionized nitrogen-free surface anaesthetic. It was decided to
start with a pilot study on patients with a long duration of pain symptoms from
chronic midportion Achilles tendinosis, and to use the lowest concentration (5
mg/ml) of polidocanol.mg/ml) of polidocanol.
16
Rehabilitation after treatment
We hypothesized that in chronic painful tendinopathy, the tendons are not

weak, but rather strong, painful tendons. Consequently, we believe that these
tendons can be loaded relatively early after treatment. However, there are
individual variations between patients, and long periods of inactivity with signs
of muscle atrophy need to be considered before heavy tendon loading activity
is instituted. In our experience it is very rare that there are signs of muscle
atrophy and dysfunction not enabling them to follow our traditional early
loading rehabilitation plan. Also, a minor study using functional tests before
and after total pain relief with UD+CD-guided injection of a local anaestetic,
showed normalized functional tests after application of local anaesthesia (non
published material). The rehabilitation after polidocanol injections was initially
very aggressive, and full tendon loading was allowed within the first week after
treatment. However, we have seen that initially after the injections there is an
increased intra-tendinous blood flow (secondary to the treatment outside the
tendon), and we have the impression that a certain period with lower tendon
load is needed for the tendon to adapt to the changes induced by the treatment.
Consequently, we have changed the protocol to include a 2-week period with
lower tendon loading activity before full loading is instituted. Our traditional
rehabilitation protocol after polidocanol injection treatment is as follows:
- Day 1: Rest-very light Achilles tendon loading.
- Day 2-7: Range of motion exercises and short walks in slow tempo.
- Day 8-14: Longer walks, light bicycling.
- After 14 days: Gradual return to previous (before injury) tendon loading
activity.
Follow-up treatment
6-8 weeks after each injection treatment a new clinical and US+CD examination
is performed. If there is remaining tendon pain during loading, together with
remaining high blood flow on the deep side of the tendon, another injection
treatment is performed-followed by the same rehabilitation protocol as after the
first injection treatment. If there is no tendon pain, but remaining high blood
flow on (outside and inside) deep side of the tendon, no injection treatment
is performed. Important: Injection treatment should only be instituted for the
combination of tendon pain and high blood flow on (outside and inside) the
deep side of the tendon. We recommend a maximum of 5 injection treatments,
with 6-8 weeks in between. The reason we wait 6-8 weeks for follow up is that
there is sometimes a delayed response to the treatment, and also that the
increased intra-tendinous blood seen initially after treatment (secondary to the
injection) can possibly be misinterpreted as being remaining high blood flow
and leading to another injection treatment. After 6-8 weeks the elevated intra-
tendinous blood flow (secondary to the injection) is most often normalized.
17
Clinical studies
A pilot study on 10 patients (7 males and 3 females, mean age 55 years) with
chronic painful midportion Achilles tendinosis11. US+CD-guided injections of
polidocanol (5 mg/ml), injected in small fractions (0.1-0.2 ml per site-maximum
of 2 ml in total), targeting the regions with high blood flow outside the ventral
tendon (Figure 1).
Figure 1: Patient with chronic painful midportion Achilles tendinopathy. Gray-scale

ultrasound (longitudinal view) demonstrating thickening of Achilles midportion,
including minor structural changes and hypo-echoic regions. Colour Doppler shows
high blood flow (neovascularisation-colored structures) from ventral side of tendon
into regions with structural changes and hypo-echoicity.
Injection of polidocanol targeting the region with increased blood flow outside the
ventral tendon.
After a mean of 2 polidocanol injection treatments, with 6-8 weeks in between,

8/10 patients were satisfied with the effect of the treatment and back to full
Achilles tendon loading activity. At the 6 months follow-up, the same 8 patients
were still satisfied, their mean VAS (Achilles tendon pain during loading) had
decreased significantly from 73 before treatment to 8 after treatment, and there
was no remaining high blood flow (neovascularisation) in the tendons. The two
patients who were not satisfied (remaining tendon pain) had remaining high
blood flow in the tendons.
A double-blind randomized controlled study was performed on patients with
chronic painful midportion Achilles tendinosis2. The effects of US+CD-guided
polidocanol injections were compared with the effects of US+CD-guided
lidocaine+Adrenalin injections. The results showed that there was only a
16
temporary effect of the lidocaine+Adrenalin injections, but 8/10 patients

were satisfied and back in full Achilles tendon loading activity after a mean
of two polidocanol (10mg/ml) injection treatments. We concluded that local
anaesthesia+Adrenalin in the target region was not enough for good clinical
effects, but polidocanol seem to have the effects required for good clinical
outcome.
Increased patient material allowed for follow-ups of larger groups. In a 2-year
follow-up study (clinical and US+CD) of 42 patients (23 men and 19 women, mean
age 53 years), 38 patients were still satisfied with the results of the treatment,
and their VAS during Achilles tendon loading activity had decreased from 75
before treatment to 7 at follow-up8. Ultrasound showed a significant reduction
in the mean midportion tendon thickness (from 10 mm to 8 mm, p<0.05) and a
“more normal” structure. CD showed no, or a few, regions with remaining high
blood flow (neovessels) in the majority of the successfully treated tendons, while
there were multiple regions with high blood flow in the not satisfied patients. We
concluded from this follow-up study that initially good clinical results seemed
to lead to remaining good clinical results in the majority of the patients. Also,
ultrasound showed a decreased tendon thickness and improved structure 2
years after treatment, indicating a remodeling-regenerating potential8.
We discussed whether the differences in clinical results depended on the
concentration of the polidocanol, and hypothesized that a higher concentration
of polidocanol could lead to a faster clinical improvement. In a randomized study
on patients with chronic painful midportion Achilles tendinosis, performed by
our collegues at the Capio Arthro Clinic in Stockholm, the effects of US+CD-
guided polidocanol injections in the concentrations of 5mg/ml and 10mg/
ml were compared9. The results showed around 70% satisfied patients in both
groups, and no significant differences in the number of injections or volumes
given, between patients treated with 5 or 10 mg/ml polidocanol.
Also others have shown good clinical results with US+CD-guided injections of
polidocanol. Clementsson et al. (2008) showed good or excellent results in 20/26
midportion Achilles tendinosis tendons4.
Complications using sclerosing polidocanol injection treatment
At our clinic, patients undergoing this treatment are followed closely, and many
are involved in research projects with long follow up periods. All patients have
been given complications related to the treatment. Therefore, we believe that
we have reliable information about the complication rate in our material. After
more than 1000 treated tendons, at the Sports Medicine Unit in Umeå and at the
Capio Artro Clinic in Stockholm, we have registered 6 total and 2 partial Achilles
tendon ruptures, and 1 partial patellar tendon rupture. We believe this is a low
complication rate. Also, it needs to be remembered that we use return to full
tendon loading activity already 2 weeks after treatment, and we don’t use a
specific functional training program after treatment.
17
Pitfalls
Although we have very few complications in our material, we have been informed
about complications experienced by others. Complications such as thrombosis in
the lower leg, excessive swelling around the Achilles and partial Achilles tendon
rupture have been reported.
To try to avoid complications we strongly suggest the following recommendations
are used:
- Follow the published method description.

- Use ultrasound and Doppler-guided technique.
- Use small volumes (1-2 ml per treatment session) of polidocanol.
Polidocanol can travel in the tissue, and when injecting especially in the
Achilles midportion region, excessive volumes can result in thrombosis
of multiple minor veins causing major local swelling. The substance can hit
communicant veins and cause thrombosis.
- Make sure polidocanol is not injected into a tendon. Intra-tendinous
injection can cause local necrosis and lead to a partial tendon rupture.
- Make sure that polidocanol is not injected into a joint. Injection into a joint
can cause synovitis and fibrosis.
Recent findings of relevance-Immunohistochemistry
Biopsies from patients with chronic painful midportion Achilles tendinosis have
shown that the ventral paratendinous tissue is under marked influence of the
nervous system, including sympathetic and sensory nerves. There are relatively
few nerves inside the tendon, but especially outside the ventral tendon there are
multiple nerve fascicles, containing sensory (SP, CGRP) and sympathetic nerve
fibers, located in close relation to large and small arteries3.
Conclusions
Ultrasound and Doppler-guided injections of the sclerosing substance

polidocanol, targeting the region with high blood flow and nerves outside the
chronic painful Achilles tendon has been shown to give good pain relief and
allow for a return to tendon loading activities. After treatment, a relatively fast
return to tendon loading activities, without any specific functional training, has
been instituted. Very few complications have been registered, possibly indicating
that the tendinopathy tendon is a strong tendon. Also, for midportion Achilles
tendinopathy, a remodeling and possibly a regeneration has been demonstrated
on ultrasound follow-ups.
16
References
1. Alfredson H, Öhberg L. Forsgren S. Is vasculo-neural ingrowth the cause of pain in chronic Achilles
tendinosis?-An investigation using ultrasonography and colour Doppler, immunohistochemistry,
and diagnostic injections. Knee Surg, Sports Traumatol, Arthrosc 2003; 11 :334-8.
2. Alfredson H, Öhberg L. Sclerosing injections to areas of neovascularisation reduce pain in chronic
Achilles tendinopathy: A double-blind randomized controlled trial. Knee Surg, Sports Traumatol,
Arthrosc 2005; 13: 338-44.
3. Andersson G, Danielsson P, Alfredson H, Forsgren S. Nerve-related characteristics of ventral
paratendinous tissue in chronic Achilles tendinosis. Knee Surg, Sports Traumatol, Arthrosc 2007;
15:1272-9.
4. Clementson M, Lorén I, Dahlberg L, Åström M. Sclerosing injections in midportion Achilles
tendinopathy: a retrospective study of 25 patients. Knee Surg Sports Traumatol Arthrosc 2008; 16:
887-90.
5. Conrad P, Malouf GM, Stacey MC. The Australian polidocanol (aethoxysklerol) study. Results at 2
years. Dermatol Surg 1995; 21: 334-6.
6. Guex JJ. Indications for the sclerosing agent polidocanol. J Dermatol Surg Oncol 1993; 19: 959-961.
7. Khan, K.M., Cook, J.L., Bonar, F., Harcourt, P., Åström, M. Histopathology of common tendinopathies.
Update and implications for clinical management. Sports Med 1999; 27: 393-408.
8. Lind B, Öhberg L, Alfredson H. Sclerosing polidocanol injections in mid-portion Achilles tendinosis:
remaining good clinical results and decreased tendon thickness at 2-year follow-up. Knee Surg, Sport
Traumatol, Arthrosc 2006; 14: 1327-32.
9. Willberg L, Sunding K, Öhberg L, Forsblad M, Fahlström M, Alfredson H. Sclerosing injections
to treat midportion Achilles tendinosis: a randomised controlled study evaluating two different
concentrations of Polidocanol. Knee Surg Sports Traumatol Arthrosc. 2008; 16: 859-64.
10. Öhberg L, Lorentzon R, Alfredson H. Neovascularisation in Achilles tendons with painful tendinosis
but not in normal tendons: an ultrasonographic investigation. Knee Surg Sports Traumatol, Arthrosc
2001;9: 233-8.
11. Öhberg L, Alfredson H. Ultrasound guided sclerosis of neovessels in painful chronic Achilles
tendinosis: pilot study of a new treatment. Br J Sports Med 2002; 36: 173-7.
12. Öhberg L, Alfredson H. Sclerosing therapy in chronic Achilles tendon insertional pain-results of a
pilot study. Knee Surg, Sports Traumatol, Arthrosc 2003; 11:339-43.
17
Conservative Management of Tendinopathy of the Main Body of the
Achilles Tendon with High Volume Image Guided Injection (HVIGI)
“A simple Strip to normal”
(Otto Chan)
Chapter 12.
Conservative Management
of Tendinopathy of the
Main Body of the
Achilles Tendon with High
Volume Image Guided
Injection (HVIGI)
Otto Chan, Tom Crisp, Nat Padhiar, John B. King, Nicola Maffulli
Take Home Message
• Image guided peritendinous injections are preferable to intratendinous or

“blind” injections.
• High Volume Image Guided Injections (HVIGI) is a safe and novel technique with
excellent results.
• Post-injection Eccentric Rehabilitation Programme (PIERP) is essential.
Introduction
Peritendinous and intratendinous injections have been performed, both blind

and image guided and numerous agents have been used. Low dose heparin has
23
been used in the management of peritendinous and intratendinous pathology

but an experimental study showed increased tendon degeneration in rats given
intratendinous injection of heparin17. Peritendinous injection of corticosteroids
remains controversial. A randomized controlled trial found that peritendinous
injection of methyl prednisolone did not improve the cure rate or shorten the
healing time in patients with Achilles tendinopathy6. Intratendinous injection of
corticosteroid can adversely affect tendon integrity and decrease the amount
of load that can be taken before failure16. Although intratendinous injection of
steroid is discouraged, Read found that the treatment group with peritendinous
injection of hydrocortisone in his cohort (n=64) with Achilles tendinopathy did
not have a higher rupture rate than the control group14.
Blind peritendinous injections without the use of imaging guidance may
inadvertently be delivered intratendinously. A randomized placebo-controlled
double blind study in patients with Achilles and patellar tendinopathy,
using ultrasound for the diagnosis and guided peritendinous injection of
triamcinolone, found that the treatment group had reduced pain and tendon
thickness9. Ultrasound (US) guided injection of a sclerosing agent polidocanol,
to the neovessels1,8,13 in 10 patients with Achilles tendinopathy showed reduced
pain in 8 patients with a corresponding reduction in neovascularity on colour
Doppler.
There have been attempts to treat Achilles tendinopathy through US guided
intralesional injections of 25% hyperosmolar dextrose solutions11. These studies
too have shown positive results, with reduction of tendinopathic areas in 78% of
the cases and reduction of the vascularization in 55% of the subjects.
More recently, there have been studies conducted in vitro and in vivo on tissue
regeneration at the site of tendon tears applying near the lesion an autologous
tissue enriched with growth factors2,7,10,12,15. These treatments are likely to
be directed at tendon tears and their application to Achilles tendinopathy is
debatable.
The widespread acceptance of neovascularisation and neoneural ingrowth on
the ventral aspect of the Achilles tendon as a main factor in the causation of
pain in mid-Achilles tendinopathy has led to a general agreement that injection
treatments should be peritendinous and not intratendinous, and image guided.
In addition, injection treatments as the sole method for treatment of Achilles
tendinopathy is unlikely to be successful in the long-term, if patients are to return
to their previous activities. A novel technique has recently been described and
published, High Volume Image Guided Injection (HVIGI). HVIGI followed by a
strict rehabilitation programme has excellent short and medium term results3,4,5
although there are limitations to the study, mainly sample size.
High Volume Image Guided Injections
Theory
The aim of this procedure is to reduce or obliterate the neovascularisation seen
on power Doppler US in patients with proven mid-Achilles tendinopathy, using
a US guided peritendinous injection. The patient then follows a strict post-
24
injection eccentric rehabilitation programme.

The primary objective of using this technique is to reduce the pain and stiffness
suffered by patients with chronic Achilles tendinopathy and for the patient also
to return to “normal activity” in 2 weeks post-injection.
Patients
Patients are referred with a clinical diagnosis of mid-Achilles tendinopathy to a
multidisciplinary Sports and Exercise one-stop clinic. The diagnosis is confirmed
using US. The contralateral Achilles is always also scanned. The size, shape,
morphological features and the neovascularisation with a new grading system
(Grade 0-V) of both Achilles are documented.
Inclusion Criteria Exclusion Criteria
- Aged 18-60 years - Systemic disease e.g. diabetes mellitus

- Resistant AT - Previous tendon surgery / injections
- Active sports person - Symptoms associated with trauma
- Desire to return to full activity - Coexisting causes of lower leg pain e.g.
ankle sprain, sciatica
Table 1: Inclusion criteria for patients to enter the HVIGI studies3,4,5.
However, patients who do not fit the inclusion criteria for the HVIGI study group,
can still be treated if they have recalcitrant chronic Achilles tendinopathy. In
particular there is no age limit, a significant number of patients do not have
exercise-induced symptoms and many patients have co-existent pathology (e.g.
back pain), but still need treatment to alleviate their symptoms.
Patients should have had a minimum of 4 weeks of eccentric exercise with no
significant improvement or they are unable to perform the eccentric exercises.
Patients have their US in a sitting up position (figures 1,2) as opposed to the
conventional prone position. This has the advantage that the patient can see
the operator (and vice-versa), they can see the US monitor and it easy to explain
the abnormalities. Patients are shown in real-time, how forced dorsi-flexion
(eccentric exercises) affects neovascularisation, to re-enforce the value of the
eccentric rehabilitation programme.
25
Figure 1: New method for scanning the Achilles tendon.
Figure 2: Operator can see patient and patient can see the problem / screen.
Patients are then informed of their US findings and correlation is then made with
the clinical findings and any previous investigations (e.g. previous US, MRI).
HVIGI – Method
The patient has an US prior to the HVIGI to confirm the diagnosis and to grade
the neovascularisation. The procedure is explained in detail and a verbal consent
is obtained. Patients who qualify for the HVIGI study also have a written consent.
The patient lies down in a supine position with external rotation the hip and
ankle, with hip and knee flexion to 45 degrees and the ankle and foot held in a
neutral relaxed position.
26
Figure 3: The patient lies down in a supine position with external rotation the hip
and ankle, with hip and knee flexion to 90 degrees and the ankle and foot held in a
neutral relaxed position.
Using real-time US guidance and an aseptic technique, a 21G needle is inserted

via a medial approach at the level of the maximum anteroposterior measurement
(usually but not always the site of maximum neovascularisation and tenderness).
The needle is connected to a high pressure connecting tube and a 10ml syringe,
which contains 10mls of 0.5% bupivacaine hydrochloride (Marcaine) and 25mgs
of hydrocortisone acetate.
Figure 4: Equipment for the HVIGI.
27
The needle is advanced between the interface of Kager’s fat pad and the ventral
(anterior) surface of the Achilles, in effect touching the surface of the Achilles
(which is a very sensitive structure) and parallel to the paratenon.
The 10ml solution is injected and this is followed by a further injection of 40mls
of 0.9% sodium chloride solution (saline), drawn up as 4 x 10ml syringes.
At the end of the procedure images are taken and a post-injection power Doppler
US is performed to confirm absence of the neovascularisation.
Post-injection Eccentric Rehabilitation Programme (PIERP)

After the injection, the patient is given a booklet with clear instructions of the
eccentric rehabilitation programme and the operator goes through the booklet.
Careful explanation with step-by-step instructions, are given to the patient and
emphasis is made on the need to avoid concentric exercises.
The PIERP consists of :
- 3 days rest;
- 3 days of eccentrics only;
- 3 days of eccentrics and non-impact exercises (e.g. swimming, cycling);
- Continuing eccentrics and gently start returning to full impact, depending on
symptoms;
- Back to normal activities within 3 days;
- Continue eccentrics for life;
Patients return for a check US at 2 weeks and see referring clinician at 2-3 weeks
post-injection for follow-up and clinical review.
Results of HVIGI
Prospective study4
Variable Mean Range Standard Deviation
Patient Age (Yrs) 43.5 22-59 11.6

Male: Female Ratio 7M:4F - -
Achilles Tendon Treated 6L:5R - -
Body Mass Index (kg/m2) 25.8 20.6-30.5 2.95
Duration of Symptoms (Mo.) 51.4 4-144 55.56
Duration Eccentrics (Mo.) 11.8 8-16 2.6
Table 2: Patient characteristics at baseline.
28
Sporting Activity Week Level of Sport Duration of Activity / (mins)
Running n=4 International (Professional) n=1 Mean 236.8

Gym Training n=2 National (Professional) n=1 Range 45-720
Badminton n=2 Club Level n=2 Standard Deviation 223.6
Walking n=1 Recreational / Fitness n=7
Pole Vault n=1
Football n=1
Table 3: Basic data on the sporting activities of the 11 patients with resistant non-
insertional Achilles tendinopathy prior to their symptoms.
Neovascularisation Number of Tendons (% of N=11)

Grade Baseline 3 weeks
0 0 (0%) 4 (36.4%)
1 1 (9.1%) 3 (27.3%)
2 3 (27.3%) 2 (27.3%)
3 2 (18.2%) 1 (9.1%)
4 5 (44.5%) 0 (0%)
5 0 (0%) 0 (0%)
Table 4: Neovascularisation score at baseline and at 3 week follow-up after HVIGI.
96
95
94
90
89
85
84
83
VISA-A Score
80
68
61
59
53
52
47
46
41
37
6
Before HVIGI After HVIGI
Table 5: Box and whisker plot to show VISA-A scores at baseline and 3 weeks post-
HVIGI.
29
4
Neovascularisation Score
Table 6: Box and whisker plot to show neovascularisation grade at baseline and 3
weeks post-HVIGI.
12.3
11.6
10.9
10.5
10.1
Tendon Diameter (mm)
9.9
9.8
8.9
8.6
8.3
8.1
8
7.9
7.5
6.8
6.5
6.2
5.7
5.5
5.3
4.5
Table 7: Box and whisker plot to show maximal tendon thickness (mm) at baseline
and 3 weeks post-HVIGI.
30
Follow-up Neovascularisation VISA-A Score Tendon Diameter

(mm) Grade
(Weeks)
Before After Before After Before After
3 3 2 53 80 10.9 10.5
3 1 0 6 62 5.7 5.5
3 2 0 46 96 7.5 6.5
3 4 1 47 68 6.2 5.3
3 2 1 59 85 8.9 7.9
3 3 0 37 95 6.5 4.5
3 4 1 41 94 9.8 8.1
2 2 0 52 90 8.0 6.8
2 4 2 68 84 12.3 11.6
4 4 2 47 89 10.1 8.3
3 4 3 53 83 9.9 8.6
Table 8: Data for outcome measures at baseline and follow-up in patient’s treated
with HVIGI for resistant non-insertional Achilles tendinopathy.
Sex Age when Hours of Sport Sport Level Returned Percentage Length of Length of
Injected Per Week Pre-injury to Sport? Improvment sporting Symptoms
(years) Pre-injury due to limitation (months)
injection (months)
M 29 5-10 Professional Yes - Same level 100 8 10

M 30 > 20 Professional Yes - Same level 82 0 19
M 27 > 20 Professional Yes - Same level 77 0 18
M 30 16-20 Professional No - Unable to 0 8 8
M 44 <5 County Yes - Same level 100 72 72
M 42 11-15 County Yes - Reduced level 79 276 276
M 24 16-20 Club Yes - Reduced level 66 2 2
M 47 <5 Club No - Haven't Tried 55 5 18
M 40 <5 Club Yes - Reduced level 51 24 29
M 42 11-15 Club Yes - Same level 0 6 18
F 33 5-10 Recreational Yes - Reduced level 96 4 4
F 44 <5 Recreational Yes - Same level 85 30 30
F 42 <5 Recreational Yes - Reduced level 80 18 24
M 34 5-10 Recreational Yes - Reduced level 74 3 3
M 34 11-15 Recreational Yes - Reduced level 26 8 10
M 41 5-10 Recreational Yes - Same level 100 0 60
M 58 > 20 Other Yes - Same level 100 120 120
Table 9: Patient data and questionnaire feedback regarding activity levels and
treatment.
31
Table 10: Mean retrospective VISA-A and VAS pain and function scores pre- and
post- HVIGI. VISA-A follow-up was performed long-term3,5.
Table 11: VISA-A score of each patient before and after HVIGI treatment. Lines of
best fit highlight the trends for the VISA-A scores.
Summary of retrospective3,5 and prospective4 studies of HVIGI
The studies confirm that HVIGI of recalcitrant chronic Achilles tendinopathy

significantly reduces the pain and symptoms, and improves short and long-term
function regardless of the level of symptoms, reduces the size of the tendon and
there is a reduction in the grade of neovascularisation.
HVIGI is a safe, simple, fast and efficient treatment for chronic Achilles
tendinopathy. The main advantage of this technique over all others, is that
patients are able to return to their “normal activities/sport” within 2 weeks of the
procedure.
30
Summary
Mid-tendon Achilles tendinopathy is generally considered to represent an

overuse injury with numerous intrinsic and extrinsic aetiological factors which
predispose an individual to developing symptoms. Recent evidence suggests
that the main aetiological factor for pain are neovascular and neoneural ingrowth
into the ventral aspect of the Achilles. This is supported by numerous studies
showing that treatments that obliterate or reduce the neovascularisation seen
on US Doppler, also reduce pain and stiffness and improve function.
Non-invasive treatments, in particular eccentric exercises should remain the
mainstay of initial treatment, but recalcitrant chronic Achilles tendinopathy
on theoretical grounds would be best treated with peritendinous rather than
intratendinous injections rather than surgery initially.
Numerous treatment options are available, but image guided US injections are
preferable to “blind” injections. The choice of which agent to inject is limited at
present and can be broadly divided into those that contain corticosteroids and
other substances.
HVIGI is a novel, fast cheap and very safe procedure that has excellent results,
both short and long-term. The main advantage of HVIGI over all the other
treatments is the return to “normal” activity within weeks rather than months, in
particular when dealing with elite or professional athletes.
References
2. BP Chan, SC Fu, L Qin, C Rolf, KM Chan. Supplementation-time dependence of growth factors in
promoting tendon healing. Clin Orthop Relat Res 2006;448:240-247.
3. Chan O, O’Dowd D, Padhiar N, Morrissey D, King L, Jalan R, Maffulli N, Crisp T. High volume image
guided injections in chronic Achilles tendinopathy. Disabil Rehabil. 2008;19:1-12.
4. Chan et al The short-term effects of High Volume image guided injections in Resistant Non-
Insertional Achilles Tendinopathy (in press) – unpublished data.
5. Crisp et al abstract. Br J Sports Med High volume image guided injections in chronic Achilles
tendinopathy. Br J Sports Med. 2007;41:122.
6. DaCruz DJ, Geeson M, Allen MJ, et al. Achilles paratendonitis: an evaluation of steroid injection. Br
J Sports Med 1988;22: 64-65.
7. LA Dahlgren, HO Mohammed, AJ Nixon. Temporal expression of growth factors and matrix
molecules in healing tendon lesions. J Orthop Res 2005;23:84-92.
8. R Depaoli, A Mayer, S Cattaneo, G Robotti. Terapia sclerosante sotto controllo color e power Doppler
nelle tendinopatie inserzionali. Giornale Italiano di Ecografia 2005;8:59-62.
9. Fredberg U, Pfeiffer-Jensen M, Stengaard Pederson K. Ultrasonography as a tool for diagnosis,
guidance of local steroid injection, and together with pressure algometry, monitoring of the
treatment of athletes with jumper’s knee and chronic Achilles tendonitis: a randomized, doubleblind,
placebo-controlled study. Scand J Rheumatol 2004;33:94-101.
10. Y Kajikawa, T Morihara, H Sakamoto, KI Matsuda, Y Oshima, A Yoshida, M Nagae, Y Arai, M Kawata,
T Kubo. Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon
healing. J Cell Physiol. 2008;215:837-45.
11. NJ Maxwell, MB Ryan, JE Taunton, JH Gillies, AD Wong. Sonographically guided intratendinous
injection of hyperosmolar dextrose to treat chronic tendinosis of the Achilles tendon: a pilot study.
AJR Am J Roentgenol 2007;189:215-220.
31
12. T Molloy, Y Wang, G Murrell. The roles of growth factors in tendon and ligament healing. Sports
Med 2003;33:381-394.
13. Ohberg L, Alfredson H. Ultrasound guided sclerosis of neovessels in painful chronic Achilles
tendinosis: pilot study of a new treatment. Br J Sports Med 2002;36:173-5.
14. Read MT. Safe relief of rest pain that eases with activity in Achillodynia by intrabursal or
peritendinous injection: the rupture rate was not increased by these steroid injections. Br J Sports
Med 1999;33:134-139.
15. LV Schnabel, HO Mohammed, BJ Miller, WG McDermott, MS Jacobson, KS Santangelo, LA
Fortier. Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum
superficialis tendons J Orthop Res 2007;25:230-240.
16. Speed CA. Corticosteroid injections in tendon lesions. BMJ 2001;323:382-386.
17. Tatari H, Kosay C, Ulukus C. Effect of heparin on tendon degeneration: an experimental study on
rats. Knee Surg Sports Traumatol Arthrosc 2001;9:247-253.
16
Autologous Blood Injections: Whole Blood and Platelet-Rich Plasma
“The blood is the life!”
(Bram Stoker, Dracula)
Chapter 13.
Autologous Blood
Injections: Whole Blood
and Platelet-Rich Plasma
Rebecca J. Kampa, David A. Connell
Take Home Message
• A pool of growth factors occur naturally within blood and these can be used to
stimulate the normal healing cascade
• Repair of the damaged tendon involves the recruitment of cells to lay down col
lagen which needs to become organised and typically takes up to 3 months.
• Physical therapy is necessary to augment the healing process
• Cell therapy offers further promise for the future.
Introduction
Tendinopathy in the Achilles tendon is often multifactorial with contributing

factors including genetic, biomechanical and regenerative faults. Excessive
loading during repetitive exercise is thought to be the main pathological
stimulus for intrasubstance degeneration and microtear formation. Continued
loading may lead to further evolution of these tears with intrasubstance splits,
macroscopic partial tears and even rupture. The latter may occur regardless of
any intervention.
17
There is no consensus on the treatment of Achilles tendinopathy. There have

been various treatments of tendinopathy described in the literature dating
back to the nineteenth century, including rest, non-steroidal anti-inflammatory
medication, bracing, physical therapy, steroid injection, dry needling and saline
injections. More recently, whole blood and platelet-rich plasma injections have
been increasingly used in clinical practice.
Basic Science
Normal tendon repair and regeneration involves 3 overlapping stages13,19,25.

The acute inflammatory stage is characterised by haematoma formation,
migration of blood cells into the injury site, phagocytosis of necrotic material,
release of pro-inflammatory cytokines and angiogenic factors, and fibroblast
(e.g. tenocytes) recruitment. After a few days the proliferative stage begins
with the continued recruitment and proliferation of fibroblasts, which are
primarily responsible for collagen (largely type 3) and proteoglycan synthesis,
as well as other components of the tendon extracellular matrix. During the final
remodelling stage approximately 6 weeks post injury, type 3 collagen decreases,
with an increase in type 1 collagen and its mechanical reorganisation (to run in
longitudinal bundles), as well as reduced glycosaminoglycan synthesis. During
consolidation (for up to 10 weeks), repair tissue changes to more fibrous tissue,
then gradually changing into scar-like tendon tissue whilst maturating over
the course of a year5. Normal physiological use of the tendon further induces
remodelling and acquisition of final tendon stability and strength.
Blood injections have been used in humans since the 1970’s. Healing of bone
and soft tissues is felt to be stimulated by growth factors and secretory proteins
that occur naturally within a patient’s own blood. It is proposed that these
growth factors recruit cells into tendon injury sites and then encourage them to
differentiate and proliferate into tenocytes so that they can lay down a collagen
network for tendon regeneration. (Figure 1).
However, whilst there are many basic science articles, animal studies and case
reports promoting these techniques, there are no good randomised clinical
studies providing strong clinical evidence.
16
Figure 1: Concept of Blood Injection therapy.
Research assessing the response of tendons to autologous blood injection has

been performed in rabbits23. This showed no difference in histology at 6 or 12
weeks or change in tendon stiffness when compared with normal tendon. The
tendon strength however had increased in the autologous blood group at 12
weeks.
Virchenko et al.24 showed stimulatory effects (increase force at failure, energy and
ultimate stress) on tendon repair at 14 days following Achilles tendon transection
in rats and platelet concentrate application with active or neutralised thrombin.
A further study in rats4 also showed improved tendon callus strength (force at
failure) and stiffness by up to a third after application of platelet concentrate to
the tendon gap. Histologically greater maturation of the tendon callus was noted
at 21 days. In sheep, Achilles tendons infiltrated with autologous fibrin matrices,
the presence of platelets significantly increased the proliferation of tendon cells2.
17
Whole Blood
The first case series reporting the use of autologous blood injections for the
treatment of tendinopathy was reported by Edwards et al, in which 22/28
patients with lateral epicondylitis demonstrated a marked reduction in pain and
functional score over a period of 9 months10. No adverse events or complications
were reported. Since then this technique has been applied for the treatment of
other tendinopathies. This author has reported cases series of autologous blood
injections using ultrasound guidance for the treatment of lateral epicondylitis,
medial epicondylitis and patellar tendinosis7,12,22. Although commonly performed,
there are no studies as yet reporting the use of whole blood in Achilles tendinosis.
Reports of improvement in symptoms following autologous blood injection
typically takes upwards of three months. The procedure does not initially
allieviate pain, however the underpinning philosophy is that if the incomplete
tears and areas of tendinosis heal then the pain will be relieved.
However, the exact mechanism of action remains uncertain. Growth factors have
been cited as the responsible agents in the repair process, although it may be
the complement system (i.e. Factor 3a) or it is possible that blood products may
simply incite an inflammatory response that triggers the healing cascade and
the formation of scar tissue. It is not uncommon for patients to have an intense
ache in the tendon soon after the injection of autologous blood, and in the case
of the Achilles tendon can occasionally be disabling. Furthermore, the number
and timing of the injections, and the quantity of blood injected has not been
optimally determined.
Platelet-Rich Plasma (PRP)
Recently, platelet-rich injections of blood have attracted a lot of interest in

the media following treatment of high profile athletes. There are a number of
growth factors contained in the alpha granules of the platelets. The philosophy
of platelet-rich plasma is that by concentrating the numbers of platelets, there
will be more growth factor and cellular mediators to orchestrate the healing
response. Platelets contain a number of proteins, cytokines and other factors that
initate and regulate wound healing. PRP typically contains a 3 to 5 fold increase
in platelet numbers. The basic cytokines identified in platelets are listed in Table
1, although many hundreds have been identified.
16
Site of release Action
Transforming growth factor – • Many cells • Cellular proliferation

ß (TGF-ß1) • Cellular migration
• Cell-matrix interactions
• Collagen synthesis (type 1 and 3)
Basic fibroblast growth factor • Fibroblasts • Angiogenesis

(b-FGF) • Inflammatory cells • Cellular proliferation
• Cellular migration
• Cell-matrix interactions
Platelet derived growth • Platelets • Expression and interaction of other

factor (PDGF) growth factors
• Cellular proliferation
• Angiogenesis
• Collagen synthesis
Insulin like growth factor • Platelets • Cellular proliferation

type 1 (IGF-1) • Plasma • Cellular migration
• Liver • Collagen synthesis
• Extracellular matrix synthesis (e.g.
proteoglycans) and remodelling
Vascular endothelial growth • Platelets • Neovascularisation/angiogenesis

factor (VEGF) • Increases capillary permeability
• Establishment and maintenance of
epitenon and endotenon vasculature
Epidermal growth factor (EGF) • Platelets • Cellular proliferation

• Chemotaxis
Bone morphogenetic protein • Platelets • Increased collagen type 1 expression

12 (BMP-12)*
Cartilage-derived morphoge- • Chondrocytes • Collagen synthesis (tendon-like tissue)

netic protein (CDMP)*† • Bone and cartilage formation
* Member of transforming growth factor – ß superfamily

† Also known as BMP-13 (CDMP-2) and BMP-14 (CDMP-1)
Table 1: Summary of growth factors playing a role in tendinopathy.
17
However, how these growth factors and cytokines precisely work remains
unknown. Following injection of blood or platelet-rich plasma into a tendon,
70% of the stored growth factors are released within 10 minutes and almost all of
the growth factors dissipate within an hour14. Despite this, clinical improvement
may take upwards of 12 weeks. Furthermore, the best proliferation in vitro
has been induced by physiological platelet concentrations (i.e 2.5 times blood
concentration) and higher platelet concentrations have been shown to induce
negative effects11. There is no clinical evidence that patients injected with platelet-
rich plasma concentrates have better clinical outcomes than those injected with
whole blood alone.
Mishra et al reported the use of plasma rich platelets in the treatment of

refractory elbow tendinosis15. A blinded trial between plasma rich platelets (15
patients) and bupivicaine alone (5 patients) was performed with 60% of patients
in the plasma rich platelet group reporting marked improvement in pain after
eight weeks, 81% at 6 months and 93% at final follow-up (range 12-38 months).
However, by 8 weeks, 3 of the 5 patients in the control group had withdrawn
from the study to seek other treatments making comparison difficult. This study
has obvious flaws but is one of the few studies that has been performed in a
prospective manner.
A more recent study by De Vos and colleagues9 performed a double-blind,

placebo-controlled trial in 54 patients with midportion Achilles tendinopathy
and randomised into PRP (n=27) or isotonic saline (n=27) groups. Both cohorts
then underwent an eccentric loading regimen and were followed for 24 weeks. By
study end, the mean VISA-A score improved in the PRP group by 21.7 points and
in the placebo group by 20.5 points. There was no significant difference between
the two groups and the authors concluded that there were no improvement
in pain or function in the PRP group. However, as a part of the trial design, a
course of eccentric loading was not performed prior to injection therapy (which
probably would have excluded many participants) and a sodium bicarbonate
buffer was added to the PRP injectate to neutralise the pH and this may have
interfered with growth factor activity. Regardless, this is the best designed study
that has made its way into the literature to date, and does raise many questions
about the validity of PRP therapy.
Procedure
The patient is asked to lie prone on the examination couch so that the Achilles
tendon can be assessed. Sonography of the tendon is performed to evaluate the
thickness, intrasubstance tears, complete tears and neovascularity. The presence
of partial tears extending to the tendon surface or rupture is a contraindication.
Blood is drawn from the antecubital fossa of the patient, with larger quantities
required for platelet-rich plasma injection. This author typically takes off 3ml for a
whole blood injection and 10ml for a PRP injection. The latter is centrifuged and
the buffy coating found at the interface of the sedimented red cells and plasma
16
is extracted. An anticoagulant (i.e citrate) is typically added to bind ionised

calcium and inhibit the clotting cascade. An activating agent is not used (or felt
necessary).
The deep surface of the Achilles tendon is infiltrated using a 21G needle and a
bolus of 5 mls of local anaesthetic. After an interval of several minutes, the needle
is placed under ultrasound guidance into the site of maximal tendon injury (Fig
2a) and the blood is injected into the sites of tendinopathy and fibril discontinuity.
At the time of injection a number of intrasubstance tears and longitudinal splits
become prominent and readily visible where they were not seen readily seen
prior to injection (Fig 2b).
a b
Figure 2a: The needle is guided to the area of maximal tendon injury. The arrow rests
on the needle tip. Blood is injected as the needle is gradually withdrawn to the skin
surface.
Figure 2b: An intrasubstance tear which was not initially visible is seen to open up
above the original site of injection as the injection takes place (arrow).
Figure 3 Figure 4
Figure 3: 10 ml of blood has been centrifuged for 12 minutes to separate the blood
constituents. The buffy coating containing the concentrated platelets is aspirated
and injected (arrow).
Figure 4: Three months following PRP treatment. Remodelling and healing of the
tendon substance is noted with linear echogenic bands of scar tissue (arrow).
17
Rehabilitation and follow-up
Following injection the patient is advised to continue with normal activities

but no exercise. After three days, an eccentric loading calf muscle programme
is commenced1. The patient is asked to perform the exercises daily for the next
twelve weeks. These eccentric loading programmes are important in enabling the
organisation and alignment of scar tissue formation, in addition to maintaining
function of the tendon and calf musculature.
Follow up ultrasound at 6-8 weeks is usually performed. The tendon is assessed

with regards to thickness, appearance and tears. The thickness is often reduced
with echogenic scar tissue formation. Often there is partial resolution of tears
seen at initial presentation. Tendon vascularisation may decrease but can often
take up to a year before it completely resolves. The tendon may be injected a
second time depending on the response and continuing symptoms. Anecdotal
evidence suggests that there is a cumulative benefit to 2 or more injections.
Tips and tricks
A 5ml bolus of local anaesthetic can be used to strip away (paratenon stripping)
the loose connective tissue, neovessels and nerves surrounding the Achilles
tendon. This can make the blood injection painless and provide pain relief for
weeks afterwards. Allowing at least 5 minutes for the local anaesthetic to work
can make the procedure a lot more comfortable for the patient although the
injection is intratendinous and not entirely pain free.
Gentle injection of blood whilst withdrawing the needle from the deep tendon
surface will allow blood to dissipate into intrasubstance clefts and fissures.
Aggressive needling may result in further tearing and lead to rupture, although
it is recognised that this process in itself might stimulate healing.
Injecting the tendon in the longitudinal plane is easier to identify and fill the
intrasubstance tears which run in this plane. Transverse injections limit the
injectate coverage. Sometimes, with diffuse tendinosis, multiple injection points
are necessary.
Rupture
There is no role for autologous blood injections into acute Achilles tendon
ruptures, as any blood injected into a gap will simply dissipate. However, there
may be a role in the augmentation of Achilles tendon repair. Sanchez et al18.
performed a small study on augmentation of surgical Achilles tendon repair
with platelet rich fibrin matrix (6 patients), and retrospectively compared this
to patients who received a non-enhanced repair. No complications were noted
and the patients receiving the matrix with had significantly better range of
movement, earlier return to gentle running. Other researchers are also using
blood injections to augment surgical procedures16.
16
Regulation
The World Anti-Doping Agency (WADA) has recently approved the use of
autologous blood and platelet-rich plasma for the treatment of athletes.
However, limitations are still in place for the injection of platelet-rich plasma into
muscle injuries. The procedure has been recognised by the National Institute
for Health and Clinical Excellence (NICE) in the United Kingdom provided that
it is performed in accordance with clinical governance and under the remit of
continuing audit and review20.
Cell Therapy
Cell therapy is a particularly attractive option for tendinopathies as tendon in

its natural state has a relatively low resident cell population and tissue turnover
rate. Several experimental studies have shown a significant improvement in
healing of tendon lesions using bone marrow derived mesenchymal stem cells.
This approach has shown improved mechanical properties in rabbit Achilles
and patellar tendon and better aligned collagen fibres6 suggesting a functional
tendon-like matrix is produced. In clinical veterinary medicine, bone marrow
derived MSCs harvested from the sternum have been used to treat superficial
digital flexor tendonitis in horses and results look promising with many horses
returning to their former racing career3,21. However, although bone marrow
derived MSCs have been investigated in vitro and in animal models, clinical trials
in human patients for the treatment of tendinopathies have yet to be reported.
A recent pilot study has attempted to regenerate tendons by injecting collagen-

producing cells from skin fibroblasts, into the site of tendon injury8. Eleven of 12
patients with refractory lateral epicondylitis and marked improvement in pain
and function scores 3 months after an injection of cells and plasma into the site of
tendon injury. This offers the benefit of using the growth factors found naturally
in blood to augment the regenerative process. No adverse events were reported.
Ultrasound confirmed features of regeneration with a tendency of intrasubstance
tears to heal and the tendon architecture to return towards normality.
In summary, cell therapy offers the promise of treating a range of tendon

disorders. It is likely to provide a better qualitative outcome through regeneration
of the injured tendon, rather than repair with scar tissue formation. Preliminary
results are encouraging but a lot more research needs to be done.
Conclusion
Achilles tendinopathy is a common source of disability and can be recalcitrant

to conservative measures. Blood, and in particular platelets, are a rich source of
factors necessary for tissue healing. Autologous blood injections are thought to
promote tendon healing, but have been explored clinically in only a few limited
17
studies. The mechanism of action remains unknown and there is no evidence that
platelet concentrates are any better than the injection of whole blood. However,
blood injections are safe, minimally invasive and an inexpensive procedure, and
blood can be simply acquired and prepared. At present, there is no hard evidence
that blood injections work, and hence long term well conducted studies of
sufficient sample size, using validated clinical, radiological and biomechanical
measure are needed.
References
1. Alfredson H. et al. Chronic Achilles tendinosis: recommendations for treatment and prevention.
Sports Med 2000;29:135-46.
2. Anitua E, Sanchez M, Nurden AT, et al. Autologous fibrin matrices: a potential source of biological
mediators that modulate tendon cell activities. J Biomed Mater Res A 2006;77:285-93.
3. Arguelles et al. Autologous platelet concentrates as a treatment for musculoskeletal lesions in five
horses. Vet Rec 2008;162:208-11.
4. Aspenberg P, Virchenko O. Platelet concentrate injection improves Achilles tendon repair in rats.
Acta Orthop Scand 2004;75:93-9.
5. Aspenberg P. Stimulation of tendon repair: mechanical loading, GDFs and platelets. A mini-review.
Int Orthop 2007;31:783-9
6. Awad, H.A. et al. (2003) J Orthop Res 21: 420-431.
7. Connell et al. Ultrasound-guided autologous blood injection for tennis elbow. Skeletal Radiol
2006;35:371-7.
8. Connell et al. Treatment of lateral epicondylitis using skin-derived tenocyte-like cells. Br J Sports
Med 2009;43:25-29.
9. De Vos R, Weir A, van Schie H, et al. Platelet-rich Plasma injection for chronic Achilles tendinopathy.
JAMA 2010;303:144-49.
10. Edwards et al. Autologous blood injections for refractory lateral epicondylitis. J Hand Surg
2003;28:272-8
11. Graziani F. et al. The in vitro effect of different PRP concentrations on osteoblasts and fibroblasts.
Clin. Oral Implants Res. 2006;17: 212-219.
12. James et al. Ultrasound guided dry needling and autologous blood injection for patellar
tendinosis. Br J Sports Med 2007;41: 518-21.
13. James R, Kesturu G, Balian G, et al. Tendon: biology, biomechanics, repair, growth factors, and
evolving treatment options. J Hand Surg 2008;33:102-12.
14. Marx RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 2001;10:225-
228.
15. Mishra et al. Treatment of Chronic Elbow Tendinosis With Buffered Platelet-Rich Plasma.
Am J Sports Med 2006;34:1774-1778.
16. Moon et al. Autologous bone marrow plasma injection after arthroscopic debridement for elbow
tendinosis. Ann Acad Med Singap 2008;37:559-63.
17. National Institute for Health and Clinical Excellence;Autologous blood injection for tendinopathy.
2009.
18. Sanchez et al. Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin
matrices. Am J Sports Med 2007;35:245-51.
19. Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg (Am)
2005;87:187-202.
20. Sharma P, Maffulli N. Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet
Neuronal Interact 2006;6:181-190.
21. Smith, R.K. et al. Equine Vet J 2003;35: 99-102.
22. Suresh et al. Medial epicondylitis: is ultrasound guided autologous blood injection an effective
treatment?. Br J Sports Med 2006;40:935-9.
23. Taylor et al. The response of rabbit patellar tendons after autologous blood injection. Medicine
and science in sports and exercise 2002;34:70-3.
24. Virchenko O, Grenegard M, Aspenberg P. Independent and additive stimulation of tendon repair
16
by thrombin and platelets. Acta Orthop 2006;77:960-6.

25. Xu Y, Murrell GA. The basic sciences of tendinopathy. Clin Orthop Relat res. 2008;466:1528-38.
17
16
Minimally Invasive Surgery for Achilles Tendinopathy
“Through small steps you can reach the top”
(N. Maffulli)
Chapter 14.
Minimally Invasive
Surgery for Achilles
Tendinopathy
Nicola Maffulli, Umile Giuseppe Longo, Vincenzo Denaro
Take Home Message
1. Minimally invasive surgery for patients with tendinopathy of the main body
of the Achilles tendon include multiple percutaneous longitudinal tenotomies,
eventually ultrasound-guided, minimally invasive stripping and tendoscopy
2. Proposed advantages of minimally invasive surgery include shorter hospital
stays, faster recovery times, decreased chance of wound breakdown and infec-
tion, reduced iatrogenic disruption of the subcutaneous tissues and paratenon,
and improved functional outcomes. Sural nerve damage remains the most im-
portant concern.
3. Several different minimally invasive modalities address the area of neo-vas-
cularisation and neo-innervation around the tendon, including stripping of the
tendon
Introduction
Minimally invasive is gaining increased worldwide interest in all the fields of

trauma and orthopaedic surgery 5-8, 11-14, 17-23, 28, 30, 32, 33. Arthroscopy has been the
major development that has probably influenced the management of sports
medicine injuries more than any other procedure, becoming a necessary tool
17
for the management of many intra-articular pathologies. Theoretical advantages

of minimally invasive procedures include decreased recovery and rehabilitation
times, because of gentler surgical exposure and less extensive deep soft tissue
dissection. Minimally invasive procedures may reduce surgical trauma because
they are performed with small incisions, and injury to the soft tissues is limited.
These techniques hold the promise to provide better clinical outcome for patients
who would not recover well from traditional open approaches 30, 34.
Achilles tendinopathy is common, and is associated with considerable health
expenses. To simplify surgery and minimize complications, minimally invasive
techniques have been proposed, including tendoscopy, percutaneous and
minimum incision surgery. The proposed benefits of minimally invasive surgery
for Achilles tendon pathologies over traditional open techniques include shorter
hospital stays, faster recovery times, decreased chance of wound breakdown
and infection, reduced iatrogenic disruption of the subcutaneous tissues and
paratenon, and improved functional outcomes 2, 3, 14, 21, 25. Sural nerve damage
remains the most important concern 15, 16.
Arthroscopic procedures have demonstrated decreased morbidity in a variety of
joints. The advantages of a standard arthroscopic procedure are well documented
in the literature: smaller and more cosmetically appealing incisions, less surgical
dissection, less perioperative pain experienced by the patient, and a procedure
that can be performed as an outpatient. Different endoscopic techniques have
been described for the management of Achilles tendinopathy 36, 39.
Percutaneous and minimum incision surgery for the management of patients
with Achilles tendinopathy have received increasing recognition because of
the perceived efficacy comparable to traditional open approaches but with
purported less cost and higher patient satisfaction. Percutaneous surgery is
performed through the smallest possible working incision (usually 1 to 3 mm
long) without direct visualization of the underlying target structures. Minimally
incision surgery is performed through the smallest incision necessary to perform
the procedure (usually 1 to 3 cm long).
We report our experience in minimally invasive surgery for the management
of patients with tendinopathy of the main body of the Achilles tendon 14, 18, 19,
21, 25
, including multiple percutaneous longitudinal tenotomies 25, 38 (eventually
ultrasound-guided 37), and minimally invasive stripping 14. Endoscopy 36, 39 will be
discussed in another chapter of this book.
Multiple percutaneous longitudinal tenotomies
Surgical technique
The patient is positioned prone with the feet protruding from the edge of the
operating table. The ankles rest on a padded sandbag 25. The Achilles tendon is
palpated, and the area of maximum swelling and/or tenderness is marked and
checked again by ultrasound scanning. The skin and the subcutaneous tissues
over the Achilles tendon are infiltrated with 10 to 15 mL of plain 1% lignocaine
(Lignocaine Hydrochloride, Evans Medical Ltd, Leatherhead, England). A number
11 surgical scalpel blade is inserted parallel to the long axis of the tendon fibers in
16
the marked area(s) with the cutting edge pointing cranially. This initial stab incision
is produced in the central portion of the tendinopathy lesion. With the blade
still, a full passive ankle dorsiflexion movement is produced. The position of the
blade is reversed, and a full passive ankle plantarflexion movement is produced.
A longitudinal tenotomy is thereby achieved over an area of approximately 3 cm
using only a stab incision. The procedure is repeated 2 cm medial and proximally,
medial and distally, lateral and proximally, and lateral and distally to the site of
the first stab wound. The pattern of the 5 stab incisions is similar to the number
5 on a dice. The 5 wounds are closed with steristrips, dressed with cotton swabs,
and several layers of cotton wool and a crepe bandage are applied. The same
procedure can be performed under ultrasound guidance.
Minimally invasive stripping

Classically, open surgery for the management of tendinopathy of the main body
of the AT aimed to treat the area of tendinopathy inside the tendon to remove
degenerated nodules, excise fibrotic adhesions and, eventually, to perform
multiple longitudinal incisions in the tendon 31.
It has been proposed that neo-vascularisation and neo-innervation may be
responsible for developing Achilles tendinopathy1, 9, 10, 13, 24, 26, 27, 29. Moreover,
patients perceive most pain in the area where most neo-vascularisation is
detected on power Doppler ultrasound scan 29. Several different management
modalities have been developed to address the area of neo-vascularisation and
neo-innervation around the tendon 4, 14, 36, 39, 40.
Surgical technique
The procedure can be performed under local or general anaesthesia, according
to surgeon or patient preferences 14, 18, 21. The patient is positioned prone with
a calf tourniquet which is inflated to 250 mmHg after exsanguination. Skin
preparation is performed in the usual fashion.
Four skin incisions are made. Two 0.5 cm longitudinal incisions are made at the
proximal origin of the Achilles tendon, just medial and lateral to the origin of the
tendon. The other two incisions are located 1 cm distal to the distal end of the
tendon insertion on the calcaneus.
A mosquito is inserted in the proximal incisions, and the Achilles tendon is freed
of the peritendinous adhesions. A Number 1 unmounted Ethibond (Ethicon,
Somerville, NJ) suture thread is passed through the two proximal incision
(Figure 1). The Ethibond is retrieved from the distal incisions (Figure 2), over the
posterior aspect of the Achilles tendon. Using a gentle see-saw motion (Figure 3),
the Ethibond suture thread slides anterior to the tendon, which is stripped and
freed from the fat of Kager’s triangle. If necessary, using an 11 blade, longitudinal
percutaneous tenotomies parallel to the tendon fibres are made25, 35, 37.
The skin is closed in a routine fashion (Figure 4). A removable scotch cast support
with Velcro straps can be applied if deemed necessary.
17
Figure 1: Minimally invasive stripping of neovessels from the anterior aspect of the
tendinopathic Achilles tendon. A mosquito is inserted in the proximal incisions.
Figure 2: The Ethibond is retrieved from the distal incisions.
16
Figure 3: The Ethibond is slid over the anterior aspect of the Achilles tendon with a
gentle see-saw motion.
Figure 4: The final results.
Conclusions
Minimally invasive surgery for the management of patients with tendinopathy of

the main body of the AT is rapidly developing. It is ideal for patients with increased
risks of wound complications as it reduce the morbidity associated with extensile
incisions. Given the limitations of the case series on the topic, it is not possible
to determine clear recommendations regarding the systematic use of minimally
invasive surgery for every patient. In our hands, minimally invasive surgery
has provided similar results to those obtained with open surgery, providing
decreased duration of hospital stay, decreased perioperative morbidity, and
reduced costs. These procedures do not require highly specialized equipment and
training and are inexpensive. In many cases, it must be remembered minimally
invasive open approach has not rendered open surgery obsolete. Rather, it is
another tool in the surgeon’s armamentarium and it, like any other tool, must
17
be used appropriately to ensure the patient the best possible outcome with the
least chance for complications. Clearly, studies of higher levels of evidence, for
instance large randomised trials, should be conducted to help answer these
questions. Future trials should use validated functional and clinical outcomes,
adequate methodology, and be sufficiently powered.
References
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2. Carmont MR, Maffulli N. Less invasive Achilles tendon reconstruction. BMC Musculoskelet Disord.
2007;8:100.
3. Carmont MR, Maffulli N. Modified percutaneous repair of ruptured Achilles tendon. Knee Surg
4. Chan O, O’Dowd D, Padhiar N, Morrissey D, King J, Jalan R, Maffulli N, Crisp T. High volume image
guided injections in chronic Achilles tendinopathy. Disability and rehabilitation. 2008;30:1697-1708.
5. Denaro L, Longo UG, Denaro V. Vertebroplasty and kyphoplasty: reasons for concern? The
Orthopedic clinics of North America. 2009;40:465-471.
6. Gougoulias N, Khanna A, McBride DJ, Maffulli N. Management of calcaneal fractures: systematic
review of randomized trials. British medical bulletin. 2009;92:153-167.
7. Ho M, Garau G, Walley G, Oliva F, Panni AS, Longo UG, Maffulli N. Minimally invasive dynamic hip
screw for fixation of hip fractures. Int Orthop. 2009;33:555-560.
8. Khanna A, Gougoulias N, Longo UG, Maffulli N. Minimally invasive total knee arthroplasty: a
systematic review. Orthop Clin North Am. 2009;40:479-489.
9. Knobloch K, Kraemer R, Lichtenberg A, Jagodzinski M, Gossling T, Richter M, Zeichen J, Hufner
T, Krettek C. Achilles tendon and paratendon microcirculation in midportion and insertional
tendinopathy in athletes. Am J Sports Med. 2006;34:92-97.
10. Kristoffersen M, Ohberg L, Johnston C, Alfredson H. Neovascularisation in chronic tendon injuries
detected with colour Doppler ultrasound in horse and man: implications for research and treatment.
Knee Surg Sports Traumatol Arthrosc. 2005;13:505-508.
11. Longo UG, Denaro V. Spinal augmentation: what have we learnt? Lancet. 2009;373:1947
12. Longo UG, Maffulli N, Denaro V. Minimally invasive total knee arthroplasty. N Engl J Med.
2009;361:633-634
13. Longo UG, Papapietro N, Maffulli N, Denaro V. Thoracoscopy for minimally invasive thoracic spine
surgery. Orthop Clin North Am. 2009;40:459-464.
14. Longo UG, Ramamurthy C, Denaro V, Maffulli N. Minimally invasive stripping for chronic Achilles
tendinopathy. Disabil Rehabil. 2008;30:1709-1713.
15. Longo UG, Ronga M, Maffulli N. Achilles tendinopathy. Sports Med Arthrosc. 2009;17:112-126.
16. Longo UG, Ronga M, Maffulli N. Acute ruptures of the achilles tendon. Sports Med Arthrosc.
2009;17:127-138.
17. Maffulli N, Longo UG, Denaro V. Complications after surgery or nonoperative treatment for acute
achilles tendon rupture. Clin J Sport Med. 2009;19:441-442.
18. Maffulli N, Longo UG, Denaro V. Letter to the editor: Minimally invasive paratenon release for non-
insertional Achilles tendinopathy. Foot Ankle Int. 2009;30:1027-1028.
19. Maffulli N, Longo UG, Gougoulias N, Denaro V. Ipsilateral free semitendinosus tendon graft transfer
for reconstruction of chronic tears of the Achilles tendon. BMC Musculoskelet Disord. 2008;9:100.
20. Maffulli N, Longo UG, Oliva F, Denaro V, Coppola C. Bosch osteotomy and scarf osteotomy for
hallux valgus correction. Orthop Clin North Am. 2009;40:515-524.
21. Maffulli N, Longo UG, Oliva F, Ronga M, Denaro V. Minimally invasive surgery of the achilles
tendon. Orthop Clin North Am. 2009;40:491-498.
22. Maffulli N, Longo UG, Ronga M, Khanna A, Denaro V. Favorable Outcome of Percutaneous Repair
of Achilles Tendon Ruptures in the Elderly. Clin Orthop Relat Res. 2010;468:1039-1046.
23. Maffulli N, Longo UG, Spiezia F, Denaro V. Free hamstrings tendon transfer and interference screw
fixation for less invasive reconstruction of chronic avulsions of the Achilles tendon. Knee Surg Sports
16
Traumatol Arthrosc. 2010;18:269-273.

24. Maffulli N, Sharma P, Luscombe KL. Achilles tendinopathy: aetiology and management. J R Soc
Med. 2004;97:472-476.
25. Maffulli N, Testa V, Capasso G, Bifulco G, Binfield PM. Results of percutaneous longitudinal tenotomy
for Achilles tendinopathy in middle- and long-distance runners. Am J Sports Med. 1997;25:835-840.
26. Maffulli N, Testa V, Capasso G, Ewen SW, Sullo A, Benazzo F, King JB. Similar histopathological
picture in males with Achilles and patellar tendinopathy. Med Sci Sports Exerc. 2004;36:1470-1475.
27. Maffulli N, Wong J, Almekinders LC. Types and epidemiology of tendinopathy. Clin Sports Med.
2003;22:675-692.
28. Mahmood A, Zafar MS, Majid I, Maffulli N, Thompson J. Minimally invasive hip arthroplasty: a
quantitative review of the literature. British Medical Bulletin. 2007;84:37-48.
but not in normal tendons: an ultrasonographic investigation. Knee Surg Sports Traumatol Arthrosc.
2001;9:233-238.
30. Oliva F, Longo UG, Maffulli N. Minimally invasive hallux valgus correction. Orthop Clin North Am.
2009;40:525-530
31. Rolf C, Movin T. Etiology, histopathology, and outcome of surgery in achillodynia. Foot Ankle Int.
1997;18:565-569.
32. Ronga M, Longo UG, Maffulli N. Minimally Invasive Locked Plating of Distal Tibia Fractures is Safe
and Effective. Clin Orthop Relat Res. 2010;468:975-982.
33. Ronga M, Shanmugam C, Longo UG, Oliva F, Maffulli N. Minimally invasive osteosynthesis of distal
tibial fractures using locking plates. Orthop Clin North Am. 2009;40:499-504.
34. Roukis TS. Percutaneous and minimum incision metatarsal osteotomies: a systematic review. J
Foot Ankle Surg. 2009;48:380-387.
tendinopathy. J Sci Med Sport. 2007;10:52-58.
36. Steenstra F, van Dijk CN. Achilles tendoscopy. Foot Ankle Clin. 2006;11:429-438.
37. Testa V, Capasso G, Benazzo F, Maffulli N. Management of Achilles tendinopathy by ultrasound-
guided percutaneous tenotomy. Med Sci Sports Exerc. 2002;34:573-580.
38. Testa V, Maffulli N, Capasso G, Bifulco G. Percutaneous longitudinal tenotomy in chronic Achilles
tendonitis. Bull Hosp Jt Dis. 1996;54:241-244.
39. Thermann H, Benetos IS, Panelli C, Gavriilidis I, Feil S. Endoscopic treatment of chronic mid-portion
Achilles tendinopathy: novel technique with short-term results. Knee Surg Sports Traumatol Arthrosc.
2009;17:1264-1269.
40. Willberg L, Sunding K, Öhberg L, Forssblad M, Fahlström M, Alfredson H. Sclerosing injections
to treat midportion Achilles tendinosis: a randomised controlled study evaluating two different
concentrations of Polidocanol. Knee Surg Sports Traumatol Arthrosc. 2008;16:859-864.
17
16
Achilles Tendoscopy
“Scopaholicism confirmed”
(M.N. van Sterkenburg)
Chapter 15.
Achilles Tendoscopy
Maayke N. van Sterkenburg, Hajo Thermann, C. Niek van Dijk
Take Home Message
• It is questionable whether degeneration of the tendon proper causes complaints.

• Endoscopic release of the peritendineum renders good results in the treatment.
of paratendinopathy and a combination of Achilles tendinopathy and
paratendinopathy.
Introduction
If conservative measures fail, surgery must be considered. The percentage of

patients requiring surgery is around 25%7-9. The technique used for operative
management of tendinopathy depends on the stage of the disease. Local
degeneration and thickening are usually treated by excision and curettage. An
insufficient Achilles tendon due to extensive degeneration can be reconstructed.
Isolated paratendinopathy can be treated by excision of the diseased
peritendineum.
Open surgery has a guarded prognosis, and is associated with a higher risk
of complications than endoscopic treatment1,4,11. Open techniques are also
associated with an extensive rehabilitation period of 4-12 months. Therefore,
recently minimally invasive techniques were developed.
17
In combined tendinopathy and paratendinopathy, the question is whether both

pathologies contribute to the complaints. An anatomic cadaver study described
degenerative changes of the Achilles tendon in as much as 34% of subjects with
no complaints5.
Khan and co-workers only found abnormal morphology in 65% (37 of 57) of
symptomatic tendons, but also in 32% (9 of 28) of asymptomatic Achilles tendons
assessed by ultrasound6. Therefore, it is questionable whether degeneration
of the tendon itself is the main cause of the pain. Neovascularisation and
accompanying sensory nerves from the ventral paratendinous tissue have been
described to possibly facilitate pain transmission in Achilles tendinopathy2,3.
‘Denervation’ of the Achilles tendon by releasing the peritendineum from the
Achilles tendon proper may therefore be sufficient to resolve complaints. In
this chapter 2 endoscopic approaches for treating Achilles tendinopathy are
described.
Surgical technique
The first surgical technique focuses on management of the paratendinopathy

only; leaving the nodular thickened tendon proper untouched even when an
intratendinous lesion is present.
Local, epidural, spinal and general anaesthesia can be used for this procedure,
which can be performed on an outpatient basis. The patient is in the prone
position. A tourniquet is placed around the thigh of the affected leg, and a
bolster is placed under the foot. Because the surgeon needs to be able to obtain
full plantar and dorsiflexion, the foot is placed right over the end of the table.
A 2.7 mm arthroscope for endoscopy of a combined tendinopathy and
paratendinopathy is mostly used. This small- diameter short arthroscope yields
an excellent picture comparable to the standard 4 mm arthroscope; however, it
cannot deliver the same amount of irrigation fluid per time as the 4 mm sheath.
Therefore a pressurized bag or pump device sometimes is used with the 2.7 mm
arthroscope.
The distal portal is located on the lateral border of the Achilles tendon, 2-3 cm
distal to the pathologic nodule. The proximal portal is located medial to the
border of the Achilles tendon, 2-4 cm above the nodule. When the portals are
placed this way, it is usually possible to visualize and work around the complete
surface of the tendon, over a length of approximately 10 cm.
The distal portal is made first. After making the skin incision, the mosquito
clamp is introduced, followed by the blunt 2.7 mm trocar in a craniomedial
direction. With this blunt trocar the peritendineum is approached, and is blindly
released from the tendon by moving around it (Figure 1A). Subsequently,
the 2.7 mm 30° arthroscope is introduced. To minimize the risk of iatrogenic
damage, the arthroscope should be kept on the tendon. At this moment, it can
be confirmed whether the surgeon is in the right layer between the deepest
layer of the paratenon and Achilles tendon (Figure 1B). If not, it can now be
identified and a further release can be performed.
16
Achilles Tendoscopy
Figure 1: A) Blind release of the peritendineum from the Achilles tendon. B) Endo-
scopic view: releasing the peritendineum from the Achilles tendon.
The proximal portal is made by introducing a spinal needle, followed by a mosquito

clamp and probe. The plantaris tendon can be identified at the anteromedial
border of the Achilles tendon. In a typical case of local paratendinopathy, the
plantaris tendon, the Achilles tendon, and the peritendineum are tight together in
the process. Removal of the local thickened peritendineum on the anteromedial
side of the Achilles tendon at the level of the nodule, and release of the plantaris
tendon are the goals of this procedure. In cases where the fibrotic peritendineum
is firmly attached to the tendon, a release is performed. Neovessels can be found
and are removed with a 2.7 mm full radius resector. Changing portals can be
helpful. At the end of the procedure it must be possible to move the arthroscope
over the complete symptomatic area of the Achilles tendon. After the procedure,
the portals are sutured.
Aftercare consists of a compressive dressing for 2-3 days. Patients are encouraged
to actively perform range of motion exercises. Full weight-bearing is allowed as
tolerated. Initially, the foot must be elevated when not walking.
An alternative technique was published in 200913. This approach focuses on the

paratendinopathy as well as the tendinopathy. Positioning is similar. Two portals
are created medially from the Achilles tendon. The proximal portal is placed 10-
12 cm proximal to the posterior calcaneal tuberosity, near the tendon-muscle
junction. This portal is used to introduce a 4.5 mm arthroscope. The distal portal
is created just above the calcaneal tuberosity for the introduction of a 4.5 mm
full radius resector and for other instruments. As in the technique described
above, the peritendineum is released from around the Achilles tendon. Special
attention is given to the ventral side of the tendon, where neovascularisation
and accompanying sensory nerves may facilitate pain transmission in Achilles
tendinopathy2,3. Additionally, in case of a combined peritendinopathy and
tendinopathy of the tendon proper, two parallel longitudinal incisions according
to the site of the lesion on MRI are made in the Achilles tendon using a retrograde
knife blade (Figure 2).
Aftercare is similar to the first technique, except for that full weight-bearing is
allowed after the removal of stitches on the 14th postoperative day.
17
Figure 2: Longitudinal tenotomy under direct vision.
Results
Steenstra and Van Dijk earlier described the results of 20 patients treated by
means of release of the paratendinopathy only12. All patients had a combination
of paratendinopathy and tendinopathy and had complaints for more than 2 years.
They had undergone a period of at least 6 months of conservative treatment
before the indication for surgery was set. The results were analyzed with a follow
up of 2-7 years with a mean of 6 years. Sixteen patients were assessed at follow
up, which included completing of subjective outcome scores. The Foot and
Ankle Outcome Score (FAOS) and the Short Form general health survey with
36 questions (SF-36) were utilized. There were no complications. Most patients
were able to resume their sporting activities after 4 to 8 weeks. All patients had
significant pain relief. The results of the subjective outcome scores used were
comparable to a cohort of people without Achilles tendon complaints.
Maquirriain and co-workers reported the outcome of 7 patients who underwent
an endoscopic release for chronic Achilles tendinopathy, with similar results.
The mean score of this group improved from 39 pre-operatively to 89 post-
operatively (on a scale of 0-100), and there were no complications10. Vega and
co-workers published a modified endoscopic technique for the treatment of
Achilles tendinopathy in 200814. Pathological tissue was endoscopically removed,
and multiple longitudinal tenotomies were performed using a retrograde knife
blade. They reported a series of 8 patients with an excellent outcome, return to
their previous sports activities and no complications.
The results of the second technique described in this chapter were published in
200913. 8 patients were endoscopically treated, of which 5 received additional
longitudinal tenotomies. All 8 patients experienced immediate pain relief after
the procedure and at follow-up of at least 6 months, pain decreased from a mean
VAS of 36 pre-operatively to 95 post-operatively. All patients were satisfied with
the outcome.
16
Achilles Tendoscopy
Conclusion
The results of endoscopic surgery for Achilles tendinopathy seem promising.

More experience must be acquired by different orthopaedic surgeons. Also,
accurately designed studies need to be performed, to optimize the technique
and to ultimately be able to offer patients this minimally invasive treatment with
its great advantages
References
1. Abramowitz Y, Wollstein R, Barzilay Y et al. Outcome of resection of a symptomatic os trigonum. J

Bone Joint Surg Am 2003;85-A:1051-7.
3. Andersson G, Danielson P, Alfredson H, Forsgren S. Nerve-related characteristics of ventral
paratendinous tissue in chronic Achilles tendinosis. Knee Surg Sports Traumatol Arthrosc
2007;15:1272-9.
4. Hamilton WG, Geppert MJ, Thompson FM. Pain in the posterior aspect of the ankle in dancers.
Differential diagnosis and operative treatment. J Bone Joint Surg Am 1996;78:1491-1500.
6. Khan KM, Forster BB, Robinson J et al. Are ultrasound and magnetic resonance imaging of value in
assessment of Achilles tendon disorders? A two year prospective study. Br J Sports Med 2003;37:149-
53.
7. Kvist M. Achilles tendon injuries in athletes. Ann Chir Gynaecol 1991;80:188-201.
8. Maffulli N. Augmented repair of acute Achilles tendon ruptures using gastrocnemius-soleus fascia.
Int Orthop 2005;29:134.
patients with Achilles tendinopathy. Disabil Rehabil 2008;1-8.
10. Maquirriain J, Ayerza M, Costa-Paz M, Muscolo DL. Endoscopic surgery in chronic achilles
tendinopathies: A preliminary report. Arthroscopy 2002;18:298-303.
11. Marotta JJ, Micheli LJ. Os trigonum impingement in dancers. Am J Sports Med 1992;20:533-6.
12. Steenstra F, van Dijk CN. Achilles tendoscopy. Foot Ankle Clin 2006;11:429-38.
13. Thermann H, Benetos IS, Panelli C, Gavriilidis I, Feil S. Endoscopic treatment of chronic mid-portion
Achilles tendinopathy: novel technique with short-term results. Knee Surg Sports Traumatol Arthrosc
2009;17:1264-9.
14. Vega J, Cabestany JM, Golano P, Perez-Carro L. Endoscopic treatment for chronic Achilles
tendinopathy. Foot Ankle Surg 2008;14:204-10.
17
16
Achilles Tendinopathy – Open Surgical Treatment
“This was the most unkindest cut of all”
(William Shakespeare - Julius Caesar)
Chapter 16.
Achilles Tendinopathy -
Open Surgical Treatment
Rodney B. Hammett, Terrence S. Saxby
Take Home Message
• Most patients respond to non-operative therapy.

• Consider operative intervention only after failure of conservative measures.
• Surgical principles are removal of adhesions, excision of diseased paratenon,
decompression of the tendon by tenotomy and removal of abnormal areas.
• Augmentation is indicated if >50% of tendon bulk is resected.
Introduction
Disorders of the Achilles tendon have historically been poorly understood and,
despite extensive study, consensus on management remains elusive9. Numerous
treatment modalities are available, but the condition remains a source of
frustration to both patient and treating physician alike.
Painful conditions of the Achilles tendon are common. Often considered a
condition affecting athletes18, with an estimated incidence of 7% in runners,
one third of cases however occur in a more sedentary population41. It is useful to
distinguish between insertional and non-insertional tendinopathy27. Insertional
tendinopathy of the Achilles tendon occurs at the junction with the calcaneus
17
and may be associated with bony spurs. It will not be considered further in this
chapter.
Non-insertional tendinopathy occurs in the main body of the Achilles tendon
usually 2-6 cm proximal to its insertion. At this level, the tendon rotates internally,
the posterior fibres becoming more lateral, possibly producing excessive intra-
tendinous stresses. This area of the tendon has also been considered relatively
hypovascular14. Presenting symptoms and signs include pain, swelling, loss of
function, tenderness and crepitus.
Non-operative management modalities include primary prevention by altering
training practices45 or rest in the acute phase51. Activity modification, correction of
gait abnormalities or limb malalignment, orthoses, physical therapy (particularly
eccentric loading exercises1,23, pharmaceutical interventions26, corticosteroid
injection8 and extracorporeal shock-wave therapy39 have had varying degrees of
success. Eccentric exercises are most beneficial24.
Non-operative management is unsuccessful in one quarter to one third of
patients6,46,34. Twenty-nine percent of patients in a long-term follow up study
underwent surgery34.
Imaging
The decision to undertake should be based primarily on an appropriate history.

Physical examination findings, with appropriate imaging if necessary, may guide
the surgeon as to the most suitable procedure, of which many variations are
described.
Magnetic resonance imaging (MRI) and ultrasound (US) are useful to identify
the nature, location and extent of the lesion, although this information is often
elicited by careful clinical examination2.
Abnormal findings should be interpreted with caution and correlation with clinical
findings is essential as both MRI12,44 and US34 may demonstrate intratendinous
lesions in the asymptomatic contralateral side. Both modalities correlate with
outcome following surgery with high grades of abnormality being associated
with poorer outcomes2,12,30.
Ultrasonography demonstrates hypoechoic areas and increased sagittal
diameter, which is associated with a poorer outcome2. Ultrasound41 and MRI
appearance correlate with histopathology and are equally sensitive at identifying
intratendinous lesions2. Neither is able to predict accurately the presence of partial
tears identified at surgery2,32. Focal hypoechoic areas of failed healing response
are often reported as “partial tears” or “ruptures” which may be misleading9.
Neither US nor MRI are good at accurately identifying peritendinitis2,32.
Indications For Surgical Management
Patients may be selected for surgery based upon recalcitrant tendinopathy that
is interfering with daily or recreational activities. Patients should be considered
for surgical management after failure of an appropriate course of conservative
16
treatment. There is much disagreement on appropriate timing of surgery. Some

authors advocate surgery after only three months13. We would advise a period of
at least six to twelve months before operative intervention.
In 1977, Puddu described three distinct patterns of Achilles tendinopathy:
peritendinitis (Group I), peritendinitis with tendinosis, and tendinosis (Group II)40.
More recently, Maffulli et al suggested to abandon the ‘tendinitis’ and ‘tendinosis’
labels in the clinical setting, and to use instead the term ‘tendinopathy’. The terms
‘tendinitis’ and ‘tendinosis’ should be reserved to clearly defined and identified
histopathological features19. This suggestion seems to have been taken on board
by the scientific community, and an increasing number of authors has embraced
the tendinopathy terminology in favour of the ‘tendinitis’ and ‘tendinosis’ terms.
Most patients with peritendinopathy will settle with conservative management,

and if operative intervention is ultimately indicated, simple resection of the
diseased paratenon may suffice.
Surgical procedures for non-insertional Achilles tendinopathy fall into several
broad categories: open adhesiolysis, adhesiolysis with tendon debridement,
augmentation procedures, percutaneous tenotomy and other minimally
invasive techniques. Percutaneous tenotomy has been shown to produce results
similar to open surgery in selected cases with discreet lesions and the absence of
peritendinopathy20. This will be discussed further elsewhere.
Surgical Technique

The aim of surgery is to return the patient to their previous level of activity.
Informed consent is critical. Because of the nature of the condition and the
varied outcomes of surgery, patients should have realistic expectations of the
probable outcome and possible failure to improve and return to full sporting
activity. Patients should also be aware of the possible need for augmentation
after debridement and consent forms should state “Open debridement ± tendon
transfer”.
After the induction of general anaesthesia, the patient is positioned prone.
Because of this, we recommend marking the posterior aspect of the leg as
well as the anterior to avoid the possibility of wrong side surgery. A pneumatic
tourniquet may be applied to the upper thigh.
Most procedures use a straight longitudinal incision that may be placed midline,
medially42 or laterally. The choice may be guided by the site of previous incisions
or by the possible choice of procedure. We prefer the posteromedial incision as it
may avoid injury to the sural nerve.
The crural fascia is divided and the paratenon is exposed and incised longitudinally.
Open adhesiolysis and paratenectomy

For patients in whom frank tendon involvement has not been demonstrated
by preoperative investigations or intraoperative findings, adhesiolysis may be
performed with or without resection of the paratenon28,41. Adhesions between
17
tendon and paratenon are carefully divided. If the paratenon is inflamed or if

preoperative investigations suggest peritendinopathy, the paratenon may be
excised.
Open debridement
If preoperative investigations have demonstrated areas of central core
degeneration or surgical exploration has demonstrated discrete areas of
thickening or nodularity, a longitudinal tenotomy is performed.
Areas of abnormal tendon appear dull and yellowed, and may contain crystalline
deposits compared with the glistening white of normal tendon. Macroscopic
areas of tendinopathy are excised and thoroughly debrided. Defects may be
left open21, but the senior author prefers careful closure with an absorbable
monofilament suture with placing the knot within the tendon substance.
If the tendon is thickened but preoperative imaging or exploration does not
demonstrate discrete lesions, a series of smaller longitudinal incisions may
be made. This technique has been shown to initiate vascular ingrowth and a
healing response5,41. In all surgical interventions, the anterior attached fat pad
with “neovessels and/or nerves” should be dissected, as this is thought to be a
continuing source of pain.
Augmentation and reconstruction

After extensive debridement there is often enough tendon remaining to achieve
side-to-side closure of the tenotomy. However, if more than 50% of the tendon
has been debrided, we recommended its augmentation by one of the means
outlined below7,42. Small defects may be accommodated with a turn-down flap
and/or plantaris17, but larger defects require a tendon transfer. Suitable transfers
include peroneus brevis, flexor digitorum longus (FDL) and flexor hallucis longus
(FHL).
The choice of graft may determine the placement of the initial incision, although
the tendon of peroneus brevis may be accessed through a medial incision49. The
use of the tendon of peroneus brevis has been described in acute rupture of the
Achilles tendon38,48 and in patients with chronic tendinopathy49.
Both FHL7,50,52 and FDL25 transfers have been described for chronic rupture of the
Achilles tendon. Harvest may require separate medial incisions to release the
tendon at the knot of Henry52, separating it from the vincula with the tendon
of FDL, or, alternatively, FHL may be harvested through a small plantar incision
in the hallux, thus obtaining a greater length of tendon. Alternatively, an
interference screw may be used to anchor the tendon graft into the calcaneus
anterior to the Achilles insertion. A Beath pin is passed from a point immediately
anterior to the Achilles footprint and passed through the plantar aspect of the
calcaneus. Once an appropriately sized tunnel has been drilled the FHL tendon is
pulled through with a firmly attached suture. There are several advantages of this
method of fixation: It negates the need for a separate medial incision as a shorter
graft may be securely fixed; tensioning of the graft may be easier as the graft is
often difficult to pass through the calcaneus as back on itself; the doubled back
16
FHL graft plus residual Achilles tendon may be too bulky49. The FHL tendon may
also provide additional blood supply to the reconstruction.
The use of bone-tendon Achilles allograft has been described for neglected
ruptures29 of the Achilles tendon. It may be utilized to manage large defects
following extensive debridement or in patients in whom previous augmentation
procedures have failed. It requires an extensile approach and thorough
debridement of degenerate native tendon. A bony trough is produced in the
calcaneus to accommodate the bone-block and the graft rigidly internally
fixed. The tendon is secured in maximum plantarflexion. This technique has
produced reliable pain relief and incorporation, though it may stretch out during
incorporation49.
Achilles tendon defects in patients with a chronic rupture have been augmented
with a variety of prosthetic materials including carbon fibre36,37, Dacron15, Marlex
mesh (monofilament knitted polypropylene)31, collagen tendon prosthesis10, and
LARS tendon substitute16 with most favourable results. We have no experience of
this kind with chronic tendinopathy.
Postoperative Rehabilitation
Post-operative management needs to be tailored to individual patients based

upon operative findings, extent of debridement and whether reconstruction
has been performed. Most authors recommend a period of immobilisation
ranging from two to eight weeks, up to ten weeks in cases of reconstruction4.
The recommended position of immobilisation also varies from neutral to varying
degrees of plantarflexion.
When there has been minimal debridement, early mobilization of the ankle
may be allowed in order to prevent adhesion formation within the paratenon or
anteriorly from the fat pad.
Rehabilitation should be supervised with strength and range of motion exercises
as able. Return to sport tends to be at around the six month mark but should be
individualized and occur when strength returns.
As a general rule of thumb, patients with only minimal debridement may weight-
bear post-operatively as tolerated. All other patients should be immobilized
with protected weight-bearing for two weeks, or longer if the debridement has
been extensive, and has required augmentation. Sport-specific training may
commence at three months, competitive sport at six months22.
Results of Surgery
Success rates for the surgical management of non-insertional Achilles

tendinopathy are reported to be in the order of 75% to 100%5,13,28,42,43. This,
however, is often not experienced in day-to-day clinical practice. A systematic
review of 26 articles examining surgical outcomes evidenced a negative
correlation between the quality of the outcome and that of the methodology of
17
the study47.
The difficulties incurred in assessing the outcomes of surgery are compounded
by a lack of understanding of the natural history of the disorder and the lack
of prospective controlled studies comparing operative and non-operative
management. What studies we have available are of limited validity due to
deficiencies of study design and analysis47. Many of the existing studies are
retrospective and lack strict inclusion criteria and objective outcome measures.
In paratendinopathy, early surgery (three months) with adhesiolysis ± excision of
paratenon produces good to excellent results in over 96% of patients13, but these
results are not applicable to tendinopathy of the main body of the Achilles tendon.
Nelen operated later (18 months), with paratendinopathy patients receiving
adhesiolysis/paratenectomy, and patients with tendinopathy of the main body
of the tendon undergoing debridement ± a turndown flap. A success rate of
86% was reported in patients with paratendinopathy, and of 73% in patients
with tendinopathy. The patients who received a turn-down augmentation had
an 87% success rate28. Paavola demonstrated a significant difference in outcome
between patients with a focal intratendinous lesion to those without in terms of
success (54% and 88% respectively) and complication rate (27% and 6%)35.
Patient with chronic tendinopathy fare less well after surgery, and rates of
reoperation are higher. Of 14 patients who underwent surgery an average 87
months from onset of symptoms, only 5 had good or excellent outcomes, and six
required re-operation21.
Complications
Paavola et al presented the complication rates a large series of 432 consecutive
patients with rates of wound edge necrosis (3%), superficial infection (2.5%) and
sural nerve irritation (1%). Other complications included seroma, haematoma
and fibrotic reactions and one thrombosis33. Hence, in a very specialized centre
there is an 11% complication rate with a reoperation rate of around 3%. Rupture
has been reported after surgery for tendinopathy in a patient performing
eccentric loading exercises3.
Conclusion
There is insufficient evidence to determine the most appropriate treatment for

Achilles tendinopathy. A recent review by the Cochrane group identified no
studies of surgical management of sufficient caliber to include in their analysis26.
A review of 26 studies of surgical outcomes by Tallon et al acknowledged an
overall improvement in methodology over the last 20 years47.
It is not clear why tendinopathic tendons respond to surgery – the debate
revolves around surgically induced revascularisation and denervation11.
However the literature would support a step-wise approach to management
with surgery considered as a last resort after failed conservative treatment.
Surgery is indicated after an appropriate course of non-operative management
for at least six to 12 months. There may be a case for surgical intervention before
16
too much time has elapsed.

Peritendinopathy may require adhesiolysis with or without resection of the
paratenon. Tendinopathy requires debridement and, if this is extensive (i.e.
greater than 50% of the tendon resected), augmentation may be required. The
rate of success of surgical treatment is in the region of 75%, with better outcomes
in the milder cases with less extensive tendinopathy. Complication rates are not
insignificant with a tendency toward higher rates of complications in augmented
or more extensively debrided cases.
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2000;28:77-82.
34. Paavola M, Kannus P, Paakkala T, Pasanen M, Jarvinen M. Long-Term prognosis of patients with
achilles tendinopathy: An observational 8-year follow-up study. Am J Sports Med 2000;28:634-42.
35. Paavola M, Kannus P, Orava S, Pasanen M, Jarvinen M. Br J Sports Med 2002;36:178-82.
36. Parsons JR, Rosario A, Weiss AB, Alexander H. Achilles tendon repair with an absorbable
polymercarbon fiber composite. Foot Ankle 1984;5:49-53.
37. Parsons JR, Weiss AB, Schenk RS, Alexander H, Pavlisko F. Long-Term follow-up of achilles tendon
repair with an absorbable polymer carbon fiber composite. Foot Ankle 1989;9:179-84.
38. Perez TA. Traumatic rupture of the achilles tendon. Reconstruction by transplant and graft using
the lateral peroneus brevis. Orthop Clin North Am 1974;5:89-93.
39. Perlick L, Schiffmann R, Kraft CN, Wallny T, Diedrich O. [Extracorporal shock wave treatment
of the achilles tendinitis: Experimental and preliminary clinical results] Z Orthop Ihre Grenzgeb
2002;140:275-80.
40. Puddu G, Ippolito E, Postacchini F. A classification of achilles tendon disease. Am J Sports Med
1976;4:145-50.
1997;18:565-9.
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1987;15:308-15.
43. Snook GA. Achilles tendon tenosynovitis in long-distance runners. Med Sci Sports & Exerc
1972;4:155-8.
44. Soila K, Karjalainen PT, Aronen HJ, Pihlajamaki HK, Tirman PJ. High-Resolution MR imaging of the
asymptomatic achilles tendon: New observations. AJR 1999;173:323-8.
45. Stanish WD. Overuse injuries in athletes: A perspective. Med Sci Sports Exerc 1984;16:1-7.
46. Sundqvist H, Forsskahl B, Kvist M. A promising novel therapy for achilles peritendinitis: Double-
Blind comparison of glycosaminoglycan polysulfate and high-dose indomethacin. Int J Sports Med
1987;8:298-303.
47. Tallon C, Coleman BD, Khan KM, Maffulli N. Outcome of surgery for chronic achilles
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17
16
Tendinopathy of the Achilles Tendon Gene Therapy
“We used to think that our fate was in

our stars, but now we know that, in
large measure, our fate is in our genes”
(James Watson)
Chapter 17.
Tendinopathy of the
Achilles Tendon
Gene Therapy
Paul W. Ackermann, Paul T. Salo, David A. Hart
Take Home Message
• A number of growth factors delivered with gene transfer techniques have

demonstrated promising results to enhance tendon repair.
• As the defective healing mechanisms in tendinopathy are being elucidated new
targets for gene delivery can be developed.
• Promising targets for gene transfer in tendinopathy include PDGF, bFGF, BMP-
12 and BMP-14, possibly also genes for other growth factors such as NGF, VEGF,
and TGF-B as well as metalloproteinase inhibitors, and potentially also gluta
mate receptor inhibitors.
Introduction - Rationale for gene therapy
Tendinopathy is characterized by successive, “failing” healing responses leading

to molecular alterations, cellular aberrations, and finally micro- and macroscopic
visible adaptations of extracellular matrix molecules27.
Recent advances in cell biology have identified a variety of molecules, including
stem cells, growth factors and their receptors, involved in directing cell functions
during tendon repair1, 3. Experimental studies additionally indicate that local
application of growth factors is a promising therapeutic tool for optimization of
17
the repair microenvironment. Thus, tendinopathy, which exhibits pathologically

altered healing responses, would profit from therapeutic growth factor
interventions that augment the healing capacity while minimizing aberrant
tissue proliferation, with regard to angiogenesis, nerve ingrowth and scar tissue
formation.
The yet limited success of clinical trials with local application of peptide growth
factors emphasizes an important aspect of the tissue repair concept: the effective
delivery of these polypeptides to the repair site1, 30. A molecular approach by
which genetically modified cells synthesize and deliver the desired growth factor
in a temporally and spatially regulated manner to the wound site would be a
powerful means to overcome the limitations associated with local application of
growth factor proteins.
Prerequisite for gene therapy - characterization of tendon pathology
A well-defined temporal orchestration of cellular events is critical for repair1.

The combination of intrinsic factors (age, sex, genetic predisposition, diabetes
mellitus, rheumatic disorder) and extrinsic factors (tendon load and -frequency,
equipment, environment, occupation) leads to a disturbance of the tendon
homeostasis, i.e. delicate balance of cell, matrix and growth factor interactions27.
In tendinopathy, the swollen nonhealing tendon exhibits excessive tissue
proliferative reactions including scarring, angiogenesis and nerve ingrowth; an
abortive healing response that does not proceed to the remodeling phase. Recent
studies indicate that most cases of tendinopathy demonstrate a protracted nerve
ingrowth, expressing elevated levels of the sensory neuropeptide substance P
(SP)17, 29. SP is implicated in neuronal inflammation, and the pathological changes
demonstrate a substantial mast cell degranulation and expression of several
enzymes including proteinases and their inhibitors, in a sex-specific manner13,
14
. Thus, characterization of the micro-biological environment recalcitrant to
healing in tendinopathy is crucial for the development of efficient, specific local
therapeutic approaches.
There is increasing evidence that the persisting infiltration of mast cells,
macrophages and B- and T-lymphocytes during repair plays a major role in the
generation of a protease rich and pro-oxidant hostile microenvironment13,29.
Metalloproteinase enzymes are believed responsible for much of the
degradation of collagen and proteoglycan in tendinosis. Recent experimental
studies demonstrated that the metalloproteinases ADAM-12 (a disintegrin and
metalloproteinase) and MMP-23 (matrix metalloproteinase) are significantly
upregulated in tendinopathy27. In addition, proteolytic degradation-products,
generated by high protease activity in the chronic wound environment, may
exert inhibitory effects on cell function.
In summary, we need to identify deleterious factors that contribute to the non-
healing environment in order to further develop current treatment modalities.
Potentially, identified factors could provide novel therapeutic targets for gene
therapy. In addition to negating deleterious factors in tendinosis environments,
we also need to identify approaches to enhance recovery from such environments
16
and accelerate tissue repair and regeneration to restore pain-free function.
Gene-transfer Techniques
Gene delivery systems can be classified as either viral or non-viral. Advantages

and disadvantages of these technologies will shortly be discussed.
Viral techniques
On the whole, the technological strategy is to replace some or all viral genes with
the new gene of interest and thereby generate a replication-defective particle.
Viruses are in general capable of efficiently transducing cells and in some cases
permanently integrating into the host cell’s genome. The choice of viral type
depends to some extent on whether permanent or transient expression of the
gene product is desirable. Retroviruses, adenoviruses and adeno-associated
viruses are the most commonly used viral gene-delivery systems in general and
in soft tissue repair applications15, 24.
Non-viral techniques
There have been rapid advances in the development of physiological means
(non-viral) to introduce genes into target cells. Although non-viral gene transfer
is less efficient, recent studies indicate that effective gene transfer approaches in
tissue repair exert functional alterations at low level expression of the transgene.
Synthetic non-viral gene transfer systems have the advantage of delivering
genes to target cells without the disadvantage of recombining with wild type
viruses and with possible cellular damage due to repeated exposure to the viral
vectors. These synthetic systems are also easier to manufacture on a large scale
because they typically contain plasmid constructs that can be cultured with
existing fermentation technology. Direct plasmid application, lipofection and
receptor-mediated delivery vectors are the most promising non-viral systems.
17
Vector Type Maximum Advantage Disadvantage

gene size
Viral
Retrovirus RNA 6 kbp Genes can be transferred to a wide Risk of vector-induced target cell
range of different cell types transformation
Genes are efficiently
transferred
Genes are stably integrated into
the chromosomal DNA
Adenovirus DNA 37 kbp The highest gene transfer Cytotoxic

efficiency in vivo Immune responses
Transduction of non-dividing cells
Adeno- Single 5 kbp Considered to be the safest Difficult to manufacture

associated stranded DNA Transduction of non-dividing cells Immune responses
viruses
Herpes simplex Double 30 kbp Primarily a vector for gene transfer Cytotoxic
stranded DNA to the nervous system
Transduction of non-dividing cells
Non-viral
Plasmid DNA Technologies include: direct Low transfection efficiency

injection, particle mediated gene
transfer, microseeding, and
electroporation
Inexpensive, Safe, Non-
immunogenic
Liposomes Few Inexpensive, Safe, Transient gene expression

constraints Non-immunogenic
Nanoparticles Few Can incorporate complex functions,

constraints including controlled release,
targeting and encapsulation. Both
viral and non-viral DNA can be
incorporated.
Parenteral, local, or inhalant
delivery
Table 1: - Gene vectors.
Gene therapy can be employed via either an in vivo or an ex vivo approach.
Ex vivo gene transfer

In an ex vivo approach, specific cells are harvested from the patient, and then
genetically manipulated outside the body; the transduced cells are then
reimplanted into the tendon. Further, the ex vivo approach allows enhancement
of the function of gene modified cells by combining modified cells with
biomaterials which support cell function prior to transplantation. For instance,
mesenchymal stem cells can be isolated from a non-tendon source and then
transfected with a specific gene prior to reintroduction to a tendon with or
without differentiation.
16
In vivo gene transfer

In vivo gene therapy eliminates the need for proper cell culture and
transplantation, since the genes are delivered directly into the target tissue. This
method simply requires that the DNA vector, harboring the encoding sequence,
be inserted into host cells in vivo. This approach is especially applicable to tissues
where cells are difficult or impossible to culture and/or transplant, such as in the
nervous system. Although there are clear advantages of this in vivo approach,
it is sometimes difficult to target genes to specific cells of a particular tissue in
vivo. This is particularly true for dense connective tissues such as tendons or
ligaments,12, 22 but it can exert tangible effects on healing tissues.
Vehicle for vector transfer

Genetic approaches to tissue repair are based on the efficient delivery of the
vector/modified cells to the wound site, which is dependant on the vehicle
in which the vector/transgenic cells are incorporated. The transgene can be
delivered as a solution or as part of a scaffold matrix of natural or synthetic origin.
Porous biomaterial scaffolds have been shown to promote the gene transfer
efficiency by providing the surface on which cells and DNA vectors interact.
Recently, the potency of different biodegradable carriers to serve as in vivo gene
delivery media has been investigated. Type I collagen (lyophilized sponge, paste,
and gel), hyaluronan, chitin (and derivatives), and alginate can be used as matrix
carriers of plasmid DNA, as well as synthetic materials such as poly(lactide-co-
glycolide), carboxymethylcellulose and other nanoparticles containing synthetic
polycationic polymers or polymers conjugated with molecules to direct delivery
(e.g. with folate to direct to folate-receptor positive cells) and enhance uptake
of the vectors. Such gene delivery systems are referred to as gene activated
matrices, and these activated matrices have been found not only to optimize in
vivo vector delivery but also to limit gene transfer to those cells which actively
invade an artificial scaffold10.
Regulation of transgene expression
A successful gene therapy strategy relies not only on the efficient delivery of the
transgene into the target cell, but also requires maximum control over localization
and duration of transgene expression. One strategy to control transgene activity
is achieved by inserting tissue-specific or inducible promoters into recombinant
vectors.
17
Gene therapy in tendon repair
Gene Vector Model Evaluation Results Reference
BMP-12 Adenovirus Transected rat Biomech., hist. Maximum failure load Majewski et al 200819
Achilles tendons 1, 2, 4, 8 w increased at 1 week
Tendon stiffness
increased at 1, 2 and 4
weeks
More organized
collagen fibers at all
time points
BMP-14 Adenovirus Rat Achilles Biomech., hist. Tensile strength Bolt et al 20074
(GDF-5) tendon 1, 2, 3 w increased 70% at 2
laceration weeks
No adverse response
bFGF Plasmid Tenocyte Expression of type I Increase expression of Feng et al 20077

and III collagen type I
RT-PCR and III collagen mRNA
GDF-5 Adenovirus Rat tenocytes RT-PCR, Western Maximum in vitro Rickert et al 200526
(BMP-14) Transected rat blotting and GDF-5- GDF-5 secretion at 2
Achilles tendons ELISA weeks
Biomech., hist. Maximum in vivo GDF-5
expression at 4 weeks.
A trend to higher
strength with GDF-5 at
8 weeks
bFGF Adeno- Rat intrasynovial Expression of bFGF Increased expression Wang et al et al 200532
associated tenocytes and type I and III of bFGF, type I
virus collagen genes. and III collagen
RT-PCR mRNA
AdGFP Adenovirus Fore- and 3 different viral titers Dose-dependent Mehta et al 200521
marker hindpaw transgene expression
gene or tendons of at 12 days
BMP-13 rabbits Highest dose gave
(GDF-6) notable lymphocytic
infiltration
PDGF Liposome Rat intrasynovial Expression of type I Increased expression Wang et al 200431
tenocytes collagen gene. RT-PCR of type I collagen
mRNA
LacZ marker Plasmid Achilles tendons LacZ expression No more gene Jayankura et al 200316
gene of rat and mouse, 2, 8, 14, 21, 28, 42 days expression at day 42.
and the patellar Electrotransfer No inflammatory
tendons of rabbit reaction was
observed.
Gene transfer
improved 50% under
certain electrical
conditions.
Multiple injections of
plasmid increased
the number of
transduced cells by
400%
Table 2: Gene transfer to tendons.
16
Gene Vector Model Evaluation Results Reference
LacZ marker Adenovirus In vitro human LacZ expression Duration of LacZ Dai et al 20035
gene rotator cuff Gelatin sponge expression was 6 days.
tendon cells 100% transfection rate
In vivo rat at 5000 PFU/cell.
Achilles tendon In vivo LacZ expression
healing was 17 days Transfection
efficiency was enhanced
threefold with a gelatin
sponge as matrix
BMP-12 Adenovirus Lacerated Alkaline phosphatase In vitro increased type I Lou et al 200118
(GDF-7) chicken tendon activity Biomech collagen synthesis.
In vivo two-fold increase
of tensile strength and
stiffness of repaired
tendons
Decorin Haemaggluti- Injured rabbit Transmission electron Larger collagen fibrils in Nakamura et al 200122
Antisense na-ting medial microscopy, Biomech early scar.
virus of collateral Tensile strength
Japan (HVJ) ligament increased 83-85% at 6
-liposomes weeks.
33-48% less irrecover-
able creep under
loading
Marker gene HVJ- Intra arterial 3, 7, 14, 28 and 56 Transfection rate 12.1%, Ozkan et al 200025
liposomes delivery days 8.7%, 10.2%, 3.2% and
Transected rat 0.7% at post-injection
patellar tendon days 3, 7, 14, 28 and 56
PDGF HVJ- Injured rat Hist. Enhanced expression Nakamura et al 200023

liposomes patellar tendon 1, 4 and 8 weeks of PDGF up to 4 weeks
after transfection,
Initial promotion of
angiogenesis and
subsequent enhanced
collagen deposition
LacZ Marker Adenovirus, In vitro and in Hist. Adenovirus was the Gerich et al 19979
gene AAV, vivo rabbit most effective vector.
Retrovirus, patellar tendon Liposomes showed
Liposomes low efficiency. Trans-
duced cells could be
observed over a
6-week period
LacZ Marker Adenovirus In vitro and in Hist. Adenovirus injections Gerich et al 19968
gene Retrovirus vivo rabbit resulted in high levels
patellar tendon of lacZ expression.
Allotransplantation of
tendon fibroblasts into
which the lacZ gene
had been retrovirally
introduced led to lacZ
expression throughout
the body of the tendon
itself
Despite the still daunting lack of data regarding the normal events of tendon
healing, since 1996 there have been 14 pioneering studies published that
collectively demonstrate the considerable promise of gene therapy for improving
tendon healing. The important aspects of each study are listed in Table 1. Initial
reports focused on determining the feasibility of achieving gene transfer into
cultured tenocytes, using the lacZ reporter gene, establishing the adenovirus or
adenoassociated virus as preferred vectors.
17
As others have found, the adenovirus vector is efficient, but it does generate
an immune response, and sustained expression of the candidate gene beyond
a few weeks has not been achieved. Adenoassociated virus appears to be
less immunogenic and thus, may be a preferable choice of viral vector. Other
investigators have used liposomes or plasmids as vectors, but have noted low
efficiency of transfection unless adjunctive methods such as eletrotransfer or the
use of a gelatin sponge as matrix are used to increase entry into the cell.
As experience and confidence with these techniques grows, there has come the
realization that 100% efficiency of transfection and a prolonged expression of a
candidate gene may not be necessary to achieve a significant treatment effect.
To date, only BMP-12 and BMP-14 (GDF-5) have been utilized in tendon tissues
that have subsequently undergone functional testing, and each has induced
significantly increased tensile strength in the healing rat Achilles tendon. The
field remains in its infancy, but feasibility has been established and further
refinements of delivery techniques, a broader choice of candidate gene(s) and
more sophisticated and longer term outcomes testing are certain to come.
Establishing the feasibility of these techniques for the treatment of tendinosis
has been hampered by the lack of an established animal model. However,
given that spontaneous tendon ruptures are always preceded by clinically
silent tendinopathy, the establishment of an effective therapy would offer the
opportunity to intervene early enough to prevent a majority of these serious
injuries.
Candidate genes for repair in tendinopathy and clinical considerations
While gene therapy has been applied to overt tendon repair after injury, there
are a number of issues that have to be addressed when selecting candidate
genes to both inhibit the degenerative processes associated with tendinosis, as
well as enhance the repair of the damaged tissue to restore function. Some of the
important issues and assumptions are the following:
1. Unlike connective tissue healing which is fairly well characterized, the process
leading to tendinopathy is less well defined, and there may be variability in both
the process (involving genetic considerations, age, sex, time post-initiation,
symptoms), the stage that any one individual is at the time of intervention, and
tendon-specific considerations. Thus, the tendinopathy progression process
in the patellar tendon, Achilles tendon, and the supraspinatus tendon may be
very different due to the nature of the tissue, the loading environment, and the
tendon history.
2. How many genes are required to overcome a complex degenerative process
effectively? The concept of the “magic bullet” approach to identify the ideal
candidate gene is likely flawed based on the complexity involved. Therefore,
effective gene therapy may require a “multiplex” approach with specific proteins/
peptides, or alternatively an anti-sense or siRNA approach may be required to
down regulate negative elements that are expressed and one or more “positive”
transgenes to enhance recovery/repair.
3. The age of the individual may also play a role in selecting candidate genes as
16
it is well known that repair process decline with age. Furthermore, for female
athletes and others affected by tendinopathy, age has another influence, as
menopause and sex hormones are also known to influence both repair processes
and the set point for connective tissues11.
4. What outcome is acceptable? Is it regeneration with restoration of a high level
of performance, or is repair that permits normal everyday life experience with no
symptoms satisfactory?
5. Are there suitable experimental models available that accurately mimic human
tendinosis so the approaches can be validated prior to human studies?
6. Are there suitable delivery systems available to allow testing of the effectiveness
of candidate genes? The best candidate genes will be ineffective if they cannot
be delivered effectively for the required period of time.
Given the above considerations it may appear to be a daunting task to identify

appropriate candidate genes and an effective delivery system. However, based
on the gene therapy experiments that have demonstrated enhancement of
tendon repair (see Table 2 for summary), the growth factor genes for PDGF,
bFGF, BMP-12 and BMP-14 may possibly be good candidates also for promotion
of repair in tendinopathy due to their pleiotrophic impact on cells in tendons.
Genes for other growth factors (eg NGF) 20 and their receptors, as well as for other
repair stimulating molecules, i.e CTGF, VEGF, TGF-beta, could also be interesting
candidate genes in tendon repair.
However, stimulation of repair in normal tendon healing and in tendon pathology
may be two different issues. Thus, an alternate strategy would be to identify over-
and under-expressed genes in tendinopathy and to direct the gene manipulation
to these pathways.
Since several metalloproteinases, i.e. ADAM-12 and MMP-23, have been
demonstrated to be up-regulated in tendinopathy, the administration of
recombinant metalloproteinase inhibitors or specific anti-sense/ siRNA
reagents may promote repair in tendinopathy by downregulating the influence
of the negative components of the degenerative process. In fact, TIMP-2, a
metalloproteinase inhibitor, has been demonstrated to promote tissue repair6.
Since many of the molecules potentially involved have somewhat short half-
lives, one may have to envision chronic delivery systems (e.g. implanted osmotic
pumps) for some of the multiplex protocols as opposed to a single bolus
approach.
Another pathway that has been demonstrated to be overexpressed in
tendinopathy is the neuronal pathway2. Thus, tendinopathic patients exhibit
increased levels of sensory neuropeptides, glutamate and the glutamate
receptor, N-methyl-d-aspartate receptor type 1 (NMDAR1), which is implicated
in tendon pain and known to trigger a variety of chronic pain disorders28. Thus,
recombinant glutamate receptor inhibitors could presumably alleviate the pain
symptoms and may also enhance repair.
From this discussion, it is clear that choosing the ideal candidate gene will
require additional knowledge regarding the actual molecular and cellular events
leading to initiation of the process leading to what is defined as tendinopathy,
17
as well as development of appropriate and effective delivery systems to ensure

that the candidate genes can impact the tissue optimally. Data obtained from a
variety of studies conducted thus far has identified some candidate genes, but
additional studies based on gene array analysis, in situ hybridization analysis
to find out which cells are being affected by the process, and careful study of
affected areas of tendons (e.g. using laser capture technologies) should led to
identification of further candidates. Obviously, lessons learned from some of
big Pharmas failures to address complex conditions such as osteoarthritis using
single molecule approaches (whether it be to inhibit degenerative processes
or stimulation of repair processes) should be kept in mind as the gene therapy
approach continues to evolve and develop to treat tendinosis.
References
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17
16
The Future: Stem Cell Therapy, Optimization of Healing
“Si jeunesse savait; si vieillesse pouvait.

– If youth knew, if age could.”
(H. Estienne)
Chapter 18.
The Future: Stem Cell

Therapy, Optimization
of Healing
Francesco Oliva, Nicola Maffulli, Nicholas R. Forsyth
Take Home Message
• Tendons have limited capacity for healing.

• Cell therapy could be used as an alternative or in addition to traditional tendon
therapy.
• Successful in vitro tenogenesis may require a combination of cells,
mechanotransduction, scaffolding, and growth factor cocktails.
Introduction
Tendon injuries are common in either the workplace or sport. There are
approximately 2 x 105 tendon and ligament repairs performed annually in the
U.S.A43. These can occur through injury and trauma, but also through overuse and
ageing, with histological features of a failed healing response or degeneration.
These injuries are difficult to manage, and frequently result in long-term pain and
discomfort, and place a chronic burden on health care systems53. Most frequently
injured are the patellar and the Achilles tendons, with pathology ranging from
calcifying tendinopathy, to partial tears, to complete ruptures27,55.
Tendons have limited capacity for self-healing75. Management of tendon injury
currently follows two routes: conservative or surgical. Conservative management
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generally revolves around rest and pain relief, but can also include injection of
a variety of drugs, including steroids, physical modalities, and physiotherapy.
Problems arising from conservative management include prolonged treatment
times, possible weakness in the affected area, recurrent injury, and partial loss of
function. Surgical options are frequently considered in serious injuries. Surgery
can be performed using either percutaneous or open techniques, and, when
damage is extensive, grafts may have to be used37. However, allografts are not
widely available, can be expensive, and carry risks of infection and rejection30.
Autologous grafts are associated with some degree of donor morbidity69. Where
healing of the lesion does occur, it does not result in full restoration of function,
and rehabilitation is extensive and intensive54.
The inability of the tendon to self-repair and the general inefficiencies of current
treatment regimes suggest make identifying alternative strategies a priority.
The tendon itself is relatively cell-poor, with a low turnover rate, and insufficient
capacity for self repair/regeneration. We discuss and describe current state-of-
the-art knowledge in tendon development, molecular knowledge of tendon
(biomarkers, differentiation, and transcriptional cascades), and stem cell
applicability to tendon repair strategies.
Biomarkers
The identification of the transcription factor Scleraxis (Scx) has helped greatly to
illuminate key components in the later development of tendons51. Scx is a marker
of tendon progenitor cells, and is detectable in specific somitic compartments,
as well as mature limb tendons12,51. This developmental perseverance, though
derived from animal models, argues towards the applicability of Scx as a marker
of a tendon-capable cell in human studies. Initial studies into Scx focussed on
the axial skeleton, but later studies using transgenic animals have demonstrated
that these Scx-positive progenitor cells are also found in limb buds associated
with the appendicular skeleton44,46. More recent studies have demonstrated that
the development of these tendon groups is likely to differ substantially. Using of
Scx -/- null mice, Scx expression has been shown to be essential for the correct
development of all force-transmitting and intermuscular tendons but not for
anchoring tendons38. This argues for the presence of distinct tendon-capable
progenitor cell types which are reliant on substantially different signalling
pathways and which emerge independently. Of additional note and potential as
a biomarker for de novo tenogenesis is myostatin (GDF-8). GDF-8 deficient mice
have small, brittle, and extremely hypocellular tendons. Furthermore, GDF-8 null
mice displayed significantly reduced Scx expression overall. Though temporally
distinct, there are now three identified factors with the potential to regulate Scx:
FGF-4, FGF-8, and GDF-819,36. Controlled expression of these factors could be the
key to controlling de novo tenogenesis in in vivo repair strategies.
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Stem Cells for Tendon Therapy
Several main types of stem cells are currently described: embryonic stem cells
(ESC), cord blood stem cells (CBSC), and adult stem cells (adipose-derived stem
cells (ADSC), bone marrow aspirate-adherent fraction stem cells (MSC) etc)23,24,45,60.
These stem cell types vary in their capacity to form different cell types. Broadly,
the hierarchy runs from the pluripotent ESC to the potentially pluripotent CBSC,
to the multipotent MSC. Surprisingly, neither CBSC nor ESC has described an in
vitro capacity to differentiate into either tenocytes or tendons.
In principle, the primary sources of human cells for therapeutic repair are
autologous (tenocytes, tendon progenitors, and adult stem cells), allogeneic
(tenocytes, tendon progenitors, adult stem cells, CBSC) or from other sources
(ESC).
Autologous
Tenocytes represent an obvious cell choice. Tenocytes, derived from tendon
progenitors, secrete large amounts of collagens which aggregate into basic
tendon fibrils56. Two primary problems with the tenocyte as a cell therapeutic for
tendon repair are: 1) tendons are relatively acellular, containing few tenocytes;
and 2) tenocytes do not proliferate for long in in vitro culture, and, during this
period, they de-differentiate and lose the characteristic tenocyte morphology75.
It remains unclear if a re-differentiation capacity remains after this point. An
alternative autologous option to the tenocyte could be the tendon stem/
progenitor cell (TSPC)9. This unique population of cells has been identified
in patients up to the age of 12. These cells are multipotent and capable of
regenerating tendon tissue, in animal models, after transplantation. It is not clear
at this time whether TSPC persist into mature adulthood or are a pre-adolescent
feature. What is clear is that these cells exhibit a requirement for a niche featuring
two structural components, Biglycan and Fibromodulin.
Adult stem cells present themselves as good candidates for autologous cell-
based tendon regeneration. MSC have been described as being tendon-capable.
However, these descriptions originate almost entirely from animal model studies
involving mouse, rabbit, rhesus monkey, and horse5,26,57,68,45. The horse provides
the proof of principle model that MSC can produce tendon tissue, and that cell
therapeutics can provide repair back to a pre-injury level. The scarcity of data
regarding human stem cell capacity to form tendon-capable cells or tendon
itself makes conclusions relatively difficult to draw. At present, there is a single
report, to our knowledge, describing the differentiation of hMSC into tenocytes
or tendon tissue. Upregulation of Scx and histological staining consistent with
tendon has been described from hMSC placed into dynamically loaded collagen
constructs32. We anticipate that these descriptions will increase over the coming
years.
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Allogeneic
There are no data regarding the differentiation of CBSC or ESC into tenocytes.
In the latter instance, ESC participate developmentally in chimeric animals10,
although we know of no instances where targeted tendon differentiation has
been demonstrated. Much work remains to define the optimal in vitro expansion
and differentiation of tendon cells and their progenitors.
Scaffolding
A second area requiring attention is the in vitro reconstruction of tendon

physiology in a manner suitable for transplantation. Tendons are three
dimensional structures with a clearly defined architecture and composition.
The development of acellular scaffolding which mimic tendon structure as
both accelerant and guide for de novo in vitro tendon formation has received
attention from a number of research teams4,6,22,34,40,41,47,50,59,76. Scaffolds fall into two
general categories: natural and synthetic. Natural scaffolds tested to date include
collagens, small intestinal sub mucosa, chitosan, renal capsule matrix, and silk
fibres4,6,22,34,41,47,59,76. Alternatively, synthetic scaffolds have been derived from
poly-L-lactic acid, modified poly(DL-lactide-co-glycolide) (PLGA)50. It remains
unclear what the optimal scaffolding design should be, what forces should be
applied, over what distance, and at which frequency. Both natural and synthetic
scaffolds are reported as increasing ECM deposition over controls. Chitosan-
based scaffolds in perfusion bioreactors and knitting PLGA nanofibres around a
PLGA scaffold are examples of both instances6,50.
Molecular Approaches
One of the difficulties in studying tenocytes, tendon progenitors, and their

associated behaviours has been the lack of clearly defined molecular markers.
The molecular footprint of tendon-capable progenitors through to differentiated
cells is now beginning to emerge. In the developing limb bud, all mesenchymal
cell lineages derive from a common precursor Sox9 positive population2. From
this initial population, all mesenchymal lineages develop, including tendon,
synovium, chondrogenic, osteogenic, and supporting stromal cells. The tendon-
capable cells which emerge at this time are generally characterised by the
positive expression of Scx through. Mature tendon cells can be characterised by
the expression of some general, and loosely specific, markers including tenascin,
tenomodulin, and the spatial orientation of Connexin 32 and 4311,65,67. At least one
of these markers, tenomodulin, lies under the direct transcriptional control of
Scx, as evidenced in overexpression studies56. Tenomodulin expression is tightly
regulated, and is found in tendons, cartilage, and nerves28,49,65. Tenomodulin
has been described as a tendon differentiation marker and as being necessary
for tenocyte proliferation and maturation18. Understanding the transcriptional
cascade behind Scx may therefore allow control over the production of in vitro
tendon-capable cells and tendon tissue.
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Transcriptional control of Scx in MSC and tenocytes is dependent on BMP-

signalling and Smad821,26,68,74,68. Studies performed in murine MSC lines have
demonstrated that coexpression of BMP2 and Smad8 results in cells with an
in vitro resemblance to tendon cells and in vivo repair capability26. Similar
studies using rhesus monkey-derived MSCs demonstrated that overexpression
of BMP12 (GDF7) resulted in tenocyte differentiation68. In both these studies,
Scx upregulation was observed. Paired studies suggest that BMP12 or BMP13
stimulates human tenocyte in vitro proliferation21,74. BMP2 is more commonly
associated with osteogenesis in hMSC, but there are, as yet, no descriptions
regarding the effects of BMP12 or BMP1335,42. Nonetheless, a molecular cascade
is emerging, running from BMP-signalling through to Scx activation and hence
tenocyte differentiation.
Growth factors
Numerous growth factors are involved in tendon repair in adults. These include
BMPs, EGF, FGF1, FGF2, IGF-I, IGF-II, PDGF-AA, PDGF-BB, PDGF-AB, TGF-β. These
may be produced locally by cells in areas of injury, growth and repair, or may
be delivered by blood. Exogenous supplementation of these factors in failed
healing responses, such as in resistant tendinopathies, may lead to a definitive
healing response.
Bone morphogenetic proteins

Bone morphogenetic proteins (BMPs) are a group of factors of the TGF-β
superfamily that stimulate bone formation but also stimulate tendon cell
mitogenesis and tendon healing. It is likely that the combinations and timings of
BMP signalling are crucial for tendon healing. For example, the observation that
BMP-14 knockout mice exhibit a delayed tendon healing response is reinforced
by the rat model, where it is required for the maintenance of homeostasis of
mature tendons16,20. However, in the rat Achilles tendons injury models BMP-13
was involved in early tendon healing and BMP-12 was required for both (healing
and homeostatis). BMP-12, BMP-13 and BMP14 have all been detected in intact
human tendons by immunohistochemistry17,21. In addition, BMP-2, BMP-7, and
BMP-12 all participate in tendon-bone healing and improve formation of new
bone and fibrocartilage at the healing tendon attachment site, resulting in
improved load to failure48.
Insulin-like growth factor

The stimulatory effects of IGF-I have been demonstrated in tendon cells on
migration, mitogenesis, matrix synthesis, and repair models1,8,33,61,64.
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Platelet-derived growth factor

Early supplementation (Day 3) of PDGF for tendon repair is not beneficial as
compared to supplementation at later time (Day 7)14. This probably resulted from
an increase in cell proliferation without matrix production. PDGF holds particular
promise in combination with other growth factors. Tendon cells express the
receptor for PDGF, but do not normally express PDGF itself64. When applied in
tandem with IGF-1, robust stimulation of tendon fibroblast, cell migration and
cell division are produced1,8. Moreover, serum, which contains both PDGF and
IGF-I, stimulates cells in the whole tendon both mitogenically and matrigenically,
and synergistically with cyclic load7. Taken together, these suggest that PDGF
and IGF-1 may exert a positive influence on tendon and ligament healing
through stimulation of cell proliferation, differentiation and matrix formation.
Additional studies demonstrated that the matrix formation was likely stimulated
predominantly by PDGF66.
Transforming growth factor beta

TGF-β has numerous physiological effects15,58. The expression of TGF-β appears
closely tied to the development of a differentiated phenotype in many cell types
including the mesenchymal precursor. Tendon and ligament formation has been
tied directly to factors belonging to the TGF-β superfamily70. TGF-β promotes
weak stimulator of tendon cell migration and mitogenesis, robust expression of
extracellular matrix and gene expression primarily through the activation of the
Smad signaling pathway although independent routes have been suggested63.
In a flexor tendon injury model, TGF-β was detected at and proximal to the repair
site, while in an Achilles model failure load and stiffness of the healing tendon
were increased by administration of TGF-β129,62. Furthermore, the application of
TGF-β1 significantly increased the tangent modulus and the tensile strength of
the fibrous tissue produced in a patellar tendon model, after resecting the central
portion, suggesting a role of TGF-β1 in in vivo tendon regeneration3. All three
TGF-β isoforms significantly increase collagen I and III production in cultured
tendon fibroblasts; TGF-β1 induced the greatest contraction13,31. This might
explain the finding that TGF-β1 induces scar tissue formation, whereas TGF-β3
reduces it52. Further distinction was provided with the demonstration that, while
exogenous addition of TGF-β1 increased human patellar tenocyte contraction
TGF-β3 promoted reduced contraction13. This reinforces the suggestion that,
while TGF-β1 promotes scarring, TGF-β3 can improve the mechanical properties
of healing tendons. Tendons, specifically the epitenon, tendon sheath and repair
sites, express the three TGF-beta receptor isoforms (RI, RII, and RIII), and all are
up-regulated after injury and during repair39.
The determination of this molecular cascade coupled to the increased knowledge
surrounding growth factors generates avenues for exploitation which could be
utilised for driving tenocyte differentiation. A number of standard mesenchymal
lineage differentiation protocols (chondrogenic, osteogenic) rely on the inclusion
of glucocorticoids in the chemical cocktail. However, both dexamethasone
and triamcinalone inhibit tenocyte proliferation, and induce apoptosis when
administered at even low doses25,73,71,72. The production of protocols to derive in
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vitro tenocytes from stem cells coupled to optimisation of culture conditions/

supplementation can be expected to yield high quality functional material for
use in in vitro tendon generation or direct application to damaged tendons.
Conclusion
The challenge of repairing damaged tendons is ideally suited to a stem cell-

based therapeutic. Poorly vascularised, acellular and with little regenerative
potential, the tendon requires alternative strategies to be developed. Research
is now beginning to unravel transcriptional control of tendon differentiation,
stimulation of stem cell tenocyte differentiation, and maintenance conditions
for optimised in vitro expansion. The ongoing stem cell influenced regenerative
medicine can be expected to impact directly on the tendon in coming years.
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Sport Specific Issues
“Train, don’t strain”
(Arthur Lydiard)
Chapter 19.

Maayke N. van Sterkenburg, Jón Karlsson, C. Niek van Dijk
Take Home Message
• Achilles tendinopathy is especially common in runners and badminton players.

• Overuse is thought to be the major cause.
• Advice for prevention includes adaptation of training methods and
optimization of muscle strength, flexibility, and shoe-wear.
Introduction
Achilles tendinopathy is a difficult to manage chronic problem. In approximately

70% of cases it occurs in patients who are sports-active on a recreational or
professional level. Thirty percent of patients have a sedentary lifestyle, however.
This is of interest, as obviously not all Achilles tendinopathies are correlated
with overuse or tendon injury. Irrespective of injury-related tendon damage,
biological changes in and around the tendon do occur.
Because of the increasingly common keep-fit culture, the incidence of chronic
Achilles tendinopathy is rising. Concerning the exact aetiology of Achilles
tendinopathy, several theories have evolved over time. Decreasing vascularisation
on aging, male gender, decreasing flexibility and strength of the triceps surae
muscle, obesity and foot deformities are some of the intrinsic factors
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predisposing to tendinopathy. Extrinsic factors may play a role as well, for

instance change of training intensity, poor walking/running technique, improper
shoe wear and walking on slippery surfaces.
Unfortunately, large reliable studies on the epidemiology of tendon injuries are

still lacking. Useful data from observational studies have been recently published,
however2, 3, 6, 8, 11-16, 18, 20, 23, 27, 30-36, 44. According to these studies, Achilles tendon
overuse injuries occur more often in certain types of sports, such as running,
tennis and badminton. In this chapter, we discuss epidemiology and aetiology
of Achilles tendinopathy, define risk factors, and make recommendations for
prevention of Achilles tendon problems in specific sports.
Epidemiology
Various epidemiological studies of recreational and competitive runners have

estimated that between 27% and 70% of runners sustain overuse injuries during
any one-year period23, 23, 33, 33, 34, 34, 35, 44. Biedert and co-workers treated 102 patients
with Achilles tendon problems during 3 years, of which 48% were runners, 15.7%
soccer players, and 5.9% tennis players2. Mazzone stated that Achilles tendon
problems occurred in 10% of runners during their life36. Clement and Taunton
found similar numbers, as Brubaker did with 11.9% of runners visiting his clinic with
‘tendinitis’, of which 69.2% was in the Achilles tendon6, 11. In professional athletes
in general, it has been claimed that overuse injuries occur in 7- 9% 25. Kujala and
co-workers reported a cumulative incidence of chronic Achilles tendon injuries
before the age of 45 of 42%, compared with 3% in the sedentary population30.
Badminton players are also at increased risk of chronic Achilles tendon injury.
Fahlström and co-workers found that 32% of elite players reported an episode of
a disabling painful condition in the Achilles tendon region during the previous
5 years14. Of middle-aged competitive badminton players, 44% reported pain in
the Achilles tendon region during the past 5 years15. The occurrence of Achilles
tendon injuries in athletes increases with age3, 15, 20, 31, whereas training quantity
was the only factor significantly related to Achilles tendon pain in a study on
younger elite players14. Another study described a cohort of 257 injuries, of which
20 were Achilles tendon injuries27. In a study by Groenewegen, a large group of
patients (n= 1200) of a sports- medical advisory center was reviewed, of which
13% had some kind of Achilles tendon problem related to sporting activities18.
There is an expanding group of ‘adventure racers’, a growing popular sport in the
United Kingdom, where mountain biking and canoeing are the main activities.
In 12.1% of subjects participating in these sports, Achilles tendon injuries are
reported during their life16. In recruits from the Military academy in the USA, an
incidence of 0.39 per 1000 days at risk was reported for Achilles ‘tendinitis’ (2.8%),
accounting for a third place of foot and ankle injuries. Surprisingly, this injury was
not found in any of the female recruits32. Hence, the conclusion may be drawn
that male gender is a notorious predisposing factor with reported proportions of
41:25 (male: female) in badminton players, and 75:22 and 78:22 in long-distance
runners8, 12, 15.
16
To put these figures into perspective, only 2.1% of 469 junior figure-skaters had
an Achilles tendon injury13.
Risk factors for Achilles tendinopathy
The exact causes of overuse injuries have yet to be determined, but it can be
stated that it is multifactorial and diverse in the sports-active35, 39, 43. In this part,
we report the main etiological/risk factors.
Overuse
The most commonly reported cause of injury to runners is ‘too much, too soon’
15, 31
. Fahlström changed this statement into ‘too much all the time’, due to the
fact that a high weekly training load was the only factor that correlated with pain
in the Achilles tendon region in his study. James and co-worker reported that
50% of running induced injuries in their study was caused by training errors.
Errors can be excessive intensity and duration of running, and are commonly
associated with a failure to allow physiological adaptation24.
However, it is unlikely that an elite runner would have progressed to a professional
level with poor running technique.
Also, training mileage is a known risk factor for lower extremity injuries in
exercising adults4, 5, 7, 21, 23, 29, 33-35, 37, 45. Hootman and co-workers found that running
over 20 miles/week increased the risk of lower extremity injury by 71% in men
and 112% in women45. Loss of fitness because of winter-stop or pre-season after
which activities are not resumed at slower pace is also a predisposing factor for
Achilles tendinopathy19.
Previous injury
Previous lower extremity injuries (mostly foot (22%) and knee (24%) are known
risk factors of subsequent injuries (2.0-7.6 times higher)34. The less time between
a previous injury and the current injury, and the shorter the follow-up period
between baseline and injury, the higher the risk of a new injury21, 34, 42.
Alignment lower extremity

Runners who have a variety of biomechanical variations in terms of alignment of
the lower extremities are more vulnerable to injury. Genu varum, genu valgum,
tibial torsion, pes planovalgus and pes cavus are considered predisposing
factors11, 13. A gait cycle can be divided into the support phase and the forward
recovery phase. Figure 1 describes the support phase by showing foot descent,
heel strike, midstance and toe-off.
17
Figure 1: Support phase in walking.
The foot prepares for descent by assuming a supine position. Following heel
strike the foot pronates which reaches a maximum in midstance. During this
phase, the foot absorbs much of the shock energy of landing. Resupination
starts in midstance. The foot becomes a rigid handle by locking the mid-tarsal
joint facilitating the toe-off phase. Supination involves a complex movement of
the ankle, subtalar and mid-tarsal joints, which is composed of plantar flexion,
inversion and adduction. Pronation is composed of dorsiflexion, eversion and
abduction.
A pes plano-valgus is often combined with a forefoot varus in the neutral position,
but when compensated during weight bearing, it will appear as a rearfoot valgus
and a ‘low arch’. The cavus foot will show a forefoot valgus when unloaded, but,
when compensated during weight bearing, it will appear as a rearfoot varus
and a ‘high arch’. A cavus foot will have a more lateral heel strike which results
in a longer pronation- distance in the midstance phase, in which the Achilles
tendon has to make a an elongated medial swing, therefore absorbing excessive
shock. A valgus foot causes eccentric pull on the Achilles tendon because of
overpronation.
Terrain
Training on uneven grounds or unstable terrain, for example in adventure racing,
has been described as a predisposing factor10, 11, 16.
In a systematic review, the incidence and determinants of lower extremity
running injuries in long distance runners were studied. There was limited
evidence for an association between female runners running on concrete
surfaces and lower extremity injuries34, 42. There was no significant association
between male runners, running on a specific surface and lower extremity injuries
and between training on hilly terrain, or running in the dark or in the morning
and these injuries, implying that there is no association between these factors
and lower extremity running injuries34, 42.
Temperature
One report among recruits mentioned a significant increase in risk of sustaining
‘peritendinitis’ when training outdoors in cold weather, with an incidence of
16
9.4 % in winter and 3.6 % in summer38. We could not find any further scientific
evidence on parallels with the aetiology of Achilles tendinopathy.
Prevention
In a prospective study in players at professional football clubs, a general lack of

awareness concerning of the benefits of injury prevention strategies as shown1,
19
. Because the exact aetiology of chronic Achilles tendinopathy is unknown, it
evidently is difficult to give strong advice for prevention. Some recommendations
have been made in the past. These measures for prevention mostly assess 5 major
etiologic factors, namely training methods, training surfaces, muscle dysfunction
and inflexibility, shoe-wear design and biomechanics11.
Training methods
Inexperienced runners are advised to keep to a speed that is gentle enough to
carry on a conversation with a running partner with no sense of breathlessness
(20-40 minutes). Training on alternate days is recommended. As physiological
adaptations occur, the intensity of running automatically increases without
awareness10, 11. Ideally, each individual should train with an individualized
program, avoiding any temptation to run at a rate better suited for the stronger
athlete.
Training surfaces
Training on uneven terrain or sudden transition, for example, from grass to
concrete or soft muddy trails at the same training volume may predispose to
injury. Consequently it is recommended to gradually convert to a different
training surface and shortly lower training intensity11, 14. Johnston and co-
workers recommended to increase the time spent on any new training surface
by no more than 10% weekly26.
Muscle dysfunction and inflexibility

Overuse injury leads to pain and limitation of movement, causing disuse
hypotrophy and muscle weakness. When continuing to exercise in exactly
the same manner, pain becomes more frequent and severe, causing more
limitation and weakness resulting in a cycle of reinforcement9. This problem can
be prevented by strength increasing and flexibility exercises at the first sign of
overuse. For example, running strengthens the hamstring and gastrocnemius
muscles, which subsequently need stretching. The quadriceps and anterior tibial
muscle groups are not stimulated as much, and consequently require additional
strengthening exercises to preserve muscle balance11.
The importance of strength and flexibility training for the calf muscles is stressed
by most authors13, 14, 20, 28, 31, 38, 40. Interestingly, there is no experimental evidence
to demonstrate that stretching before or after playing sports reduces the risk of
overuse injuries4, 17, 22, 43.
17
Shoe-wear
Current shoe technology has made an important contribution to the prevention
of injuries. The mid-sole is believed to provide shock absorption and flexibility,
where the Achilles tendon can be protected by an adequate heel wedge of 12-
15 mm and a solid heel counter to stabilize the calcaneus11, 14. In running, shoes
should match the runner’s feet and be replaced after 500 to 700 km because they
lose their shock-absorbing abilities9, 26.
Biomechanics
Disturbed biomechanics by deformities such as varus- and valgus feet may play a
major part in the development of chronic Achilles tendon problems. For control
of excess pronation, functional soft and semi-rigid orthotics can be custom-
made to prevent increased rotational forces in the foot and lower extremity41.
Conclusion
Achilles tendinopathy is common in sports active individuals, especially in

runners and badminton players. Overuse is thought to be the major cause of
this problem, the prevalence of which is increasing because of the current keep-
fit culture and the high-demands which athletes impose on themselves. Since
increasing scientific evidence has been published over the last 3 decades, advice
for prevention of injuries can be specified. This includes adaptation of training
methods and optimizing muscle strength, flexibility, and shoe-wear. Further
research will have to determine the exact aetiology of Achilles tendinopathy to
be able to optimize treatment and prevention.
Acknowledgement
The financial support of the Stichting Amphoraest (Foundation) is acknowledged.
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common problem in middle-aged competitive badminton players. Knee Surg Sports Traumatol
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18. Groenewegen R. Injury- and patient characteristics at the Sports Medical Advice Center. Thesis
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19. Hawkins RD, Fuller CW. A prospective epidemiological study of injuries in four English professional
football clubs. Br J Sports Med 1999;33:196-203.
20. Hess GP, Cappiello WL, Poole RM, Hunter SC. Prevention and treatment of overuse tendon injuries.
Sports Med 1989;8:371-84.
21. Hootman JM, Macera CA, Ainsworth BE, Martin M, Addy CL, Blair SN. Predictors of lower extremity
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30. Kujala UM, Sarna S, Kaprio J. Cumulative incidence of achilles tendon rupture and tendinopathy in
male former elite athletes. Clin J Sport Med 2005;15:133-5.
32. Linenger JM, Shwayhat AF. Epidemiology of podiatric injuries in US Marine recruits undergoing
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42. van Gent RN, Siem D, Van MM, van Os AG, Bierma-Zeinstra SM, Koes BW. Incidence and
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43. van MW. Can running injuries be effectively prevented? Sports Med 1995;19:161-5.
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Arch Intern Med 1989;149:2561-4.
16
Return to Sport
“Exercise to stimulate, not

annihilate.”
(Lee Haney)
Chapter 20.
Return to Sport
Karin G. Silbernagel, Kay Crossley, Jón Karlsson
Take Home Message
• Tendon injuries take a longer time to heal, compared to other tissues (e.g. muscle
and bone) injuries, even though the injury might not appear to be very severe
initially.
• For athletes with Achilles tendinopathy the aspects of the extent of tendon in
jury, the age of the athlete, the level of pain/symptoms, lower leg function
and the demands of the sport all need to be considered when estimating the
time for return to sports.
• In general athletes with Achilles tendinopathy can be expected to return to
sports anywhere from 6 weeks to one year. It is recommended, however, that the
athlete is not considered completely recovered until he/she has participated for
a full season and no longer has symptoms.
Achilles tendinopathy is a painful injury that affects the person’s ability to be

physically active27, 35. The main focus of treatment is usually to decrease the pain
and improve function such as walking and jogging30. For the athlete, however,
the main focus it to be able to return to sport. The average time to return to sport
is dependent on the extent of the injury, the sporting activity and the desired
level of sporting involvement. In this chapter, the various aspects that influence
17
the ability and the expected time for return to sport will be discussed along with
a proposal for a return to sport algorithm that will aid the clinician and athlete in
this difficult phase of recovery from Achilles tendinopathy.
1. Return to sports
Achilles tendinopathy is a condition renowned for its propensity for recurrence. It

is not unusual for patients with Achilles tendinopathy to have pain intermittently
for many years2, 4, 40. When physical activity is discontinued symptoms subside,
only to recur as soon as physical activity is resumed23. An athlete might initially
be able to continue with regular practice and competition, but as the injury
progresses it limits the athlete’s ability to participate in sport27. The excessive
loading of the Achilles tendon and training errors such as rapidly increasing
intensity and/or duration are reported to be present in 60-80% of patients with
Achilles tendinopathy16, 23. Haglund-Åkerlind and Eriksson14 also reported that
injured runners had not only run for more years but also covered longer distances
than the uninjured runners. Previous injury is also consistently identified as an
important risk factor for injury and athletes are especially at risk in the time
period just after return to sport33. Inadequate rehabilitation and returning
to sport prior to being fully recovered are risks that might be minimized with
appropriate guidance in the return to sport phase. Hägglund et al13 found a re-
injury rate of 44% in tendon injuries in soccer teams that had no assistance with
grading the return to full sports activity. However, in teams with a standardized
progression program that gradually increased loading during the return to sport
phase, there were no recurrences following tendon injuries13. This indicates that
at the latter stage of rehabilitation aiming for return to full sports participation
it is important to have a gradual and controlled progression giving the athlete
sufficient time to recover and evaluate symptoms. Since the athlete might not
have symptoms from the Achilles tendon during sports participation, players
may be tempted to return to sport prematurely. The evaluation of symptoms of
stiffness, pain and swelling after training, especially the following day is crucial
prior to determining the appropriate increase in intensity of training40, 42. A well-
designed and planned program for return to sport will help in the guidance in
achieving a balance between adequate and healthy loading and overloading of
the Achilles tendon.
2. Factors influencing return to sport
Various parameters need to be considered when planning return to sport after

Achilles tendinopathy. The most obvious aspect, which is also the one mostly
addressed in the literature, is the level of pain with physical activity30. Other
important aspects that need to be included in the decision making are the
healing and recovery of the tendon tissue18, 26, the regain of strength, range of
motion and function as well as the demands of the specific sport12, 41.
16
Return to Sport
2.1 Tendon tissue healing

Tendon tissue is described to pass through three different stages during the
healing process: the acute inflammatory, the proliferative and maturation, and
remodeling phase17, 18, 26. Even though the tendon has great potential to heal, it
is described that the last phase can continue for up to a year after injury17. Other
factors that can influence the rate of tendon tissue healing need to be considered
as well, when planning for return to sports. Tendon injury and healing appears
to be affected by age, hormonal levels, medications and genetics7, 17, 27, 32. Older
athletes might need to expect a longer time for recovery prior to returning to
sport compared to younger athletes. The tensile strength of healthy tendons is
described to reach a peak between 25-35 years of age, after which the tensile
strength slowly decreases17, 45. The use of anti-inflammatory medication has
also been reported to both promote repair as well as having a negative effect
on the healing process27. For an athlete with tendon injury such as Achilles
tendinopathy, this means that one could expect a healing/recovery period of
6-12 months. Conversely, mechanical loading, such as through exercise is crucial
for tendon healing during all stages of healing7, 21. During recovery from tendon
injury, it is therefore of great importance to ensure that loading is appropriate to
the capacity of the individual and the stage of tendon healing and the response
to loading monitored by subtle changes in symptoms, such as pain and stiffness
and function11, 40.
2.2 Tendon recovery

During running and jumping, the Achilles tendon is subjected to loads as high
as 6-12 times the body weight and if given adequate time and loading status,
the tendon will recover and strengthen22, 26. If the recovery time is inadequate,
cumulative trauma may lead to major injury such Achilles tendinopathy1, 26, 35.
There is a fine line between adequate and healthy loading and overloading of
the Achilles tendon. A study of collagen turnover, measured using microdialysis
in the peritendinous regions of the Achilles tendon, showed that an acute
bout of exercise increased the collagen synthesis of type I collagen 72 hours
after exercise25. Further studies by the same researchers on the synthesis and
degradation of collagen after a marathon run show that the synthesis of collagen
reaches a peak three days after the run and returns to normal levels again after
five days24. This indicates that the tendon responds to the loading and that the
response might take up to 3 days suggesting that athletes should plan for 2-3
days of recovery between heavy Achilles tendon loading activities. The theory
is that, by using recovery days between heavy tendon loading activities, the
tendon is given adequate time for its reparative efforts1, 26. In the clinic, we
recommend three recovery days between heavy tendon loading activities
while increasing the training level. At the latter stages, the amount of recovery
days can be decreased. Furthermore, the tendon does not only need to recover
from the injury but the forced decrease in activity might also have affected the
tendon’s loading capacity, which needs to be regained during the latter stages
of rehabilitation.
17
2.3 Pain and Symptoms

As described earlier, the most common symptoms of Achilles tendinopathy are
pain and stiffness18. Several studies have shown that allowing the patient to
experience pain during the rehabilitation has no negative effect on treatment4,
42
. Allowing for pain might even be of importance otherwise the load of the
Achilles tendon may not be sufficient to cause meaningful adaptive changes
in the tendon2. As described in the chapter on exercise as treatment, a pain-
monitoring model (figure 1) can be used to grade the level of pain and symptoms
allowed during rehabilitation42. In a study, the same pain-monitoring model was
used to allow for continued sports activity during rehabilitation40. In this study,
no negative effects could be demonstrated from continuing activities such as
running and jumping as long as the activity did not cause pain above 5 out of 10
on the visual analog scale and using recovery days between the activities. This
indicates that an athlete may not completely have to stop his/her athletic activity
and graded return to sports activity can be started prior to complete absence of
symptoms. This might also hinder total deconditioning of the athlete in regards
to his/her sport. Visnes et al.46 also allowed continued physical activity during
treatment in athletes with patellar tendinopathy. They could not, however,
show any positive effect of eccentric training when elite volleyball players with
patellar tendinopathy continued their normal in season training. No physical
activity monitoring model, such as the pain monitoring model, or incorporation
of recovery days was, however, used by Visnes et al.46, and this might explain the
lack of improvement. During the latter stage of recovery from tendon injury,
symptoms might be absent during the activity, however the following day the
athlete may notice increased pain and/or stiffness1,26. Therefore, not until the
day after the sports activity can it be determined whether the intensity level was
appropriate. In the clinic, the use of a training diary where the athlete document
the pain level during the activity as well as the next day (especially morning
stiffness) is of great use both for the athlete and the clinician.
Pain Monitoring Model
Visual Analog Scale - VAS
Acceptable Zone High Risk Zone
0 5 10
No pain Worst pain
imaginable
1. The pain was allowed to reach 5 on the VAS during the exercises
2. The pain after the whole exercise programme was allowed to reach 5 on the
VAS but should have subsided the following morning.
3. Pain and stiffness in the Achilles tendon was not allowed to increase from
week to week.
Figure 1: Pain-monitoring model.
16
Return to Sport
2.4 Physical parameters

Achilles tendinopathy causes pain and symptoms in patients and also
impairments in lower leg functions, such as decreases in strength, endurance
and plyometric ability5, 31, 34, 39. Risk factors for developing Achilles tendinopathy
include calf muscle weakness and/or muscle imbalance and altered joint
mobility of the foot and ankle complex20, 31. Addressing these factors with the aim
to regain full capacity is important for athletes prior to full sports participation12.
It has also been found that full symptomatic recovery does not ensure full
recovery of musculotendinous function of the lower leg in patients with Achilles
tendinopathy41. Therefore, athletes should be advised that even though the
symptoms have subsided, he/she might not have fully recovered from the injury.
Continued monitoring and evaluation of various physical parameters during the
rehabilitation and return to sports phase might prevent overtraining and guide
in how to design a maintenance program for that specific athlete. Functional
deficits might not only increase the risk of re-injury but also put the athlete at risk
for other injuries33. Rehabilitating the injury and addressing functional deficits
and possible risk factors are important during the return to sports phase, and
a maintenance program is recommended to be continued for at least a whole
season10, 43.
2.5 The load of the activity

Since there appears to be a consensus in the literature that return to full sport
activity should involve a gradual progression of the loading, it is of great
importance to have knowledge of the rate and magnitudes of Achilles tendon
load during various activities. At low rates of loading, tendons are more viscous
or ductile17. Tendons therefore absorb more energy at low rates of loading
compared to high rates. At high rates of loading, tendons become more brittle
and absorb less energy but they are then more effective in moving high loads17.
The load of the tendon can be increased in two ways when prescribing exercise,
either by increasing the external load or by increasing the speed of movement19.
In vivo measurements of the Achilles tendon has been performed by Komi et
al.22. They found that cycling produced an Achilles tendon force of less then 1kN,
walking a force of 2.6 kN whereas running produced a force of 9kN corresponding
to approximately 12 times the body weight. However, this study was conducted
on few participants and that the tendon forces are likely to vary considerably
between individuals22. Activities such as slower walking are associated with less
force then faster walking and a slower running pace produces less force then a
faster running pace on the Achilles tendon. Furthermore, running with a heel
strike gait pattern is considered to load the Achilles tendon less than running
with a forefoot strike gait pattern22. Komi et al22 also measured the load on the
Achilles tendon during a counter-movement jump (CMJ), a squat jump (SJ),
and hopping. During a CMJ, the person starts in an erect position, quickly bend
down and the perform a maximal vertical jump. In the SJ, the person starts in the
squatting position, and hopping is a submaximal jump like jumping rope. The
forces measured were CMJ 1.9 kN, SJ 2.2 kN and hopping 4.0 kN (approximately 5
times body weight)22. Also, by decreasing the contact times during hopping, the
17
rate of loading of the Achilles tendon is increased.

The above information can be used when designing a gradual loading return to
sports plan for an athlete. However, since the loading response of the tendon
varies between individuals we also believe that it is important to add the athlete’s
rating of perceived exertion of the activity on the Achilles tendon (by using the
Borg scale8) into the equation.
3. Time to return to sports
3.1 Recommendations for returning to sports activity

Early in the rehabilitation, rest from Achilles tendon loading activities is generally
recommended3, 35, 37. At the next stage of the rehabilitation, activities such as
deep water running and biking are suggested as a complement to treatment.
Resumption of activities such as running and jumping is generally recommended
when the symptoms have subsided. Often research studies have an intervention
for a minimum of 12 weeks, and then report that return to sports is allowed. In
studies on surgical treatment for Achilles tendinopathy more specific guidelines
can be found, with return to sports generally recommended between week
12-24 after surgery5, 28. However, complete rest may have a negative impact on
the athlete’s general capacity both in regards to cardiovascular ability as well
as muscular strength and the tendon’s capacity. In one study where running
and jumping was allowed during the initial stages of rehabilitation compared
to complete rest, they could not find any negative effect on outcome with
continued activity40. However, the level of the activity was graded based on the
above mentioned pain-monitoring model40. A complete rest might therefore not
be necessary, and allowing monitored sporting activity early in the rehabilitation
might also improve compliance and the athletes overall health and condition.
3.2 Reported times for return to sport

In the systematic review on non-operative treatment for midportion Achilles
tendinopathy, Magnussen et al30 identified four randomized treatment studies
that had return to sport or return to previous activity level as an outcome. After
12 weeks of treatment, a range from 10-86% of the subjects are reported to
return to sport in the various studies9, 29, 38. At one year follow-up, 55-90% of the
subjects are reportedly back to sport9, 42. After surgery for Achilles tendinopathy,
it is reported that 50-80% of the patients return to their previous sport and level
of activity36, 44. If the subjects in the above mentioned studies return to sports
completely asymptomatic or with symptoms is however not reported.
In summary, tendon injuries take a longer time to heal, compared to other tissues
(eg muscle and bone) injuries, even though the injury might not appear to be
very severe initially6, 17. For athletes with Achilles tendinopathy the aspects of
the extent of tendon injury, the age of the athlete, the level of pain/symptoms,
the lower leg function and the demands of the sport all need to be considered
when estimating the time for return to sports. In general athletes with Achilles
tendinopathy can be expected to return to sports anywhere from 6 weeks to one
16
Return to Sport
year. It is recommended, however, that the athlete is not considered completely

recovered until he/she has participated for a full season and no longer has
symptoms.
4. A Return to Sport algorithm following Achilles tendinopathy
The return to sport phase is a balancing act between a swift return to full activity
and avoiding overloading and re-injury of the tendon. A gradual progression into
the specific sport activity is always recommended in the literature regardless of
injury10, 13, 15. To be successful in guiding the athlete in the return to sports phase
after Achilles tendinopathy we recommend an algorithm where the load of the
activity, the athletes perceived exertion with the activity, the symptoms and pain
level, and recovery days are all incorporated in the decision making.
Step one is to, for each athlete, find specific activities that meet the requirement
for each level (light, medium and high) based on pain level and perceived
exertion8. Here the clinician’s knowledge on how to progress the load on the
Achilles tendon is of great importance along with an understanding of the
athletes sport. In table 1, the requirement for each activity level is found along
with an example of activities from a long distance runner.
Classification Pain level Pain level Athletes perceived Recovery days The individual
of activities during after activity exertion (in regards to needed athletes activity
activity (next day) the Achilles tendon) between
VAS VAS Borg Scale8 activities
Light 1-2 1-2 6-10 0 days (can be Walking fast

performed daily) for 70 min
Medium 2-3 3-4 11-14 2 days Jogging on flat

surface for
40 minutes
High 4-5 5-6 15-18 3 days Running 90%

of desired
speed for
30 minutes
Table 1: Classification scheme of activities during return to sports (with example for
a long distance runner).
Several activities can be added for each activity level. A specific training schedule
for approximately two to three weeks is then planned for the athlete. Light level
activity can be performed daily. After medium level activity, 2 days of recovery are
needed during which the athlete can not perform activity of the same or higher
level. High level activities need 3 days of recovery from medium and/or high
level activities. When the athlete improves (i.e. the pain level and the perceived
exertion level decreases), a new classification is performed. This usually is done
every 2-3 weeks. A previous medium level activity might then become light and
a new activity can be added on the high list. In table 2 is an example of a schedule
17
for the same long distance runner used in table 1. The athlete will then document
daily the pain and symptoms and also grade the perceived exertion after each
activity. The pain and perceived exertion should agree with the guidelines in the
classification scheme otherwise an adjustment of the activity needs to be made.
Day Activity Symptoms/Perceived Exertion

documented by the athlete
1 Running 90% for 30 min + Rehabilitation exercises
2 Walking 70 min + Rehabilitation exercises
5 Jogging 40 min + Rehabilitation exercises
16 Jogging 40 min + Rehabilitation exercises
Table 2: A 2-3 week return to sport plan for a long distance runner.
The proposed return to sport algorithm has been developed based on the
knowledge gained in the randomized study where some patients were allowed
to continue tendon loading activity during the rehabilitation when using the
pain-monitoring model40. In the clinic, the return to sports algorithm has been
used for both recreational and elite athletes. The advantage is to have a well
structured plan with gradual progression of loading the Achilles tendon and
gradual return to sports. Often the athlete’s coach or strength and conditioning
coach is involved when classifying activities. Further studies need to be
performed on the effectiveness of the return to sports algorithm.
16
Return to Sport
Conclusion
The aim of the proposed algorithm is to minimize the chance of recurrence of

symptoms and to facilitate the decision making in how to progress the sports
participation in athletes with Achilles tendinopathy. The program should be
modified to meet the specific needs of each individual athlete.
A comprehensive return to sports program should consist of;
• A proper maintenance rehabilitation program aimed at maintaining healthy
tendon tissue and minimizing deficits in strength, range of motion, balance and
function
• Addressing possible risk factors such as malalignment and sports equipment
• Gradual return to sports using the above return to sports algorithm.
All three parts are of utmost importance when returning athletes to competition
as quickly and safely as possible, with the goal of being able to participate in
sports for many years, not just to achieve short term participation.
References
1. Abate M, Gravare-Silbernagel K, Siljeholm C, Di Iorio A, De Amicis D, Salini V, et al. Pathogenesis of

tendinopathies: inflammation or degeneration? Arthritis Res Ther. 2009;11:235.
Clin Sports Med. 2003;22:727-41.
3. Alfredson H, Cook J. A treatment algorithm for managing Achilles tendinopathy: new treatment
options. Br J Sports Med. 2007;41:211-6.
6. Askling C, Saartok T, Thorstensson A. Type of acute hamstring strain affects flexibility, strength, and
time to return to pre-injury level. Br J Sports Med. 2006;40:40-4.
7. Aspenberg P. Stimulation of tendon repair: mechanical loading, GDFs and platelets. A mini-review.
Int Orthop. 2007;31:783-9.
8. Borg G. Borg’s perceived exertion and pain scales. Champaign, Ill. ;Leeds: Human Kinetics 1998.
9. Brown R, Orchard J, Kinchington M, Hooper A, Nalder G. Aprotinin in the management of Achilles
tendinopathy: a randomised controlled trial. Br J Sports Med. 2006;40:275-9.
10. Brukner PDRCOG, Khan K. Clinical sports medicine. 3rd ed. ed. Sydney ;London: McGraw-Hill 2007.
11. Cook JL, Purdam CR. Is tendon pathology a continuum? A pathology model to explain the clinical
presentation of load-induced tendinopathy. Br J Sports Med. 2009;43:409-16.
89.
13. Hagglund M, Walden M, Ekstrand J. Lower reinjury rate with a coach-controlled rehabilitation
program in amateur male soccer: a randomized controlled trial. Am J Sports Med. 2007;35:1433-42.
15. Humble RN, Nugent LL. Achilles’ tendonitis. An overview and reconditioning model. Clin Podiatr
Med Surg. 2001;18:233-54.
Foot Ankle Clin. 2005;10:255-66.
17. Jozsa L, Kannus P. Human tendons. Anatomy, physiology and pathology. Champaign: Human
Kinetics 1997.
19. Kannus P. Etiology and pathophysiology of chronic tendon disorders in sports. Scand J Med Sci
17
Sports. 1997;7:78-85.
20. Kaufman KR, Brodine SK, Shaffer RA, Johnson CW, Cullison TR. The effect of foot structure and
range of motion on musculoskeletal overuse injuries. Am J Sports Med. 1999;27:585-93.
22. Komi PV, Fukashiro S, Jarvinen M. Biomechanical loading of Achilles tendon during normal
locomotion. Clin Sports Med. 1992l;11:521-31.
23. Kvist M. Achilles tendon injuries in athletes. Sports Med. 1994;18:173-201.
24. Langberg H, Skovgaard D, Asp S, Kjaer M. Time pattern of exercise-induced changes in type I
collagen turnover after prolonged endurance exercise in humans. Calcif Tissue Int. 2000;67:41-4.
25. Langberg H, Skovgaard D, Petersen LJ, Bulow J, Kjaer M. Type I collagen synthesis and degradation
in peritendinous tissue after exercise determined by microdialysis in humans. J Physiol. 1999;521 Pt
1:299-306.
26. Leadbetter WB. Cell-matrix response in tendon injury. Clin Sports Med. 1992;11:533-78.
27. Longo UG, Ronga M, Maffulli N. Achilles tendinopathy. Sports Med Arthrosc. 2009;17:112-26.
28. Maffulli N, Testa V, Capasso G, Oliva F, Panni AS, Longo UG, et al. Surgery for chronic Achilles
tendinopathy produces worse results in women. Disabil Rehabil. 2008;30:1714-20.
tendinopathy: a systematic review. Clin J Sport Med. 2009;19:54-64.
Development of Achilles Tendon Overuse Injury: A Prospective Study. Am J Sports Med. 2006;34:226-
35.
32. Mokone GG, Schwellnus MP, Noakes TD, Collins M. The COL5A1 gene and Achilles tendon
pathology. Scand J Med Sci Sports. 2006;16:19-26.
33. Murphy DF, Connolly DA, Beynnon BD. Risk factors for lower extremity injury: a review of the
literature. Br J Sports Med. 2003;37:13-29.
Surg Am. 2002;84-A:2062-76.
37. Rompe JD, Furia JP, Maffulli N. Mid-portion Achilles tendinopathy--current options for treatment.
Disabil Rehabil. 2008;30:1666-76.
38. Roos EM, Engstrom M, Lagerquist A, Soderberg B. Clinical improvement after 6 weeks of eccentric
exercise in patients with mid-portion Achilles tendinopathy -- a randomized trial with 1-year follow-
up. Scand J Med Sci Sports. 2004;14:286-95.
2007;41:276-80.
42. Silbernagel KG, Thomee R, Thomee P, Karlsson J. Eccentric overload training for patients with
chronic Achilles tendon pain--a randomised controlled study with reliability testing of the evaluation
methods. Scand J Med Sci Sports. 2001;11:197-206.
44. Tallon C, Coleman BD, Khan KM, Maffulli N. Outcome of surgery for chronic Achilles tendinopathy.
A critical review. Am J Sports Med. 2001;29:315-20.
45. Tuite DJ, Renstrom PA, O’Brien M. The aging tendon. Scand J Med Sci Sports. 1997;7:72-7.
46. Visnes H, Hoksrud A, Cook J, Bahr R. No effect of eccentric training on jumper’s knee in volleyball
players during the competitive season: a randomized clinical trial. Clin J Sport Med. 2005;15:227-34.
16
Outcome Measures and Assessment Tools
“Everything that can be counted does not nec-

essarily count; everything that counts cannot
necessarily be counted”
(Albert Einstein)
Chapter 21.
Outcome measures and

Assessment Tools
Karin G. Silbernagel, Maayke N. van Sterkenburg, Annelie Brorsson,
Jón Karlsson
Take Home Message
• To evaluate outcome following treatment for Achilles tendinopathy it is

important to use reliable, valid and sensitive outcome measures.
• Evaluate patients’ pain and symptoms as well as lower leg function.
• Proper evaluations with validated tests are not only for scientific purposes, but
also of importance to the practitioner and the patient to follow the progress of
treatment and rehabilitation.
Achilles tendinopathy causes not only pain, symptoms and difficulty with
physical activity but also impairments in various aspects of lower leg function.
It is therefore important to continuously evaluate the patients’ progress with
both validated subjective scoring systems, such as the VISA-A questionnaire, and
with various validated functional tests. Also, the patients’ reported subjective
pain and ability to return to previous physical activity and sports are important
outcome measures. In this chapter, outcome measures for assessment of Achilles
tendinopathy are discussed.
17
Outcome measures – questionnaires
Many research studies have not used specific outcome measures validated for
Achilles tendinopathy. Instead, many studies use patient-reported pain (on a
Visual Analogue Scale), with tendon loading activity as a main outcome measure
to determine the success of treatment. Sometimes, investigators have graded
the success of treatment based on patient-reported improvements1, 26, 30, 34, 52.
To minimize response bias, which can affect the patients’ reports of pain and
symptoms, it is important to use outcome assessments in which the investigator
has a minimal influence on the scoring9, 51. In many of the above-mentioned
studies, it is difficult to judge how much the investigator could have influenced
the results. Many studies include questionnaires relating to symptoms, physical
activity, other treatments and previous injuries, but they are rarely specific
standardized questionnaires. The lack of standardized outcome measures for
Achilles tendinopathy caused previously difficulties when comparing treatment
studies51.
A performance test protocol and scoring scale for the evaluation of ankle injuries
by Kaikkonen and co-workers has been used in a follow-up study of patients
with Achilles tendinopathy17, 32, 33. It includes both objective and subjective
measurements, and has been shown to have good reliability in healthy
individuals and to be able to distinguish patients with ankle ligament injury from
healthy individuals. However, its validity on patients with Achilles tendinopathy
has not been evaluated.
Stanish and co-workers49 designed a system for tendon symptom classification

(Table 1). This classification system has not been evaluated for reliability and
validity, but it has been used as an outcome measure after surgery in patients
with ‘achillodynia’ 38.
Level Description of Pain Level of Sports Performance
1 No pain Normal
2 Pain only with extreme exertion Normal
3 Pain with extreme exertion and 1 to 2 hours afterwards Normal or slightly decreased
4 Pain during and after vigorous activities Somewhat decreased
5 Pain during activity and forcing termination Markedly decreased
6 Pain during daily activities Unable to perform
Table 1: Classification system for the effect of pain on athletic performance (Stanish
et al. 2000).
16
The VISA-A questionnaire
In 2001, Robinson and co-workers37 developed a questionnaire as an index of

the clinical severity of Achilles tendinopathy, the Victorian Institute of Sports
Assessment – Achilles questionnaire (VISA-A). This questionnaire is based on a
similar questionnaire for patellar tendinopathy55, 56. The VISA-A questionnaire
is the first outcome measure designed specifically for Achilles tendinopathy. It
has also been evaluated and shown to have good reliability and validity23, 37, 48.
A factor analysis of the Swedish version of the VISA-A questionnaire (VISA-A-S)
revealed that the questionnaire evaluated the two factors pain/symptoms and
physical activity48. The VISA-A-S questionnaire also has been shown to have a
large effect size indicating that it is responsive to clinically relevant changes47.
The high responsiveness (as indicated by an effect size of 2.1) also indicates that
the VISA-A-S questionnaire can be useful as an outcome measure in scientific
studies.
When reviewing the literature, we found that the VISA-A questionnaire had been
used as an outcome measure in 19 studies on treatment for patients with Achilles
tendinopathy6-8, 11-13, 24, 25, 35, 36, 39-41, 44-47, 53, 54. Furthermore, the VISA-A questionnaire
had been translated to Italian and Swedish, and these versions were also shown
to be reliable and valid23, 48.
The VISA-A is a self-administered questionnaire and provides an index of the
clinical severity, which is easily followed over time, for patients with Achilles
tendinopathy. The score ranges between 0-100, and a lower score indicates worse
symptoms and greater limitation on physical activity. It can be used to compare
different populations with Achilles tendinopathy and to facilitate comparisons
between studies. In the clinic, the VISA-A questionnaire can be used to assess the
clinical severity of the patient’s symptoms and provide a guideline for treatment,
as well as for monitoring the effect of treatment. This score might be less valid for
sedentary persons suffering from Achilles tendinopathy.
The Foot and Ankle Outcome Score

The Foot and Ankle Outcome Score (FAOS) is a questionnaire that assesses
patients’ symptoms, function and foot- and ankle-related quality of life 42. The
FAOS content is based on the Knee injury and Osteoarthritis Outcome Score
(KOOS), and has been shown to have good content validity and reliability in
patients with ankle injury42. It has, however, not been validated for patients with
Achilles tendinopathy. When used as an outcome measure for patients with
Achilles tendinopathy, it has been shown to be responsive to changes over time
with treatment 42, 18, 43.
17
Functional assessment
Achilles tendinopathy appears to cause difficulties with physical activities in

the active population, but exactly how it affects the lower leg muscle-tendon
functions is not fully understood45. Muscular strength, power, muscular
endurance, flexibility and motor control are important in physical performance.
The improvements of these factors are therefore often prescribed in rehabilitation
and injury prevention programs for tendon injuries10, 49.
Strength
Strength measurements with dynamometry have been performed in patients
with Achilles tendinopathy, in both etiological and prospective treatment
studies1, 2, 16, 27, 30, 33, 52.
Isokinetic dynamometry has been used to test ankle plantarflexion and
dorsiflexion strength both concentrically and eccentrically at various angular
velocities such as 30o/s, 50o/s, 60o/s, 120o/s, 180o/s, and 225o/s1, 2, 16, 27, 30. Paavola
and co-workers33, on the other hand, measured the isometric strength of the
lower limb in an isometric leg press dynamometer. Testa and co-workers 52
measured maximum isometric muscle activation, as well as isometric muscular
endurance, in patients with Achilles tendinopathy.
The various body positions described in the literature and used in the clinical
setting to measure plantarflexion and dorsiflexion strength are supine with the
knee and hip extended, sitting with the hip in 100-110 degrees of flexion and the
knee in either 40 degrees or 90 degrees of flexion and a closed-chain position in
which the measurement pad was placed on the knee1, 2, 16, 27, 28, 30. The reliability of
isokinetic and isometric dynamometry is generally high, and the various testing
positions for plantarflexion and dorsiflexion have good test-retest reliability2, 28. A
test for measuring muscular strength and power of the ankle plantarflexion in a
regular weight-training machine has also been shown to be reliable and valid for
patients with Achilles tendinopathy45. In this test, muscle power development,
i.e. the ability to produce a high force quickly, was evaluated both concentrically
and eccentrically-concentrically. The reason for evaluating muscle power was
because power is considered to be more important for both sports performance
and injury protection, than the ability to produce a high force 21. Patients with
Achilles tendinopathy had a significant deficit on their injured side (or most
symptomatic side) compared with their uninjured (or least symptomatic side) in
both concentric and eccentric-concentric plantarflexion while standing45.
It is, however, important to remember that strength tests are valid for measuring
improvements in strength, but they are only moderately correlated to functional
performance and need to be complemented with other types of functional
assessment3.
16
Endurance test
Muscular endurance testing is another type of muscle function measurement.
In a heel-rise test (also called heel-raise, heel-drop or toe-raise), repetitive
plantarflexion of the ankle is performed on standing until fatigued. It is the
most commonly used test for measuring the muscular endurance of the calf
musculature. The normal number of heel-rise repetitions on one healthy leg
is regarded to be approximately 25, but it can range from six to 70 in healthy
individuals22. The testing position for the subject is standing on one leg while
maintaining a straight knee, support with the fingertips for balance and avoiding
body sway forward. This test has been used in several research studies and has
shown good reliability (ICC 0.78-0.84)28, 50. The heel-rise test has been used
in evaluations of patients with Achilles tendon ruptures, as part of a scoring
scale used for patients with Achilles tendinopathy and in prospective studies
of Achilles tendinopathy29, 32, 33. Even though heel-rises are often prescribed
during the rehabilitation of Achilles tendinopathy, they are not commonly used
to evaluate the effect of treatment. One study found no significant deficit on
their injured side (or most symptomatic side) compared with their uninjured (or
least symptomatic side) on the toe-raise test45. Since the treatment for Achilles
tendinopathy include toe-raises, the test is useful to evaluate the effect of
treatment and improvements in heel-rise endurance with treatment has been
found in patients with Achilles tendinopathy46.
Jump tests
Various jump tests are often used to evaluate function in patients with lower
extremity injuries, as well as to evaluate functional performance in athletes14, 31,
57
. High loads occur on the Achilles tendon during activities during which the
so-called stretch-shortening cycle (SSC) is utilized15, 20. The SSC is a combination
of an eccentric muscle action (with lengthening of the muscle and tendon)
immediately followed by a concentric muscle action (shortening of the muscle-
tendon complex)5, 19. The concentric force production will be higher when
preceded by an eccentric muscle action compared with a pure concentric
muscle action5, 19. The efficiency of utilizing the SSC in various types of jumps
reportedly ranges from 17-34%4, 15. Achilles tendon’s elasticity is important to
store and release energy during the SSC, and thereby improves the economy
and performance of motion15, 19. Changes in lower leg functions such as muscle-
tendon strength, endurance, flexibility and motor control could all affect the
various mechanisms in the SSC, and these changes might be etiological factors
for the development of Achilles tendinopathy16, 50.
Jump tests such as counter-movement jumps (CMJ), squat jump (SJ) and hopping
have been used to evaluate the loading of the Achilles tendon 20. CMJ and SJ
are vertical jumps where the jump height is used for evaluation. In the CMJ, the
starting position is upright whereas for the SJ the starting position is with the
knees bent. Hopping is a continuous rhythmical jump, similar to jumping rope,
and here the contact times and flight times are usually evaluated 15, 20. A drop
counter-movement jump (Drop CMJ) is performed jumping down from a box/
17
step and directly on landing performing maximal vertical jump. This type of jump
is often used in training to improve jumping ability in athletes and it also places
high demands on the ability to utilize the SSC. One study on patients with Achilles
tendinopathy found significant deficit in hopping and Drop CMJ on their injured
side (or most symptomatic side) compared to their uninjured (or least symptomatic
side) but this was not found on the CMJ45, 46. Another often used jump test is the
one-legged hop for distance and it has also been used in a prospective study to
identify intrinsic risk factors for Achilles tendon overuse injury 27. Even though
Achilles tendinopathy is thought to be related to running and jumping, there
are only a few prospective treatment studies that have evaluated the patient’s
recovery in terms of jumping ability.
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17
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16
17
CURRENT CONCEPTS IN ORTHOPAEDICS
CURRENT CONCEPTS
This book on Achilles tendon ruptures is the first production of the Achilles Tendon
Study Group and is part of an upcoming current concepts series on Achilles tendon
problems. The best available evidence and expert opinion on the aetiology,
diagnosis and treatment of Achilles tendon ruptures was collected and discussed in
an international panel of expert orthopaedic surgeons. The outcome is brought
together in this manuscript.
The Achilles Tendon Study Group is accommodated by ESSKA as an affiliated society.

Since 1984 ESSKA is devoted to education, stimulating the further development of
research, and providing a forum for presentation and discussion of issues on
Arthroscopy, Orthopaedic Sports Medicine and Knee Surgery. If you are interested in
the activities of ESSKA or want to join the organisation as a member, you can find
further information on the ESSKA website: WWW.ESSKA.ORG.
This book is the first issue in the series "Current Concepts in Orthopaedics" published
by the new publishing house DJO publications, a division of DJO Incorporated. It is
the goal of DJO publications to bring experts together with a view to produce
top-quality publications on topics of current consensus (or controversy) and a global
approach to an orthopaedic or medical problem. DJO Incorporated has a mission to
improve lives by developing medical devices that become the standard of care in the
prevention, treatment and rehabilitation of musculoskeletal conditions. With DJO
Publications we intend to assist the medical professional to communicate their
views and knowledge on what they see as the current "Standard Approach" and
"Standard of Care" on different indications throughout the medical world.
For more information on this and future publications please contact us at:
info@DJOpublications.com
www.DJOpublications.com
ISBN number: 978-0-9558873-2-1
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CURRENT CONCEPTS IN ORTHOPAEDICS

Achilles Tendinopathy - CURRENT CONCEPTS

A DJO Incorporated initiative

First edition 2010

ISBN number: 978-0-9558873-2-1

© 2010 by DJO Publications

Published by DJO Publications

C. Niek van Dijk

Murat Bozkurt Kay Crossley

Annelie Brorsson Brian Donley

Mahmut N. Doral Jón Karlsson

Nicola Maffulli Paul T. Salo

Christopher J. Pearce Roland Thomée

C. Niek van Dijk

Maayke N. van Sterkenburg

It is acknowledged that some chapters are controversial as they report on treat-

“88.2% of all statistics are made up on

Take Home Message

runners without Achilles tendon pain11.

A retrospective study found various statistically significant correlations between

hormone replacement therapy also appear to have a higher incidence of Achilles

Tendinopathy of the Achilles tendon is common in athletes, and especially run-

“Achilles absent was Achilles still”

“A surgeon is worth an army

(Homer’s; The Iliad)

Take Home Message

The AT comprises bundles of collagen fibrils, each wrapped in endotenon, which

constant finding, it has an anterior bursal wall composed of fibrocartilage and a

We thank to N. Apaydın MD from Ankara University Department of Anatomy

“As your thoughts will steer you - I will be

Take Home Message

• Appropriate loading and adaptation increases cross-sectional area and tensile

Mechanobiology studies changes in tissue structure and function following

the concepts of mechanobiology, but mechanobiology shifts the emphasis from

effects of mobilization are associated with an increased expression of sensory

the Achilles tendon of human subjects exhibiting symptoms of tendinopathy

Neuronal Interactions in Tendinopathy

Several interesting abnormalities in the peripheral neuronal innervation have

Sensory Nerve Ingrowth

Increase in Sensory Neuropeptides

Immunohistochemical and semi-quantitative assessments have clearly

in tendinopathic patients, such as tenocyte metaplasia, hypercellularity, and

SP receptor neurokinin (NK)-1

Decreased Autonomic Innervation

Tendinopathic tendons exhibit a decreased occurrence of sympathetic nerve

Increased cellular autonomic mediator production as a response to

Compensatory up-regulation of cellular noradrenaline production has been

in human tendinopathy were immunohistochemically identified and most

Up-regulated Glutamate Receptor-ligand Pathways

Elevated interstitial levels of glutamate have also been found in tendinopathy by

tendon tendinosis - a pilot study. Life sciences 2007;30:80:2235-8.

phenotype and proliferation of intestinal fibroblasts. Am J Physiol Gastrointest Liver Physiol

“The journey is the reward”

Take Home Message

Biomechanics of the healthy Achilles tendon - Properties of the Achilles

Functional muscle-tendon unit (MTU)

Visco-elastic / spring-alike properties

Figure 1: Spring-versus-catapult properties.