Injury, Int. J.

Care Injured 47S6 (2016) S68–S76

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Injury
j o u r n a l h o m e p a g e : w w w. e l s e v i e r . c o m / l o c at e / I n j u r y

Masquelet technique: myth or reality? A systematic review and meta-analysis

Ilaria Morellia,b, *, Lorenzo Dragoc, David A. Georged, Enrico Gallazzia,b, Sara Scarponia, Carlo L. Romanòa,b
a
Department of Reconstructive Surgery and Osteo-articular Infections C.R.I.O. Unit, I.R.C.C.S. Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy
b
Università degli Studi di Milano, via Festa del Perdono 7, 20122 Milano, Italy
c
Laboratory of Clinical Chemistry and Microbiology, I.R.C.C.S. Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy
d
Department of Trauma and Orthopaedics, University College London Hospitals, London, UK

K E Y W O R D S A B S T R A C T

Masquelet technique Introduction: The induced membrane technique (IMT) or Masquelet technique, is a two-step surgical procedure
induced membrane technique used to treat pseudoarthroses and bony defects. Many authors have introduced variants to the technique. This
systematic review study aims to compare the surgical variants of IMT and to evaluate its efficacy in achieving infection eradication
meta-analysis and bone union.
bone non-union treatment Methods: A systematic review was carried out following the PRISMA guidelines. PubMed and other medical
osteomyelitis
databases were explored using keywords “Masquelet technique” and “induced membrane technique”. Articles
bone defect
were included if written in English, French or Italian, dealing with IMTemployed to long bones in adults, reporting
at least 5 cases with a 12 months-mean follow-up. Patients’ clinical features, bone defect features, aetiologies,
surgical data, complications, reinterventions, union rates and infection eradication rates were searched. Fischer’s
exact test, chi-square test and unpaired t-test were used for the statistical analysis on the individual patient’s data.
Results: Seventeen papers met the inclusion criteria (427 patients). Among these, only 10 studies reported
individual patient’s data (137 cases). The union rate was 89.7% and the infections rectified in 91.1% of cases. The
bone defect length ranged from 0.6 to 26 cm. The main complications were superficial (21; 4.9%) and deep surgical
site infections (19; 4.4%), failure of one of the IMT steps ( persistence of infections or non unions, 77, 18%), with
subsequent requirement for further surgery. The surgical variants included the use of antibiotic-coated spacers,
internal fixation during the first step, use of Reamer-Irrigator-Aspirator technique, iliac crest grafting, bone
substitutes and growth factors. However, univariate analysis only showed a positive correlation of the need for re-
interventions with poorer bone union rates ( p = 0.005) and complications ( p < 0.001), while patients undergoing
IMT because of bone infections had a higher risk of surgical complications ( p < 0.001).
Discussion: IMT aims to achieve bone union and infection eradication, but persistence of infection or non-union
was noted in 18% of cases necessitating re-interventions. This may be related to the different anatomical sites that
the technique has been applied and different local and patient related conditions. We believe the choice of a
surgical technique to achieve union should be tailored to the individual patient’s needs. This systematic review
was limited by the few studies meeting our inclusion criteria, and their high variability in data reporting, making it
impossible to undertake a meta-analysis.
Conclusion: Further studies are needed to demonstrate the role the patients’ clinical features and IMT variants have
upon achieving bone union and infection eradication.
© 2016 Elsevier Ltd. All rights reserved.

Introduction
The induced membrane technique (IMT) firstly described by
Masquelet et al. is a two-step procedure to treat bone defects and
non-unions [1]. Masquelet describes an initial debridement of soft
* Corresponding author at: Dr. Ilaria Morelli Department of Reconstructive Surgery and
Osteo-articular Infections C.R.I.O. Unit, I.R.C.C.S. Galeazzi Orthopaedic Institute, Via R.
Galeazzi 4, 20161, Milan, Italy. Phone/Fax: +393331266580.
E-mail address: ilaria.morelli90@gmail.com (Ilaria Morelli).
tissues and necrotic bone to bleeding healthy tissue (“paprika sign”),
and the use of a polymethyl methacrylate (PMMA) cement spacer
placed in the bony defect, which is stabilised with a temporary external
fixator [2,3]. During the initial stage, soft tissue reconstruction is
required if coverage is inadequate [1–8].
The role of the spacer is two-fold; it prevents fibrous tissue invasion
of the defect area, whilst inducing the development of a surrounding
pseudo-synovial membrane, as a result of a foreign body reaction [9].
After 6–8 weeks, the second step is undertaken. The induced
membrane is carefully incised and the spacer removed. Morcellized

0020-1383 / © 2016 Elsevier Ltd. All rights reserved.

 I. Morelli et al. / Injury, Int. J. Care Injured 47S6 (2016) S68–S76
cancellous bone from the iliac crest is implanted and the membrane
closed with definitive fixation [1].
The membrane is key to provide a vascular source to the bone graft
[10] and also secretes growth factors (such as BMP-2, VEGF and
TGF-beta1) [9]. The autologous bone graft is then able to allow
osteoconduction (acting as a scaffold), osteoinduction and osteogen-
esis (containing further growth factors and osteoprogenitor cells) [11].
Several small case series reports have demonstrated the efficiency of
IMT, particularly in post-traumatic defects, septic and aseptic non-
unions, tumor resections, and irradiated bones.
The original technique has been modified in a variety of ways and
includes the use of antibiotic-coated or impregnated spacers (used in
septic pseudoarthroses and infected bone resections) [2,4,5,7,8,12–15],
internal and/or definitive fixation during the first stage [1,3–8,16–19]
and utilisation of spongy autograft obtained through the Reamer-
Irrigator-Aspirator (RIA) technique [4–7,12]. Hydroxyapatite and
tricalcium phosphate bone substitutes, as well as demineralized
bone matrix (DBM) and demineralized bovine bone (DBB) have been
added to the graft to increase graft volume [1,2,6,7,12,20]. The addition
of growth factors, such as BMP-7, has been used to improve
osteoinductivity [3–7,10,12,13], and non-vascularized or vascularized
bone grafts can provide additional structural support [1,3,6–8].
Fig. 1. PRISMA IPD flow diagram.
S69
In spite of these modifications, a systematic review evaluating the
impact of these on the efficacy of the Masquelet technique, is still
absent in the medical literature. Therefore, in this systematic review we
aim to evaluate the impact of these variants on the efficacy of IMT,
specifically comparing infection eradication and union rates for long
bones defects and non-union in adults.
Methods
In agreement with the Preferred Reported Items for Systematic
Reviews and Meta-Analyses Statement for Individual Patient Data
(PRISMA-IPD), a systematic review of the medical literature was carried
out. PubMed, Scopus, Ovid, Embase, Science Direct, Web of Science
databases were searched using the keywords “Masquelet technique”
and “induced membrane technique,” from 2000 until the end of July
2016 (Figure 1). Original articles written in English, French, or Italian
reporting more than 5 cases of IMT employed for long bones in adult
patients (≥15 years old), with a mean follow up of 12 months were
included. After excluding the duplicates, two independent reviewers
(IM, EG) screened the identified articles for inclusions following the
review of the abstracts. In case of disagreement, uncertain articles had
been read in full to assess their relevance to the study. The selected
S70 I. Morelli et al. / Injury, Int. J. Care Injured 47S6 (2016) S68–S76

papers then underwent a full-text analysis before deeming if
appropriate for inclusion in the systematic review and meta-analysis.
Specific information was obtained from the included studies, such
as the patients’ demographics (age, gender), comorbidities (diabetes,
rheumatoid arthritis, BMI, cigarette smoking, chronic use of steroids,
NSAIDs, bisphosphonates), aetiology, history of previous surgery before
index procedure, and duration from the trigger event to IMT surgery.
We classified the bone involvement (tibia, fibula, femur, humerus,
radius, ulna, clavicle), defect size (cm), shape (conical/non segmental,
cylindrical/segmental), and site (diaphysis, metaphysis) [3,21].
Regarding the surgical procedure we determined the variation of
the techniques used during the first and second stage, which included
various spacer types, fixation techniques ( plate, nail, plate and nail,
antibiotic-coated nail, wires, external fixator), bone graft use (RIA, iliac
crest, allografts, bone substitutes, demineralized bone matrix/bovine
bone, growth factors, vascularized or non-vascularized fibular auto-
graft), use of systemic antibiotics, need for soft tissue reconstruction,
duration between stages, and rehabilitation regime.
The main outcome measures were progression to bone union
and infection eradication. Complications included failure of either the
first or second stage (resulting in definitive or temporary non-union
until a second union surgery was performed), material failure (e.g.
breaking of an intramedullary nail), re-fractures, decreased range of
motion, superficial and deep infections, disorders in wound and soft
tissues healing. The need for repeated interventions, amputations and
additional union procedures were also assessed.
Data was analyzed using SPSS statistics software (version 21, 2013,
IBM Corporation, New York, USA). A descriptive statistical analysis
was carried out on the aggregate data. Univariate analysis was
undertaken to determine risk of non-union and failure to eradicate
infection using unpaired t-test, Fischer’s exact test and Chi square test
where applicable.
Results
Six hundred and twenty-eight papers were initially identified and
screened (Figure 1). After duplicates were excluded, 19 studies were
read in full to assess their relevance to this study. Seventeen studies [1–
8,12–20] reporting aggregate data met our inclusion criteria, with 427
patients undergoing IMT.
The mean age of included patients was 39.03 (range 15–84), and
included substantially more males (353, 82.7%), with a mean follow-up
of 15.75 months (range 6–264) (Table 1). The main reasons for
undergoing the procedure was grouped into discrete categories;
tumour, infection (included osteomyelitis and septic non-unions),
and post-traumatic defect (including fractures, where possible further
classified in cases undergoing surgery due to aseptic non-unions or
acute bone losses) (Table 2).
Bone defects primarily affected the tibia (287, 67.2%), followed by
fibula (55, 12.9%) and femur (83, 19.4%) (Table 3). The metaphysis was
involved in 62 (14.5%) defects, and were a combination of cylindrical
(116; 27.2%) and conical shapes (29; 6.8%) [3,5,8,15]. The mean size of
the defects was 5.53 cm, and classified according to Karger’s class: I
(<2 cm) in 15 defects, II (2–5 cm) in 99, III (5–10 cm) in 114 and IV
(>10 cm) in 61 [3] (Table 4). Further pre-operative information is
available in Table 5.
Following debridement during the first stage, antibiotics were
added to the spacer in the majority of patients (267, 62.5%), which was
most often combined with external fixation (152, 35.6%) and soft tissue
reconstruction (156, 36.5%) (Table 6). During the second stage,
definitive fixation was frequently undertaken with either a plate
(157; 36.8%), an intramedullary nail (117; 27.4%) or an external fixator
(121; 28.3%). In the 21% of cases, the fixation device was substituted
during the second stage (Table 7). The sources of bone graft were RIA
(from various sites) (137; 32.1%), and/or the iliac crest (300; 70.3%).
Allogenic graft was used in 58 patients (13.6%), and the addition of
growth factors was used in 128 patients (30%) (Table 8).
Complications were high (49.6%) amongst all studies, occurring
in 15% to 100% of patients (we often found more than a complication
per case) (Table 9). The main complications weresuperficial (21; 4.9%)
and deep surgical site infections (19; 4.4%), failure of one of the IMT
steps ( persistence of infections or non unions, 77, 18%), with
subsequent requirement for further union surgery or another kind of
intervention in 41 (9.6%) and 114 (26.7%) patients respectively (Table
10). However, at the last follow-up, infection was eradicated in 216
patients (91.1% of patients with an osteomyelitis), and 383 patients
(89.7%) went onto have union of the graft and resolution of the defect
with a time to union ranging from 6 to 211 weeks after the second stage
(Table 11).
Minimal information was available regarding individual patient
data in the included studies (137 patients). Based on the reported IPD,
we undertook a univariate analysis to determine the variables
associated to infection eradication, bone union, need for re-interven-
tions and presence of complications. Given the small numbers, only the
need of further union surgeries was significantly associated to poorer
bone union rates ( p = 0.005), while the need for re-interventions and

Table 1.
Patient demographics

Articles Sex Age

N°
PMID Cases Male (%) Female (%) Min Max Mean SD

Apard (2010) [2] 20605548 Retrospective 12 10 83.3 2 16.7 18 74 40.67 17.96

Azi (2016) [15] 27124824 Retrospective 33 26 78.8 7 21.2 18 54 33 –
Donegan (2011) [7] 22049954 Retrospective 11 8 72.7 3 27.3 15 84 45.45 19.26
El Alfy (2015) [19] 26806972 Prospective 17 15 88.2 2 11.8 26 58 43.12 8.28
Gupta (2016) [20] 27293290 Prospective 9 7 77.8 2 22.2 18 55 35.44 11.38
Karger (2012) [3] 22244249 Retrospective 84 79 94.0 5 6.0 4 77 32 –
Kawakami (2015) [8] 26377029 Retrospective 6 5 83.3 1 16.7 29 59 47.5 12.71
Luo (2016) [17] 27234664 Retrospective 7 3 42.9 4 57.1 23 74 47.1 –
Masquelet (2000) [1] 10929461 Retrospective 31 26 83.9 9 29.0 15 66 32 –
Moghaddam (2015) [12] 26542865 Prospective 50 42 84.0 8 16.0 15 72 47.8 13.8
Obert (2016) [16] Prospective 9 9 100.0 0 0.0 17 64 38.2 –
Olesen (2015) [14] 26747918 Retrospective 8 7 87.5 1 12.5 24 70 45.63 14.3
Scholz (2015) [13] 26542857 Retrospective 13 12 92.3 1 7.7 16 69 41.4 –
Stafford (2010) [5] 21144933 Retrospective 27 22 81.5 3 11.1 20 58 38.38 10.26
Taylor (2015) [4] 25875174 Retrospective 69 51 73.9 18 26.1 18 79 42.3 16.9
Wang (2016) [18] 27033845 Retrospective 32 22 68.8 10 31.3 19 72 40.03 15.14
Zappaterra (2011) [6] 21816650 Prospective 9 9 100.0 0 0.0 17 63 41.22 15.49
Weighted mean 39.03 –
Total 427 353 82.7 76 17.80 –

Legend: %=% of total patients for each study; SD=Standard deviation.

 I. Morelli et al. / Injury, Int. J. Care Injured 47S6 (2016) S68–S76 S71

Table 2.
Pre-operative diagnoses

Etiology
N°
Articles Cases Tumor (%) Post traumatic defect (%) Infection (%) Aseptic non union (%) Acute bone loss (%)

Apard 12 0 0.0 12 100 7 58.3 1 8.3 4 33.3

Azi 33 0 0 33 100 23 69.7 – – – –
Donegan 11 1 9.1 10 90.9 4 36.4 2 18.2 5 45.5
El Alfy 17 0 0 12 71 17 100.0 – – – –
Gupta 9 0 0 9 100 8 88.9 – – – –
Karger 84 0 0.0 84 100 41 48.8 0 0.0 84 100.0
Kawakami 6 0 0 5 83.3 6 100 0 0.0 1 16.7
Luo 7 0 0 7 100 7 100.0 – – – –
Masquelet 31 4 12.9 6 19.4 24 77.4 1 3.2 2 6.5
Moghaddam 50 0 0 50 100 35 70.0 15 30.0 0 0.0
Obert 9 0 0 9 100 0 0.0 – – – –
Olesen 8 0 0 8 100 3 37.5 – – – –
Scholz 13 0 0 8 61.5 13 100 – – – –
Stafford 27 0 0.0 27 100 7 25.9 – – – –
Taylor 69 0 0.0 69 100 7 10.1 0 0.0 69 100.0
Wang 32 0 0 32 100 32 100.0 – – – –
Zappaterra 9 2 22.2 7 77.8 3 33.3 2 22.2 2 22.2
Total 427 7 1.6 388 90.9 237 55.5 21 4.9 167 39.1

Legend: %=% of total patients for each study.

Table 3.
Surgical sites

Long bone involved

N°
Articles Cases Tibia (%) Fibula (%) Femur (%) Humerus (%) Radius (%) Ulna (%)

Apard 12 12 100.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0

Azi 33 19 57.6 0 0.0 15 45.5 0 0.0 0 0.0 0 0.0
Donegan 11 6 54.5 0 0.0 5 45.5 0 0.0 0 0.0 0 0.0
El Alfy 17 13 76.5 0 0.0 4 23.5 0 0.0 0 0.0 0 0.0
Gupta 9 9 100.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0
Karger 84 61 72.6 54 64.3 13 15.5 6 7.1 4 4.8 4 4.8
Kawakami 6 1 16.7 1 16.7 1 16.7 1 16.7 3 50.0 3 50.0
Luo 7 0 0.0 0 0.0 0 0.0 0 0.0 4 57.1 6 85.7
Masquelet 31 27 87.1 0 0.0 2 6.5 3 9.7 2 6.5 1 3.2
Moghaddam 50 50 100.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0
Obert 9 4 44.4 0 0.0 2 22.2 1 11.1 0 0.0 2 22.2
Olesen 8 6 75.0 0 0.0 2 25.0 0 0.0 0 0.0 0 0.0
Scholz 13 5 38.5 0 0.0 3 23.1 0 0.0 2 15.4 0 0.0
Stafford 27 19 70.4 0 0.0 8 29.6 0 0.0 0 0.0 0 0.0
Taylor 69 35 50.7 0 0.0 16 23.2 6 8.7 6 8.7 1 1.4
Wang 32 20 62.5 0 0.0 12 37.5 0 0.0 0 0.0 0 0.0
Zappaterra 9 0 0.0 0 0.0 0 0.0 6 66.7 2 22.2 1 11.1
Total 427 287 67.2 55 12.9 83 19.4 23 5.4 23 5.4 18 4.2 489
Total bones

Legend: %=% of total patients for each study.

Table 4.
Bone defect characteristics

Bone defect class Bone defect length (cm) Metaphyseal involvement

N°
Articles Cases I (%) II (%) III (%) IV (%) Min Max Mean SD y (%) n (%)

Apard 12 0 0 1 8 8 67 3 25 5 15 8.67 3.06 0 0 12 100

Azi 33 1 3 8 24 23 70 2 6 1.8 15.5 6.7 – – – – –
Donegan 11 0 0 2 18 7 64 2 18 4 15 8.5 3.73 6 55 5 45
El Alfy 17 0 0 2 12 14 82 1 6 5 11 7.59 1.66 2 12 15 88
Gupta 9 0 0 7 78 2 22 0 0 3.3 8.5 5.26 1.57 0 0 9 100
Karger 84 6 7 29 35 26 31 23 27 – 23 6.8 3.1 0 0 84 100
Kawakami 6 0 0 4 67 2 33 0 0 3 8 4.83 1.97 – – – –
Luo 7 0 0 3 43 4 57 0 0 4 8 5.6 – 0 0 7 100
Masquelet 31 0 0 0 0 0 0 20 65 4 25 – 0 – – – –
Moghaddam 50 – – – – – – – – 0.6 26 4 4.3 29 58 21 42
Obert 9 – – – – – – – – 4 12 7.2 – 3 33 6 67
Olesen 8 0 0 4 50 4 50 0 0 2.9 9.3 5.49 2.3 – – – –
Scholz 13 0 0 0 0 11 85 2 15 5.5 14.5 8.08 0 0 0 13 100
Stafford 27 6 22.2 13 48.1 3 11.1 5 18.5 1 25 5.85 6.31 18 67 9 33
Taylor 69 – – – – – – – – 1.3 14 5 2.9 – – – –
Wang 32 2 6 21 66 6 19 3 9 1.5 12.5 5.05 3.18 – – – –
Zappaterra 9 0 0 5 56 4 44 0 0 2.5 8 5.28 1.89 4 44 5 56
Weighted Mean 5.53
Total 427 15 3.5 99 23.2 114 26.7 61 14.3 62 14.5 186 43.6

Legend: %=% of total patients for each study.

S72 I. Morelli et al. / Injury, Int. J. Care Injured 47S6 (2016) S68–S76

Table 5.
Pre-operative details

Systemic
Time from cause to non union surgery (weeks) Previous surgeries antibiotics
N°
Articles Cases Min Max Mean SD Min Max Mean SD yes no

Apard 12 0 24 10.17 8.14 – – – – 12 0

Azi 33 16.4 252.7 72.6 – 0 3 0.7 1 33 0
Donegan 11 – – – – – – – – – –
El Alfy 17 – – – – – – – – 17 0
Gupta 9 3.3 96 36.8 – 0 3 1.7 – 9 0
Karger 84 0 0 32 0 0 0 4.5 0 – –
Kawakami 6 12 96 31.33 32.54 1 5 2.33 1.37 – –
Luo 7 – – – – 1 3 1.57 – – –
Masquelet 31 – – – – – – – – 31 0
Moghaddam 50 12 220 92.8 52 1 31 6.7 6.8 – –
Obert 9 0 0.4 – – 0 0 0 0 – –
Olesen 8 – – – – – – – – – –
Scholz 13 – – – – 0 0 4.7 0 13 0
Stafford 27 – – – – 0 0 2.8 0 – –
Taylor 69 – – – – 1 7 1.6 1.4 6 1
Wang 32 12 960 76.8 – – – 3.7 – 32 0
Zappaterra 9 0 416 88 0 0 1 0.5 0 – –
Weighted Mean 31.88 2.68
Total 427 153 1

further union surgeries were significantly higher in patients with
complications ( p < 0.001 and p = 0.001, respectively). Finally, patients
undergoing IMT because of bone infections had a higher risk of surgical
complications ( p < 0.001). There was no difference in type of fixation
used or modes of bone grafting.
Discussion
Masquelet et al. first presented the induced membrane technique
in 1986, publishing a case series 14 years later [1]. The technique
underwent several changes, and has been employed in different
contexts and different methodology.
This is, to our knowledge the first systematic review aimed at
analysing the results of the application of the IMT in septic and aseptic
non-unions, osteomyelitis, traumatic bone losses and tumor resections
in adult patients.
The bone defects ranged from 0.6 to 26 cm [12]. Overall, the mean
union rate found in this systematic review was 89.7% and the rate of
infection eradication 91.1%, although 33 (7.7%) among these patients
needed an additional union procedure to heal. Therefore, the present
analysis confirms the ability of the IMT to achieve the two main goals
it is commonly used for, despite its application in very large bone
defects.
Comparing it to other bone reconstruction techniques effective for
defects over 20 cm, such as Ilizarov bone transport, IMT has the
advantage that the healing time is independent from the defect length
[22]. Avoiding the use of an external frame for prolonged periods of
time, IMT is generally better accepted and can be used in less compliant
patients [22]. Moreover, it does not require a microsurgical approach
but there is an option of utilizing vascularized fibular grafts for less
responsive bones (osteomyelitic or irradiated bones) [10,22]. To achieve
bone union in large segmental defects, bone substitutes as tricalcium
phosphate (not exceeding a 1:3 ratio) and BMP7 have been added to
the graft to improve its osteoconductivity and osteoinductivity [10,22].
However, IMT needs two invasive surgical procedures, which may
be deemed inappropriate and high-risk for elderly patients compared

Table 6.
Masquelet technique – First stage

Osteosynthesis 1
Spacer Spacer duration (weeks) stage

N° Antibiotic Plate+ Plast.

Articles Cases yes no AIS (%) type Min Max Mean SD Plate (%) Nail (%) Nail (%) Wires (%) EF (%) None (%) Proc. (%)

Apard 12 12 0 12 100 G 2 6 4 0 0 0 12 100 0 0 0 0 0 0 0 0 11 92

Azi 33 33 0 33 100 G+V 7 28 14 5.7 0 0 0 0 0 0 0 0 13 39 0 0 11 33
Donegan 11 11 0 11 100 V+T 4.57 13.14 8.29 0 9 82 2 18 0 0 0 0 0 0 0 0 0 0
El Alfy 17 17 0 0 0 – 4 16 10 – 0 0 0 0 0 0 0 0 17 100 0 0 0 0
Gupta 9 9 0 0 0 – 4.3 6.4 5.4 0.6 0 0 0 0 0 0 0 0 9 100 0 0 3 33
Karger 84 84 0 0 0 – 6 8 0 0 10 12 28 33 0 0 0 0 46 55 0 0 46 55
Kawakami 6 6 0 6 100 – 0 0 2.5 0 2 33 1 17 0 0 1 17 2 33 0 0 3 50
Luo 7 7 0 7 100 – – – 17.9 – 7 100 0 0 0 0 0 0 0 0 0 0 1 14
Masquelet 31 31 0 0 0 – 8 8 8 0 4 13 1 3 0 0 0 0 26 84 0 0 28 90
Moghaddam 50 50 0 50 100 V – – – – 17 34 9 18 0 0 0 0 22 44 2 4 0 0
Obert 9 9 0 – – – 8 52 24 – 3 33 4 44 0 0 0 0 2 22 0 0 3 33
Olesen 8 8 0 8 100 G+V – – 7 – 4 50 4 50 0 0 0 0 0 0 0 0 0 0
Scholz 13 13 0 13 100 G+-V 8 14 9.8 0 0 0 0 0 0 0 0 0 13 100 0 0 0 0
Stafford 27 27 0 27 100 G+-V 6 8 0 0 15 56 6 22 6 22 0 0 0 0 0 0 5 19
Taylor 69 69 0 68 98.6 V 1 96 11.2 13 – – – – – – – – – – – – 39 57%
Wang 32 32 0 32 100 G+V 6 14 8.6 – 18 56 4 13 4 13 0 0 0 0 0 0 5 16
Zappaterra 9 9 0 0 0 – 2.8 13.8 5 0 5 56 1 11 1 11 0 0 2 22 0 0 1 11
Weighted 6.32
mean
Total 427 427 0 267 62.5 94 22.0 72 16.9 11 2.6 1 0.2 152 35.6 2 0.5 156 36.5

Legend: %=% of total patients for each study; AIS=antibiotic-impregnated spacer; G=Gentamycin; V=Vancomycin; T=Tobramycin; Plast.Proc.=plastic procedures for soft tissue reconstruction.
 I. Morelli et al. / Injury, Int. J. Care Injured 47S6 (2016) S68–S76 S73

Table 7.
Masquelet technique – Second stage

Osteosynthesis 2° Weight bearing

stage after 2nd stage

N° Fix. Plate+ EF+ After n°

Articles Cases Change (%) Plate (%) Nail (%) Nail (%) Wires (%) EF (%) Nail (%) None (%) weeks No Partial Full

Apard 12 0 0 0 0 12 100 0 0 0 0 0 0 0 0 0 0 16 0 0 12
Azi 33 7 21 10 30 11 33 0 0 0 0 0 0 0 0 0 0 – – – –
Donegan 11 3 27 8 73 0 0 0 0 0 0 3 27 0 0 0 0 19 – – 11
El Alfy 17 0 0 0 0 0 0 0 0 0 0 17 100 0 0 0 0 0.3 0 17 0
Gupta 9 0 0 0 0 0 0 0 0 0 0 9 100 0 0 0 0 13 4 9 0
Karger 84 0 0 10 12 28 33 0 0 0 0 46 55 0 0 0 0 69.6 0 0 84
Kawakami 6 1 17 3 50 1 17 0 0 1 17 1 17 0 0 0 0 – – – –
Luo 7 0 0 7 100 0 0 0 0 0 0 0 0 0 0 0 0 – – – –
Masquelet 31 3 10 6 19 1 3 0 0 1 3 23 74 0 0 0 0 24 6 0 25
Moghaddam 50 22 44 26 52 22 44 0 0 0 0 1 2 0 0 1 2 – – – –
Obert 9 0 0 3 33 4 44 0 0 0 0 2 22 0 0 0 0 – – – –
Olesen 8 0 0 4 50 4 50 0 0 0 0 0 0 0 0 0 0 26.6 0 0 8
Scholz 13 5 38 3 23 2 15 0 0 0 0 8 62 0 0 0 0 – – – –
Stafford 27 0 0 15 56 6 22 6 22 0 0 0 0 0 0 0 0 24 0 8 19
Taylor 69 15 22 35 51 26 38 0 0 0 0 8 12 0 0 0 0 – – – –
Wang 32 29 91 19 59 0 0 4 13 0 0 3 9 5 16 1 3 30 0 0 32
Zappaterra 9 6 67 8 89 0 0 1 11 0 0 0 0 0 0 0 0 – – – –
Weighted Mean 20.92
Total 427 91 21 157 36.8 117 27.4 11 2.6 2 0.5 121 28.3 5 1.2 2 0.5

Legend: %=% of total patients for each study; Fix.Change=change of fixation devices; EF=external fixation.

to distraction osteogenesis. If soft tissue covering is insufficient, IMT
requires soft tissue reconstruction with help from the plastic surgical
team during the first step (43% of cases in this study), compared to
Ilizarov’s technique that allows distraction histogenesis [22].
Furthermore, IMT graft is less resistant to torsional and bending
stresses [22].
The IMT initially failed in 18% of patients, leading to additional
union procedures. After these, the overall failure rate was 10.3%,
including non-union (5.9%), amputation (4%) or persistent infection
(8.9%). Moreover, patients should be aware of the variable healing time
of IMT (range: 6–211 weeks after the second stage), frequent
complications and need of re-interventions.
Complications may occur in 49,6% of cases, including superfi-
cial and deep infections, failure of one or both steps (leading to
re-interventions), fixation hardware breakage, wound and soft tissues
healing problems, stiffness, malalignment and re-fractures [1–8,12,13].
The need of an additional union surgery (first step repetition, addition
of a fibular graft, switch to bone transport or other union techniques)
was a rare event in our study, as well as amputations [1–8,12]. However,
the 26.7% of the patients needed further minor surgeries (e.g. fixation
device substitutions or removal, and fixation of a stress fracture
occurred on the graft) [1–4,6–8,13]. The complications noted in this
study could be secondary to the different anatomical sites and local
environments that the technique has been applied, the learning curve
of the surgeon ( possibly initially performing suboptimal technique)
and the different underlying pathologies (aseptic, septic bone loss,
excision of tumors). Moreover, since the length of the defect has been
variable, different graft expanders have been used to fill in the defect

Table 8.
Bone graft details

Bone graft

N° Iliac Bone Add.

Articles Cases RIA (%) crest (%) Autol. (%) Allog. (%) DBM (%) DBB (%) subst. (%) graft (%) GF (%)

Apard 12 0 0 12 100 12 100 0 0 0 0 0 0 4 33 0 0 0 0

Azi 33 0 0 33 100 33 100 0 0 0 0 0 0 0 0 0 0 0 0
Donegan 11 1 9 3 27 6 55 5 45 10 91 0 0 0 0 1 9 9 82
El Alfy 17 0 0 17 100 17 100 0 0 0 0 0 0 0 0 0 0 0 0
Gupta 9 0 0 9 100 9 100 0 0 0 0 0 0 1 11 0 0 0 0
Karger 84 0 0 84 100 84 100 0 0 0 0 0 0 0 0 7 8 25 30
Kawakami 6 0 0 6 100 6 100 0 0 0 0 0 0 0 0 1 17 0 0
Luo 7 0 0 7 100 7 100 0 0 1 14 0 0 0 0 0 0 0 0
Masquelet 31 0 0 31 100 31 100 0 0 0 0 5 16 0 0 3 10 0 0
Moghaddam 50 50 100 13 26 50 100 0 0 0 0 0 0 50 100 0 0 50 100
Obert 9 4 44 5 56 9 100 0 0 0 0 0 0 0 0 0 0 0 0
Olesen 8 8 100 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Scholz 13 0 0 13 100 13 100 0 0 0 0 0 0 0 0 0 0 3 23
Stafford 27 27 100 5 19 27 100 23 85 0 0 0 0 0 0 0 0 23 85
Taylor 69 46 67 23 33 46 67 30 43 0 0 0 0 0 0 0 0 16 23
Wang 32 0 0 32 100 32 100 0 0 0 0 0 0 0 0 0 0 0 0
Zappaterra 9 1 11 7 78 9 100 0 0 0 0 0 0 3 33 1 11 2 22
Total 427 137 32.1 300 70.3 391 91.6 58 13.6 11 2.6 5 1.2 58 13.6 13 3.0 128 30.0

Legend: %=% of total patients for each study; RIA=Reamer Irrigator Aspirator; Autol.=autologous graft; Allog.=allogenous graft; DBM=Demineralized bone matrix.
DBB=Demineralized Bovine Bone; Bone subst.=synthetic bone substitutes; GF=Grouwth factors.
Add. graft=Additional Fibular autograft/other bone vascularized or non-vascularized autograft.
S74 I. Morelli et al. / Injury, Int. J. Care Injured 47S6 (2016) S68–S76

Table 9.
Complications

Compl.
Patients Complications

N° Superf. Deep Material Stiffness/ Wound and soft Donor

Articles Cases (%) SSI (%) SSI (%) failure (%) Failure (%) Malalign. (%) Refractures (%) decreased ROM (%) tissue disorders (%) site (%)

Apard 12 12 100 1 8 4 33 1 8 5 42 0 0 0 0 6 50 1 8 – –
Azi 33 33 100 0 0 4 12 0 0 7 21 0 0 1 3 23 70 1 3 4 12
Donegan 11 3 27 0 0 1 9 0 0 1 9 0 0 0 0 0 0 2 18 – –
El Alfy 17 17 100 10 59 0 0 1 6 9 53 4 24 1 6 6 35 0 0 4 24
Gupta 9 2 22 0 0 1 11 0 0 2 22 0 0 0 0 0 0 0 0 – –
Karger 84 42 50 0 0 0 0 0 0 8 10 15 18 0 0 19 23 0 0 0 0
Kawakami 6 5 83 0 0 1 17 0 0 0 0 0 0 0 0 0 0 4 67 – –
Luo 7 3 43 2 29 0 0 0 0 1 14 0 0 0 0 0 0 0 0 1 14
Masquelet 31 14 45 1 3 0 0 0 0 9 29 0 0 4 13 0 0 0 0 – –
Moghaddam 50 16 32 0 0 3 6 3 6 7 14 0 0 0 0 0 0 8 16 0 0
Obert 9 4 44 0 0 1 11 0 0 3 33 0 0 0 0 2 22 0 0 – –
Olesen 8 5 63 0 0 0 0 0 0 3 38 2 25 0 0 0 0 0 0 0 0
Scholz 13 5 38 2 15 0 0 0 0 0 0 1 8 0 0 2 15 0 0 – –
Stafford 27 4 15 0 0 0 0 0 0 4 15 0 0 0 0 0 0 0 0 0 0
Taylor 69 23 33 0 0 4 6 0 0 12 17 0 0 0 0 0 0 7 10 – –
Wang 32 15 47 5 16 0 0 0 0 6 19 3 9 0 0 1 3 0 0 12 38
Zappaterra 9 9 100 0 0 0 0 2 22 0 0 0 0 0 0 6 67 1 11 – –
Total 427 212 49.6 21 4.9 19 4.4 7 1.6 77 18.0 25 5.9 6 1.4 65 15.2 24 5.6 21 5

Legend: %=% of total patients for each study; Compl. Patients=patients presenting complications; SSI=surgical site infection; Malalign.=Malalignment; ROM=Range of Motion.

with no standardised ratios used for optimum bone graft integration.
All of the above issues should be taken into consideration for future
studies.
Few of the studies analysed reported the direct complications of
graft harvesting in the donor site. All of them occurred after the iliac
crest harvesting and included: 13 cases of prolonged donor site pain, 2
hypertrophic scars, 2 infections, 4 sensory disturbances [15,17–19].
Nevertheless, donor site complications change the morbidity rate
associated with IMT, and should be considered among its drawbacks.
The complication rate for bone harvest using the RIA technique
performed in the intramedullary canal of femur and tibia (not
specifically for IMT) is 6% [11]. This includes fractures, injury of the
anterior cortex of both bones, injury to the knee joint, heterotopic
ossifications, and hypertrophic scars [23–27].
Complication rate for iliac crest bone grafting is 19.37% [11],
specifically hematoma formation, seromas and deep infections (often
requiring aspiration and debridement re-interventions), fractures of
the anterior superior iliac spine or of the iliac wing, persistent donor
site pain for more than 6 months, iatrogenic cutaneous nerve injuries,
and superior gluteal artery injuries [25,28–37]. Rarely heterotopic
ossifications, injury of the sacro-iliac joint, abdominal hernia and
gluteus maximus insertion detachment may occur [32,33,38–44].
Furthermore, the volume of defect may dictate the site of bone harvest,
as larger defects require a higher volume of bone graft which can be
harvested from RIA, whereas a smaller volume can be obtained from
the anterior or posterior iliac crest [11].
Limitations
Searching the medical literature, only 17 papers meet the inclusion
criteria, with few articles reaching a sufficient reliability in terms of
follow up and number of cases. Only five out of seventeen papers

Table 10.
Re-interventions

Further surgeries

Additional
N° Other union
Articles Cases Surgeries (%) surgery (%) Amputations (%)

Apard 12 8 67 1 8 0 0
Azi 33 5 15 6 18 1 3
Donegan 11 1 9 0 0 0 0
El Alfy 17 2 12 9 53 0 0
Gupta 9 0 0 2 22 0 0
Karger 84 24 29 6 7 6 7
Kawakami 6 7 117 1 17 0 0
Luo 7 1 14 1 14 0 0
Masquelet 31 36 116 4 13 2 6
Moghaddam 50 0 0 1 2 3 6
Obert 9 0 0 2 22 1 11
Olesen 8 0 0 2 25 0 0
Scholz 13 5 38 0 0 0 0
Stafford 27 0 0 1 4 1 4
Taylor 69 16 23 5 7 4 6
Wang 32 6 19 0 0 0 0
Zappaterra 9 3 33 0 0 0 0
Total 427 114 26.7 41 9.6 18 4.2

Legend: %=% of total patients for each study.

 I. Morelli et al. / Injury, Int. J. Care Injured 47S6 (2016) S68–S76 S75

Table 11.
Outcomes and follow up

Infections healed Time to heal (weeks) Follow up (months)

Non
Infect. N° union/ Non After
cases Yes (%) No (%) Cases Union % amput. % union % Amput. % Min Max Mean SD stage Min Max Mean SD

Apard 7 6 85.7 1 14.3 12 11 91.7 1 8.3 1 8.3 0 0.0 48 376 158 111.2 ns 12 94 39.5 27.8
Azi 23 16 69.6 7 30.4 33 30 90.9 3 9.1 2 6.1 1 3.0 16 60 34 9.2 1 12 61 27 15.9
Donegan 4 3 75.0 1 25.0 11 10 90.9 1 9.1 1 9.1 0 0.0 – – 32.29 0 2 12 48 – –
El Alfy 17 15 88.2 2 11.8 17 14 82.4 3 17.6 3 17.6 0 0.0 24 76 40 – 2 14 38 23 –
Gupta 8 6 75.0 2 25.0 9 6 66.7 3 33.3 0 0.0 0 0.0 32 52 42 – 2 18 24 21.5 –
Karger 41 41 100.0 0 0.0 84 76 90.5 8 9.5 2 2.4 6 7.1 – – 57.6 0 1 12 264 – –
Kawakami 6 6 100.0 0 0.0 6 6 100.0 0 0.0 0 0.0 0 0.0 12 24 15.33 4.68 2 36 72 50.7 0
Luo 7 7 100.0 0 0.0 7 7 100.0 0 0.0 0 0.0 0 0.0 – – – – – 41 150 86.7 37.2
Masquelet 24 22 91.7 2 8.3 31 29 93.5 2 6.5 0 0.0 2 6.5 – – 16 0 ns 12 168 – –
Moghaddam 35 32 91.4 3 8.6 50 40 80.0 10 20.0 7 14.0 3 6.0 12 60 34.40 11.6 2 12 12 12 0
Obert 0 – – – – 9 6 66.7 3 33.3 2 22.2 1 11.1 12 56 32 – ns 12 – – –
Olesen 3 3 100.0 0 0.0 8 8 100.0 0 0.0 0 0.0 0 0.0 23.7 40.7 31.77 7.01 ns 9 20.8 13.2 –
Scholz 13 13 100.0 0 0.0 13 13 100.0 0 0.0 0 0.0 0 0.0 12 24 18.92 – ns 9 24 13 0
Stafford 7 6 85.7 1 14.3 27 24 88.9 3 11.1 2 7.4 1 3.7 – – – 0 ns 12 12 12 0
Taylor 7 5 71.4 2 28.6 69 62 89.9 7 10.1 5 7.2 2 2.9 6 208 26.6 29.3 2 12 64 23.8 14.2
Wang 32 32 100.0 0 0.0 32 32 100.0 0 0.0 0 0.0 0 0.0 12 36 19.6 7.35 ns 24 32 27.5 –
Zappaterra 3 3 100.0 0 0.0 9 9 100.0 0 0.0 0 0.0 0 0.0 18.4 210.8 64.04 63.76 2 6 52.7 16.01 15.94
Weighted Mean 15.75
Total 237 216 91.1 21 8.9 427 383 89.7 44 10.3 25 5.9 16 4

Legend: %=% of total patients for each study; amput.=amputations; ns=non specified.

selected were prospective studies [6,12,16,19,20]. Few studies gave
detailed patient information, such as patient comorbidities and
pharmacological history.
Due to insufficient data on confounding factors, we are unable to
make further interpretations regarding the studies, for example the use
of a vascular fibular graft will not doubt improve union rates and
therefore this would not be attributable to the IMT only. Other
confounding factors include the lack of distinction between post-
traumatic defects (acute bone loss) and aseptic pseudoarthroses
following a fracture, whilst some studies only reported one or the
other. Therefore, it was necessary to combine such groups together
during analysis, combining (i) osteomyelitis and septic non-unions
as “infection,” and (ii) “post-traumatic defect” including fractures,
pseudoarthroses and acute bone losses, with or without the presence
of infection. Similarly, the healing time reported started from the first
step in one study, the second in five papers, while the starting point
was not reported in 4 articles.
The presence of such few studies dealing with IMT, not considering
the great variability in reporting data, made a meta-analysis study
impossible.
Conclusions
Strategies related to bone repair are evolving aiming to reduce the
time to union, morbidity and functional impairment [45–51].
To our knowledge, this is the first systematic review concerning the
IMT in the medical literature. IMT seems to be effective in infection
eradication and in the treatment of non-unions even if employed for
large bone defects (>20 cm). Further studies are needed to confirm this
result, calculate the impact of surgical variants and patient-associated
variables to the outcomes of IMT.
Declaration of conflicting interests
All named authors hereby declare that they have no conflicts of
interest to disclose.
Funding statement
This research received no specific grant from any funding agency in
the public, commercial, or not-for-profit sectors
Ethical approval
Not required
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