Injury, Int. J.

Care Injured 48 (2017) 206–213

Contents lists available at ScienceDirect

Injury
journal homepage: www.elsevier.com/locate/injury

CME review article

Limb reconstruction after traumatic bone loss

Mukai Chimutengwende-Gordon a,*, Abubaker Mbogo b, Wasim Khan a, Richard Wilkes c
a
Institute of Orthopaedics and Musculoskeletal Science, Royal National Orthopaedic Hospital, Brockley Hill, Stanmore HA7 4LP, UK
b
North Manchester General Hospital, Delaunays Road, Crumpsall, Manchester M8 5RB, UK
c
Limb Reconstruction Unit, Hope Hospital, Stott Lane, Salford, Lancashire M6 8HD, UK

A R T I C L E I N F O A B S T R A C T

Article history: A variety of options exist to reconstruct limbs following traumatic bone loss. The management of these
Accepted 17 November 2013 injuries is challenging and often requires prolonged and potentially painful treatment. The Ilizarov
technique of bone transport using circular external fixators is widely used for limb reconstruction of
Keywords: large bone defects. Other techniques include vascularised fibular grafting, the use of induced
Bone defects pseudosynovial membranes combined with cancellous autologous bone grafts and the use of autologous,
Ilizarov technique allogeneic or synthetic bone grafts on their own for smaller defects. Future directions include further
Vascularised fibular grafts
research on bone tissue engineering using stem cell therapy and growth factors such as bone
Limb reconstruction
morphogenetic proteins. The purpose of this Continuing Medical Education article is to describe the key
limb reconstructive techniques that may be employed to treat traumatic bone loss. In particular, this
article is intended to serve as a revision tool for those preparing for postgraduate examinations.
ß 2013 Elsevier Ltd. All rights reserved.

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
Initial assessment and management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Internal fixation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
External fixation and bone transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Vascularised bone grafts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208
Other strategies for the reconstruction of bone defects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Autologous and allogeneic bone grafts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Demineralised bone matrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
Masquelet technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
Metal cages loaded with bone graft materials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
Synthetic bone graft substitute materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
Custom made endoprosthetic replacement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
Bone tissue engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Multiple choice questions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213

Introduction whether an injured limb is salvageable is based on the extent of

muscle, bone and joint damage as well as the potential for
The reconstruction of limbs following significant traumatic bone neurological and vascular recovery [1]. Historically, primary
loss is challenging and often technically difficult. The decision as to amputation was frequently used to manage fractures with signifi-
cant bone loss [2,3]. In modern times, a variety of bone reconstruc-
tion treatment strategies to regenerate bone loss and restore
* Corresponding author. Tel.: +44 208 909 5300; fax: +44 208 420 7392.
function exist. These treatment strategies include autologous bone
E-mail addresses: mukai.cg@mac.com, mukai.gordon@gmail.com grafting (for defects less than 5 cm in size) [4], bone transport using
(M. Chimutengwende-Gordon). Ilizarov frames and monolateral external fixators and the Masquelet

http://dx.doi.org/10.1016/j.injury.2013.11.022
0020–1383/ß 2013 Elsevier Ltd. All rights reserved.

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 M. Chimutengwende-Gordon et al. / Injury, Int. J. Care Injured 48 (2017) 206–213
technique which combines induced membranes and cancellous
autologous bone grafts [4,5].
The tibia is the site most frequently associated with traumatic
bone loss as a result of its subcutaneous position [3]. Significant
traumatic bone loss is often caused by high-energy injuries and is
most commonly seen in males [3]. These injuries may be
associated with severe soft tissue injuries and polytrauma [3,6].
There is no widely employed specific classification to describe
traumatic bone loss [6]. Salai et al. classified bone loss according to
whether the injury was open or closed, the size of the bone defect
and the type of bone defect (articular or non-articular) [7]. Gustilo
and Anderson’s classification is commonly employed to describe
open fractures. This classification is based on the degree of soft
tissue injury and contamination which are indicators of the risk of
infection [8]. Robinson et al. classified tibial fractures with bone
loss as trivial, minor, moderate and severe according to whether
the defect was a wedge or circumferential and the maximal length
of bone loss. This classification could potentially be applied to
other long bone fractures [6,9].
Initial assessment and management
The initial assessment and management of patients with severe
limb injuries should follow Advanced Trauma Life Support
principles [10]. Debridement of soft tissue and bone is the first
step in the treatment of limbs deemed to be salvageable [6]. A
plastic surgeon should be consulted early in cases where there is
significant soft tissue loss. The joint British Association of Plastic
Reconstructive and Aesthestic Surgeons/British Orthopaedic As-
sociation (BAPRAS/BOA) standards for the management of open
fractures of the lower limb, recommend that a multidisciplinary
team including both orthopaedic and plastic surgeons in a
specialist centre is required for the treatment of complex open
fractures [10]. Initial skeletal stabilisation may be undertaken with
a temporary external fixator [6].
Internal fixation
If bone loss is limited, immediate definitive internal fixation may
be an option depending on the condition of the soft tissues. Plate
fixation with bridging of bone defects combined with bone grafting
may be performed [6]. Minimally invasive plate osteosynthesis
(MIPO) is an alternative technique to standard plate fixation which
aims to reduce iatrogenic soft tissue damage, avoid disruption of the
vascular supply and fracture haematoma, hence reducing infection
rates and providing improved biological healing [11–13]. Endo et al.
reported successful outcomes in a series of three cases (five limbs)
where once sufficient callus formation had been detected, external
fixation was converted to the MIPO technique using a locking
compression plate to shorten the external fixation wearing period in
femoral lengthening [14]. Intramedullary nailing of long bone
fractures is an option that can provide good skeletal stability and
limb alignment and may allow early joint movement [6]. Acute
shortening may be considered and the limb may be subsequently re-
lengthened [6,15]. It has been recommended that tibial fractures
with more than 3 cm bone loss should be closed gradually to avoid
neurovascular compromise [15,16].
External fixation and bone transport
Bone transport is widely used in limb reconstructive surgery.
Bone transport using external fixators as described by Gavrill
Ilizarov has revolutionised the management of long bone defects
[17,18]. This technique allows simultaneous treatment of large bone
defects, soft tissue loss, infection and leg-length discrepancy
[17,19,20]. The Ilizarov technique uses circular external fixators
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207
which consist of rings and connecting rods. Partial rings and arches
are useful when working near joints and they allow access to
traumatic wounds. Rings of a smaller diameter are more stable than
larger rings. 2 cm of space should be left circumferentially between
the ring and the skin to allow for possible limb swelling. The stability
is also increased by having a smaller distance between rings, using
two rings instead of one for each bone segment and increasing the
wire diameter. At least four connecting rods between the rings and at
least two wires per ring are necessary [20].
The use of a ring external fixator and tensioned wires allows early
weight bearing as it provides greater support than a monolateral
frame [21]. The top rings allow force to be transferred through the
external frame and to bypass the bone defect [21]. Although this
technique uses the ring fixator, the use of a monolateral half-pin
frame may produce successful bone transport [22].
Ilizarov described the use of a corticotomy, which is a low-energy
osteotomy of the cortex, with preservation of the local blood supply
to both the periosteum and the medullary canal. Ilizarov believed
that this enhanced bone formation. The ends of the corticotomy are
gradually brought together while distraction occurs at the defect
site. A period of latency ranging from three to 10 days is instituted
before distraction is commenced and following corticotomy. This
latency period is generally considered to enhance bone formation
[22]. The shorter periods are sufficient for the classic Ilizarov
corticotomy, however the longer periods may be required if a
traditional osteotomy that has disrupted the medullary canal is
performed [22]. As an adjunct to Ilizarov’s technique, some surgeons
may chose to use strategies such as insertion of autologous bone
marrow grafting and demineralised bone matrix in order to improve
healing of the corticotomy/osteotomy [23].
Ilizarov carried out experiments in a canine tibial model in
order to gain a better understanding of osteogenesis during limb
lengthening as well as to study the changes in soft tissues
undergoing elongation [19,24]. These studies concluded that the
rate and frequency of distraction are important to osteogenesis
under the influence of the ‘Tension–Stress’ effect. The ‘Tension–
Stress’ effect refers to the phenomenon that when tissues are
subjected to gradual, steady traction stresses are created resulting
in the tissues becoming metabolically activated. Provided there is
adequate blood supply there is stimulation of proliferative and
biosynthetic cellular functions and tissue regeneration [19,24]. The
most favourable results were achieved with a distraction rate of
1.0 mm per day in four equal increments (0.25 mm every six hours)
combined with stable external fixation [19,24]. Clinical studies
confirmed that this technique promoted osteogenesis in humans
but it was noted that the rate and frequency of distraction may
have to be adjusted depending on factors such as the quality of
bone formed and the response of the soft tissues [25]. Figs. 1 and 2
are radiographs of patients treated with the Ilizarov technique.
This technique requires long-term placement of external fixators
and may be associated with complications [17]. Neurovascular
damage is a potential immediate complication but may be avoided
with thorough knowledge of the anatomy [20]. Pin site infection is a
common complication that occurs in the majority patients
undergoing limb lengthening with external fixation [26]. The risk
of serious complications such as soft tissue contracture, joint
contracture or subluxation may be minimised with good preopera-
tive planning. Late complications such as chronic recurrent pin-site
infections, osteomyelitis, premature union, delayed or non-union,
hardware failure, reflex sympathetic dystrophy, late bowing and
failure may occur [20]. There should be extensive preoperative
education of the patient and their family in order to increase
compliance as the treatment is lengthy and may be painful [22].
The Taylor spatial frame (TSF) is a modern multiplanar external
fixator that may be used for bone transport and is based on the
Ilizarov principle. The rings are connected by six telescopic struts
[(Fig._1)TD$IG]
208 M. Chimutengwende-Gordon et al. / Injury, Int. J. Care Injured 48 (2017) 206–213

Fig. 1. (a and b) Non union after tibial nailing. Note loss of medial cortex over a segment of tibia. (c) Proximal tibial corticotomy with Ilizarov frame on tibia (d and e) Ilizarov
frame on tibia for bone transport. A segmental excision of tibia has been undertaken and the Ilizarov frame has been used to transport a segment of tibia across the resulting
gap. Note the consolidating regenerate bone proximally and the distal docking site. (f) End result. Consolidated regenerate and united docking site.

at special universal joints [27]. The strut lengths are adjusted using
a computer programme which facilitates accurate fracture
reduction. Use of the TSF also allows simultaneous correction of
different deformities such as rotation, angulation and translation
[27,28]. A number of clinical studies have reported favourable
outcomes with the TSF in terms of healing of traumatic bone
defects and deformity correction [27,29–32].
Bone transport may be carried out over an intramedullary nail
in order to allow better control of length and alignment, earlier
removal of the external fixator and to add increased rigidity to the
construct [5]. Motorised intramedullary lengthening nails may be
used independently for bone transport as an alternative to external
fixation. This technique has the advantage of avoiding complica-
tions associated with external fixation and has the potential to
result in fast rehabilitation and improved cosmetic results [33–
35]. Bone transport with an external fixator in combination with
locking plate fixation has also been described [5].
Vascularised bone grafts
Free vascularised bone transfer may be used when simpler
techniques available for reconstruction have either failed or are
expected to fail [36]. Vascularised bone grafts participate actively in
bony union and are able to hypertrophy in response to applied stress
and increase the rate and percentage of union [2,36]. This is due to
the fact that the osteocytes and other cells within vascularised
autologous grafts maintain their viability due to preserved endosteal
vascular flow as well as muscular and periosteal blood flow [36].
The fibula is the most commonly used donor site for
vascularised bone grafts as it has a constant blood supply,
transfer is straightforward and it can provide up to 30 cm of
length without leading to significant donor site morbidity. The
use of a vascularised fibula graft may be considered for managing
bone defects larger than 10 cm, smaller defects that have failed to
heal with non-vacsularised bone grafting and previously infected
bone non-union with or without a defect associated with
osteonecrosis [2,36]. Other donor sites available for vascularised
bone transfer include the iliac crest based on the deep circumflex
iliac artery, the radius based on the radial artery, the humerus
based on the posterior radial collateral artery and the medial
femoral condyle based on the descending geniculate artery. Graft
size from these alternative sites is limited. A disadvantage of the
use of vascularised bone grafts in general is that they are
frequently a poor structural replacement for metaphyseal and
diaphyseal bone defects due to size and/or shape mismatch,
especially for defects of the femur, tibia and humerus. As a result,
rigid internal fixation, external fixation, addition of structural
allografts or a long period of non-weightbearing or bracing may
be necessary [37]. Other disadvantages include the need for
microvascular skills, a long operative time, the risk of necrosis
due to anastomotic complications, donor site morbidity and
stress fracture [38,39].

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[(Fig._2)TD$IG] M. Chimutengwende-Gordon et al. / Injury, Int. J. Care Injured 48 (2017) 206–213 209

Fig. 2. (a and b) Gunshot injury with proximal tibial bone loss treated by distal to proximal bone transport with an Ilizarov frame. (c and d) End result after frame removal.

Careful preoperative planning is required prior to vascularised
fibula grafting. It is important to evaluate both the recipient and
donor sites. Clinical assessment (or if any doubt vascular imaging)
should determine that there are vessels of sufficient calibre close to
the recipient site and ideally situated in relatively unscarred tissue.
The vascular supply of the donor leg must be assessed to be
adequate [36]. Other considerations include the method of
anastomosis to be used i.e. whether antegrade or retrograde, end-
to-end or end-to-side and whether to use a vein graft [40]. For tibial
bone defects, the contralateral fibula is often used for vascularised
grafts as the ipsilateral fibula may be missing, fractured or
surrounded by damaged or heavily scarred tissue [36]. However,
use of the ipsilateral fibula may be considered as it has the advantage
of retaining its vascularity without the need for the use of
microvascular surgical techniques [41]. For femoral defects, the
ipsilateral fibula is generally used and for upper limb defects, the
fibula from either side is used depending on the ease of patient
positioning [36].
Several studies have demonstrated the efficacy of vascularised
fibula grafts. Minami et al. reviewed the outcomes of 104 vascu-
larised fibula grafts in 102 patients and reported that bony union
was achieved in 95% of cases (with 84% of cases uniting primarily).
Fourteen cases were complicated by early postoperative thrombosis
but all were treated successfully with thrombectomy and vein
grafting. Infection recurred in two of 23 patients who had
osteomyelitis and a bone defect at two and six months. In 15 cases
stress fractures of the graft occurred [40]. Falder et al. performed a
retrospective analysis on a series of 32 consecutive patients who
underwent free vascularised fibula grafting for large bone defects
and reported an overall success rate of 91%. Additionally, they
measured hypertrophy of the graft radiographically and found that
the fibula hypertrophied in all cases where there was mechanical
stress through the recipient bone [42]. Zhen et al. reported results of
free vascularised grafting in 38 patients with tibial shaft fractures, of
which 10 were open and 28 were closed fractures. 31 fractures
healed within 18–24 weeks, whereas seven healed within 28–41
weeks. There were no cases of nonunion or infection [43].
Other strategies for the reconstruction of bone defects
Autologous and allogeneic bone grafts
Autologous bone graft has the advantage of possessing osteo-
genicity, osteoinductivity and osteoconductivity [44]. However, it is
limited in size may be associated with donor site morbidity and
prolonged operative time. As a result autologous bone graft may not
be ideal for the treatment of large traumatic bone defects
[45]. Allogeneic grafts may be used to avoid donor site morbidity
as well as prolonged external fixation [6]. Allogeneic grafts may be
harvested from human cadaveric bone and cryopreserved to reduce
antigenicity [37]. Large defects may be treated and the bone defect
size and shape may be closely matched with allograft [7,37]. Imme-
diate stability may be achieved by combining the use of allograft
with internal fixation [37]. However, as the bone is non-viable, the
complications associated with the use of allograft include delayed or
non-union, infection and stress fracture [37].

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210 M. Chimutengwende-Gordon et al. / Injury, Int. J. Care Injured 48 (2017) 206–213
Demineralised bone matrix
Demineralised bone matrix (DBM) is an acid-extracted organic
matrix obtained from allogeneic bone graft [46]. It contains
collagens (mainly type I), non-collagenous proteins, growth factors,
1–6% residual calcium phosphate mineral and a small amount of
cellular debris. DBM has osteoconductive and osteoinductive
properties [46]. However, the osteoinductive capacity of commer-
cially available DBM preparation is variable depending on the
preparation used [47].
Masquelet technique
The Masquelet technique consists of a combination of the
induction of a pseudosynovial membrane and autologous cancellous
bone grafting. This technique may be used to reconstruct extensive
diaphyseal bone loss up to 25 cm in length and consists of two stages
[4,48]. The first stage consists of soft tissue debridement with
implantation of a cement spacer at the site of the defect and
stabilisation with an external fixator. The soft tissue envelope is
repaired. The second stage is undertaken approximately two months
later and involves removing the cement spacer carefully to avoid
disturbing the membrane that has formed. The defect is filled with
autologous cancellous bone graft and the bone is usually stabilised
with internal fixation [4,48]. The induced membrane prevents the
resorption of bone graft. Histological and immunochemical assess-
ment has shown that the induced membrane becomes highly
vascularised and secretes growth and osteoinductive factors such as
vascular endothelial growth factor (VEGF), transforming growth
factor beta 1(TGF b1) and bone morphogenetic protein 2 (BMP-2)
[49]. There are numerous clinical case series that have demonstrated
satisfactory outcomes in terms of bone healing and limb function
with this technique [49–53].
Metal cages loaded with bone graft materials
The use of morselised bone graft within a metal cage is another
treatment option for bone defects. Bullens et al. used a segmental
diaphyseal femoral bone defect goat model to assess this
technique. The defects were reconstructed with either a stainless
steel cage filled with morselised allograft or with a structural
cortical autograft (n = 6). This technique allowed full weight
bearing and resulted in superior biological characteristics with
histological analysis showing complete replacement of the
morselised graft with new viable bone [54]. The same research
group found in an in vitro mechanical study that titanium cages
and stainless steel mesh cages filled with morselised bone graft
were stable in dynamic loaded conditions [55]. Clinical case
reports and small case series of the use of titanium cages filled with
bone graft (stabilised with either intramedullary nails or plates) to
treat femoral, tibial and humeral defects have shown promising
results. Plain radiographic evidence of satisfactory limb alignment
as well as computer tomography demonstration of bone ingrowth
throughout cages has been reported [56–59].
Synthetic bone graft substitute materials
Synthetic bone graft substitute materials such as the calcium
phosphate ceramics hydroxyapatite (HA) and tricalcium phosphate
(TCP) have osteoconductive properties [44]. TCP is useful for filling
small bone defects [44]. HA has been used successfully to fill larger
bone defects. Disadvantages of these materials are that they may
require a long time for complete integration and replacement by
newly formed bone, there may be difficulties in implanting them,
they are unable to fill irregular gaps and they lack growth factors
[44].
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Custom made endoprosthetic replacement
Endoprosthetic replacement (EPR), which was originally
designed for the management of bone tumours, has the potential
to play a limited role as a reconstructive option following trauma
[60–62]. Mohammed et al. reported a case of a patient with a
12 cm traumatic femoral bone defect that was managed using a
custom made EPR [62]. A satisfactory functional outcome was
achieved and at three years follow-up the patient was indepen-
dently mobile and able to drive a car. Additionally, the functional
score according to the Musculoskeletal Tumour Society–Interna-
tional Symposium on Limb Salvage System was 70% and the
Toronto Extremity Salvage Score was 62% [62]. Clinical and
functional assessment of eight patients who underwent EPR for
failed internal fixation of proximal femoral fractures indicated
that EPR may be an effective salvage procedure [60]. However, at
present, the data on the utility of this technique for management
of traumatic bone loss is limited.
Bone tissue engineering
Bone tissue engineering may have a role in treatment of
traumatic bone defects. The ‘diamond concept’ refers to the need
for consideration of the interaction between four factors for
successful bone regeneration. These four factors are osteogenic
cells, osteoconductive scaffolds, growth factors as well as the
stability of the mechanical environment [63,64]. One tissue
engineering approach is the use of stem cells that may be
harvested from adult bone marrow and may be expanded in vitro.
The use of stem cells may be limited by the fact that the number of
stem cells that may be harvested and the time required to expand
them is variable [65,66]. The technique used for bone marrow
aspiration has been shown to affect the number of stem cells
obtained. Muschler et al. recommended that the volume of bone
marrow aspiration from any one site should not be greater than
2 ml because larger volumes result in dilution of the bone-marrow
sample with peripheral blood and a reduction in the concentration
of osteoblast progenitor cells [66].
Scaffold materials that have been used to provide a structural
template for new tissue to form include naturally derived polymers
(e.g. collagen and hyaluronan), synthetic polymers (e.g. polyanhy-
drides, polycaprolactones, polylactic acid and polyglycolic acid),
ceramics and polymer–ceramic composites [67]. In order to
achieve new bone formation, these supportive scaffolds may be
loaded with osteogenic cells and growths factors such as bone
morphogenetic proteins (BMPs), platelet-derived growth factor
(PDGF), transforming factor-b (TGF-b), insulin-like growth factor-
1(IGF-1), vascular endothelial growth factor (VEGF) or fibroblast
growth factor (FGF) [68].
BMPs have been studied extensively and may be considered to
be the most important growth factors for bone healing due to their
potent osteoinductive properties [68,69]. With the exception of
BMP-1, BMPs are members of the TGF-b superfamily and were
discovered by Urist in 1965 [69,70]. They have been shown to
enhance new bone formation in a number of preclinical studies and
a smaller number of clinical trials but their use may be limited due
to costs [65,71–77]. The BMP-2 Evaluation in Surgery for Tibial
Trauma (BESTT) trial was a prospective single-blind randomised
controlled trial including 450 patients with open tibial fractures.
The study assessed the safety and efficacy of recombinant human
(rh) BMP-2 use and found that rhBMP-2 accelerated fracture
healing, reduced the need for secondary interventions and
decreased the infection rate [77]. Several smaller clinical trials
assessing the effect of BMP-7 on healing of fracture non-unions
have also shown promising results [78–83]. BMP therapy,
(potentially in combination with more established treatment
 M. Chimutengwende-Gordon et al. / Injury, Int. J. Care Injured 48 (2017) 206–213
strategies), may be indicated for management of critical size bone
defects and requires continued exploration [84]. Determination
and delivery of optimum dosages of BMPs is another area requiring
further research [68]. More clinical studies are needed to fully
assess the benefits and the safety of bone tissue engineering
strategies in general [65].
Conclusion
The decision to salvage a severely injured limb must take into
account the degree of muscle and bone loss as well as the degree of
vascular and neurological injury. It is recommended that patients
with traumatic bone loss and accompanying significant soft tissue
injury are managed in a specialist centre with combined orthopaedic
and plastic surgical care. Limb reconstruction techniques are often
challenging and patients should be counselled about the potential
complications and the often long duration of treatment.
Conflict of interest statement
The authors of ‘Limb Reconstruction after Traumatic Bone Loss’
do not have any conflicts of interest regarding the material
discussed within the manuscript.
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Injury Editorial Office
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Multiple choice questions
For each question, choose whether statements are true or false:
(1) Ilizarov Technique: Distraction Osteogenesis
(a) A distraction rate of 3 mm per day is optimal.
(b) The original Ilizarov technique includes the insertion of
bone graft or DBM at the defect site to improve healing.
(c) Decreased ring diameter is associated with an increase in
stability of circular external fixators.
(d) Early weight bearing may be achieved with the Ilizarov
frame.
(e) The use of a monolateral half-pin frame may be used for
distraction osteogenesis.
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213
(2) Bone tissue engineering
(a) The ‘triangular concept’ of tissue engineering should be
used to achieve successful bone regeneration.
(b) Treatment of fractures with BMP-2 has been associated
with a reduced rate of infection.
(c) In order to obtain adequate numbers of stem cells from
bone marrow aspirates, the volume of aspirates should be
greater than 2 ml.
(d) The use of BMP-9 has been shown clinically to enhance
bone formation in traumatic tibial bone defects.
(e) Scaffolds for bone tissue engineering should ideally possess
adequate mechanical properties for load bearing.
(3) Bone graft substitutes
(a) DBM consists predominantly of collagen type III.
(b) DBM is both osteoconductive and osteoinductive.
(c) Calcium phosphate ceramics act primarily as osteoinduc-
tive agents.
(d) Calcium phosphate ceramics are able to closely match
irregular shapes.
(e) Collagen-based matrices are useful for filling metaphyseal
bone defects.
(4) Masquelet technique
(a) Has a limited role in reconstruction of bone defects greater
than 8 cm.
(b) The induced pseudosynovial membranes have been shown
to secrete growth factors.
(c) Cortical bone graft is used to fill the defect.
(d) Additional bone graft substitute may be used if there is
insufficient autologous bone graft.
(e) The induced membrane prevents resorption of the bone
graft.
(5) Vascularised fibular grafting
(a) May be used to bridge defects up to 30 cm in length.
(b) The graft matches the shape of the defect well when used
for lower limb bone loss.
(c) Is not useful for treating upper limb bone defects.
(d) Is contraindicated for treating previously infected non-
unions with segmental bone loss.
(e) An ipsilateral fibular graft is generally used for traumatic
tibial bone defects.