Injury, Int. J.

Care Injured 47S6 (2016) S68–S76

Contents lists available at ScienceDirect

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 tissues and necrotic bone to bleeding healthy tissue (“paprika sign”),
The induced membrane technique (IMT) firstly described by and the use of a polymethyl methacrylate (PMMA) cement spacer
Masquelet et al. is a two-step procedure to treat bone defects and placed in the bony defect, which is stabilised with a temporary external
non-unions [1]. Masquelet describes an initial debridement of soft 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
* Corresponding author at: Dr. Ilaria Morelli Department of Reconstructive Surgery and
pseudo-synovial membrane, as a result of a foreign body reaction [9].
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. After 6–8 weeks, the second step is undertaken. The induced
E-mail address: [email protected] (Ilaria Morelli). 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 S69

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

Fig. 1. PRISMA IPD flow diagram.

S70 I. Morelli et al. / Injury, Int. J. Care Injured 47S6 (2016) S68–S76

papers then underwent a full-text analysis before deeming if undergoing the procedure was grouped into discrete categories;
appropriate for inclusion in the systematic review and meta-analysis. tumour, infection (included osteomyelitis and septic non-unions),
Specific information was obtained from the included studies, such and post-traumatic defect (including fractures, where possible further
as the patients’ demographics (age, gender), comorbidities (diabetes, classified in cases undergoing surgery due to aseptic non-unions or
rheumatoid arthritis, BMI, cigarette smoking, chronic use of steroids, acute bone losses) (Table 2).
NSAIDs, bisphosphonates), aetiology, history of previous surgery before Bone defects primarily affected the tibia (287, 67.2%), followed by
index procedure, and duration from the trigger event to IMT surgery. fibula (55, 12.9%) and femur (83, 19.4%) (Table 3). The metaphysis was
We classified the bone involvement (tibia, fibula, femur, humerus, involved in 62 (14.5%) defects, and were a combination of cylindrical
radius, ulna, clavicle), defect size (cm), shape (conical/non segmental, (116; 27.2%) and conical shapes (29; 6.8%) [3,5,8,15]. The mean size of
cylindrical/segmental), and site (diaphysis, metaphysis) [3,21]. the defects was 5.53 cm, and classified according to Karger’s class: I
Regarding the surgical procedure we determined the variation of (<2 cm) in 15 defects, II (2–5 cm) in 99, III (5–10 cm) in 114 and IV
the techniques used during the first and second stage, which included (>10 cm) in 61 [3] (Table 4). Further pre-operative information is
various spacer types, fixation techniques ( plate, nail, plate and nail, available in Table 5.
antibiotic-coated nail, wires, external fixator), bone graft use (RIA, iliac Following debridement during the first stage, antibiotics were
crest, allografts, bone substitutes, demineralized bone matrix/bovine added to the spacer in the majority of patients (267, 62.5%), which was
bone, growth factors, vascularized or non-vascularized fibular auto- most often combined with external fixation (152, 35.6%) and soft tissue
graft), use of systemic antibiotics, need for soft tissue reconstruction, reconstruction (156, 36.5%) (Table 6). During the second stage,
duration between stages, and rehabilitation regime. definitive fixation was frequently undertaken with either a plate
The main outcome measures were progression to bone union (157; 36.8%), an intramedullary nail (117; 27.4%) or an external fixator
and infection eradication. Complications included failure of either the (121; 28.3%). In the 21% of cases, the fixation device was substituted
first or second stage (resulting in definitive or temporary non-union during the second stage (Table 7). The sources of bone graft were RIA
until a second union surgery was performed), material failure (e.g. (from various sites) (137; 32.1%), and/or the iliac crest (300; 70.3%).
breaking of an intramedullary nail), re-fractures, decreased range of Allogenic graft was used in 58 patients (13.6%), and the addition of
motion, superficial and deep infections, disorders in wound and soft growth factors was used in 128 patients (30%) (Table 8).
tissues healing. The need for repeated interventions, amputations and Complications were high (49.6%) amongst all studies, occurring
additional union procedures were also assessed. in 15% to 100% of patients (we often found more than a complication
Data was analyzed using SPSS statistics software (version 21, 2013, per case) (Table 9). The main complications weresuperficial (21; 4.9%)
IBM Corporation, New York, USA). A descriptive statistical analysis and deep surgical site infections (19; 4.4%), failure of one of the IMT
was carried out on the aggregate data. Univariate analysis was steps ( persistence of infections or non unions, 77, 18%), with
undertaken to determine risk of non-union and failure to eradicate subsequent requirement for further union surgery or another kind of
infection using unpaired t-test, Fischer’s exact test and Chi square test intervention in 41 (9.6%) and 114 (26.7%) patients respectively (Table
where applicable. 10). However, at the last follow-up, infection was eradicated in 216
patients (91.1% of patients with an osteomyelitis), and 383 patients
Results (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
Six hundred and twenty-eight papers were initially identified and (Table 11).
screened (Figure 1). After duplicates were excluded, 19 studies were Minimal information was available regarding individual patient
read in full to assess their relevance to this study. Seventeen studies [1– data in the included studies (137 patients). Based on the reported IPD,
8,12–20] reporting aggregate data met our inclusion criteria, with 427 we undertook a univariate analysis to determine the variables
patients undergoing IMT. associated to infection eradication, bone union, need for re-interven-
The mean age of included patients was 39.03 (range 15–84), and tions and presence of complications. Given the small numbers, only the
included substantially more males (353, 82.7%), with a mean follow-up need of further union surgeries was significantly associated to poorer
of 15.75 months (range 6–264) (Table 1). The main reasons for 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 infection eradication 91.1%, although 33 (7.7%) among these patients
complications ( p < 0.001 and p = 0.001, respectively). Finally, patients needed an additional union procedure to heal. Therefore, the present
undergoing IMT because of bone infections had a higher risk of surgical analysis confirms the ability of the IMT to achieve the two main goals
complications ( p < 0.001). There was no difference in type of fixation it is commonly used for, despite its application in very large bone
used or modes of bone grafting. defects.
Comparing it to other bone reconstruction techniques effective for
Discussion defects over 20 cm, such as Ilizarov bone transport, IMT has the
advantage that the healing time is independent from the defect length
Masquelet et al. first presented the induced membrane technique [22]. Avoiding the use of an external frame for prolonged periods of
in 1986, publishing a case series 14 years later [1]. The technique time, IMT is generally better accepted and can be used in less compliant
underwent several changes, and has been employed in different patients [22]. Moreover, it does not require a microsurgical approach
contexts and different methodology. but there is an option of utilizing vascularized fibular grafts for less
This is, to our knowledge the first systematic review aimed at responsive bones (osteomyelitic or irradiated bones) [10,22]. To achieve
analysing the results of the application of the IMT in septic and aseptic bone union in large segmental defects, bone substitutes as tricalcium
non-unions, osteomyelitis, traumatic bone losses and tumor resections phosphate (not exceeding a 1:3 ratio) and BMP7 have been added to
in adult patients. the graft to improve its osteoconductivity and osteoinductivity [10,22].
The bone defects ranged from 0.6 to 26 cm [12]. Overall, the mean However, IMT needs two invasive surgical procedures, which may
union rate found in this systematic review was 89.7% and the rate of 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 re-interventions), fixation hardware breakage, wound and soft tissues
requires soft tissue reconstruction with help from the plastic surgical healing problems, stiffness, malalignment and re-fractures [1–8,12,13].
team during the first step (43% of cases in this study), compared to The need of an additional union surgery (first step repetition, addition
Ilizarov’s technique that allows distraction histogenesis [22]. of a fibular graft, switch to bone transport or other union techniques)
Furthermore, IMT graft is less resistant to torsional and bending was a rare event in our study, as well as amputations [1–8,12]. However,
stresses [22]. the 26.7% of the patients needed further minor surgeries (e.g. fixation
The IMT initially failed in 18% of patients, leading to additional device substitutions or removal, and fixation of a stress fracture
union procedures. After these, the overall failure rate was 10.3%, occurred on the graft) [1–4,6–8,13]. The complications noted in this
including non-union (5.9%), amputation (4%) or persistent infection study could be secondary to the different anatomical sites and local
(8.9%). Moreover, patients should be aware of the variable healing time environments that the technique has been applied, the learning curve
of IMT (range: 6–211 weeks after the second stage), frequent of the surgeon ( possibly initially performing suboptimal technique)
complications and need of re-interventions. and the different underlying pathologies (aseptic, septic bone loss,
Complications may occur in 49,6% of cases, including superfi- excision of tumors). Moreover, since the length of the defect has been
cial and deep infections, failure of one or both steps (leading to 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. requiring aspiration and debridement re-interventions), fractures of
All of the above issues should be taken into consideration for future the anterior superior iliac spine or of the iliac wing, persistent donor
studies. site pain for more than 6 months, iatrogenic cutaneous nerve injuries,
Few of the studies analysed reported the direct complications of and superior gluteal artery injuries [25,28–37]. Rarely heterotopic
graft harvesting in the donor site. All of them occurred after the iliac ossifications, injury of the sacro-iliac joint, abdominal hernia and
crest harvesting and included: 13 cases of prolonged donor site pain, 2 gluteus maximus insertion detachment may occur [32,33,38–44].
hypertrophic scars, 2 infections, 4 sensory disturbances [15,17–19]. Furthermore, the volume of defect may dictate the site of bone harvest,
Nevertheless, donor site complications change the morbidity rate as larger defects require a higher volume of bone graft which can be
associated with IMT, and should be considered among its drawbacks. harvested from RIA, whereas a smaller volume can be obtained from
The complication rate for bone harvest using the RIA technique the anterior or posterior iliac crest [11].
performed in the intramedullary canal of femur and tibia (not
specifically for IMT) is 6% [11]. This includes fractures, injury of the Limitations
anterior cortex of both bones, injury to the knee joint, heterotopic
ossifications, and hypertrophic scars [23–27]. Searching the medical literature, only 17 papers meet the inclusion
Complication rate for iliac crest bone grafting is 19.37% [11], criteria, with few articles reaching a sufficient reliability in terms of
specifically hematoma formation, seromas and deep infections (often 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 Ethical approval
detailed patient information, such as patient comorbidities and
pharmacological history. Not required
Due to insufficient data on confounding factors, we are unable to
make further interpretations regarding the studies, for example the use References
of a vascular fibular graft will not doubt improve union rates and
therefore this would not be attributable to the IMT only. Other [1] Masquelet AC, Fitoussi F, Begue T, Muller GP. [Reconstruction of the long bones
by the induced membrane and spongy autograft]. Ann Chir Plast Esthet 2000;45:
confounding factors include the lack of distinction between post-
346–53.
traumatic defects (acute bone loss) and aseptic pseudoarthroses [2] Apard T, Bigorre N, Cronier P, Duteille F, Bizot P, Massin P. Two-stage reconstruction of
following a fracture, whilst some studies only reported one or the post-traumatic segmental tibia bone loss with nailing. Orthop Traumatol Surg Res
other. Therefore, it was necessary to combine such groups together 2010;96:549–53.
[3] Karger C, Kishi T, Schneider L, Fitoussi F, Masquelet AC. French Society of Orthopaedic S,
during analysis, combining (i) osteomyelitis and septic non-unions
et al. Treatment of posttraumatic bone defects by the induced membrane technique.
as “infection,” and (ii) “post-traumatic defect” including fractures, Orthop Traumatol Surg Res 2012;98:97–102.
pseudoarthroses and acute bone losses, with or without the presence [4] Taylor BC, Hancock J, Zitzke R, Castaneda J. Treatment of bone loss with the
of infection. Similarly, the healing time reported started from the first induced membrane technique: techniques and outcomes. J Orthop Trauma
step in one study, the second in five papers, while the starting point 2015;29:554–7.
[5] Stafford PR, Norris BL. Reamer-irrigator-aspirator bone graft and bi Masquelet technique
was not reported in 4 articles. for segmental bone defect nonunions: a review of 25 cases. Injury 2010;41(Suppl 2):
The presence of such few studies dealing with IMT, not considering S72–7.
the great variability in reporting data, made a meta-analysis study [6] Zappaterra T, Ghislandi X, Adam A, Huard S, Gindraux F, Gallinet D, et al. [Induced
impossible. membrane technique for the reconstruction of bone defects in upper limb. A prospective
single center study of nine cases]. Chir Main 2011;30:255–63.
[7] Donegan DJ, Scolaro J, Matuszewski PE, Mehta S. Staged bone grafting following
Conclusions placement of an antibiotic spacer block for the management of segmental long bone
defects. Orthopedics 2011;34:e730–5.
Strategies related to bone repair are evolving aiming to reduce the [8] Kawakami R, Konno S, Ejiri S, Hatashita S. Surgical treatment for infected long bone
defects after limb-threatening trauma: application of locked plate and autogenous
time to union, morbidity and functional impairment [45–51].
cancellous bone graft. Fukushima J Med Sci 2015;61:141–8.
To our knowledge, this is the first systematic review concerning the [9] Pelissier P, Masquelet AC, Bareille R, Pelissier SM, Amedee J. Induced membranes secrete
IMT in the medical literature. IMT seems to be effective in infection growth factors including vascular and osteoinductive factors and could stimulate bone
eradication and in the treatment of non-unions even if employed for regeneration. J Orthop Res 2004;22:73–9.
[10] Giannoudis PV, Faour O, Goff T, Kanakaris N, Dimitriou R. Masquelet technique for the
large bone defects (>20 cm). Further studies are needed to confirm this
treatment of bone defects: tips-tricks and future directions. Injury 2011;42: 591–8.
result, calculate the impact of surgical variants and patient-associated [11] Dimitriou R, Mataliotakis GI, Angoules AG, Kanakaris NK, Giannoudis PV. Complications
variables to the outcomes of IMT. following autologous bone graft harvesting from the iliac crest and using the RIA: a
systematic review. Injury 2011;42(Suppl 2):S3–15.
Declaration of conflicting interests [12] Moghaddam A, Zietzschmann S, Bruckner T, Schmidmaier G. Treatment of atrophic tibia
non-unions according to “diamond concept”: Results of one- and two-step treatment.
Injury 2015;46(Suppl 4):S39–50.
All named authors hereby declare that they have no conflicts of [13] Scholz AO, Gehrmann S, Glombitza M, Kaufmann RA, Bostelmann R, Flohe S, et al.
interest to disclose. Reconstruction of septic diaphyseal bone defects with the induced membrane technique.
Injury 2015;46(Suppl 4):S121–4.
Funding statement [14] Olesen UK, Eckardt H, Bosemark P, Paulsen AW, Dahl B, Hede A. The Masquelet technique
of induced membrane for healing of bone defects. A review of 8 cases. Injury 2015;46
(Suppl 8):S44–7.
This research received no specific grant from any funding agency in [15] Azi ML, Teixeira A, Cotias RB, Joeris A, Kfuri M. Membrane induced osteogenesis in the
the public, commercial, or not-for-profit sectors management of post-traumatic bone defects. J Orthop Trauma 2016.
S76 I. Morelli et al. / Injury, Int. J. Care Injured 47S6 (2016) S68–S76

[16] Obert L, Rondot T, Cheval D, Morris M, Sergent P, Leclerc G, et al. Application of the [34] Kalk WW, Raghoebar GM, Jansma J, Boering G. Morbidity from iliac crest bone harvesting.
induced membrane in the acute setting of bone loss. Techniques in Orthopaedics J Oral Maxillofac Surg 1996;54:1424–9; discussion 30.
2016;31:23–8. [35] Arrington ED, Smith WJ, Chambers HG, Bucknell AL, Davino NA. Complications of iliac
[17] LuoTD, Nunez FA, Jr., Lomer AA, Nunez FA, Sr. Management of recalcitrant osteomyelitis and crest bone graft harvesting. Clin Orthop Relat Res 1996:300–9.
segmental bone loss of the forearm with the Masquelet technique. J Hand Surg Eur 2016. [36] Goulet JA, Senunas LE, DeSilva GL, Greenfield ML. Autogenous iliac crest bone graft.
[18] Wang X, Luo F, Huang K, Xie Z. Induced membrane technique for the treatment of bone Complications and functional assessment. Clin Orthop Relat Res 1997:76–81.
defects due to post-traumatic osteomyelitis. Bone Joint Res 2016;5:101–5. [37] Sawin PD, Traynelis VC, Menezes AH. A comparative analysis of fusion rates and donor-
[19] El-Alfy BS, Ali AM. Management of segmental skeletal defects by the induced membrane site morbidity for autogeneic rib and iliac crest bone grafts in posterior cervical fusions.
technique. Indian J Orthop 2015;49:643–8. J Neurosurg 1998;88:255–65.
[20] Gupta G, Ahmad S, Mohd Z, Khan AH, Sherwani MK, Khan AQ. Management of traumatic [38] Fernyhough JC, Schimandle JJ, Weigel MC, Edwards CC, Levine AM. Chronic donor site
tibial diaphyseal bone defect by “induced-membrane technique”. Indian J Orthop pain complicating bone graft harvesting from the posterior iliac crest for spinal fusion.
2016;50:290–6. Spine (Phila Pa 1976) 1992;17:1474–80.
[21] Sales de Gauzy J, Fitoussi F, Jouve JL, Karger C, Badina A, Masquelet AC, et al. Traumatic [39] Banwart JC, Asher MA, Hassanein RS. Iliac crest bone graft harvest donor site morbidity. A
diaphyseal bone defects in children. Orthop Traumatol Surg Res 2012;98:220–6. statistical evaluation. Spine (Phila Pa 1976) 1995;20:1055–60.
[22] Lasanianos NG, Kanakaris NK, Giannoudis PV. Current management of long bone large [40] Swan MC, Goodacre TE. Morbidity at the iliac crest donor site following bone grafting of
segmental defects. Orthop Trauma 2009;24:149–63. the cleft alveolus. Br J Oral Maxillofac Surg 2006;44:129–33.
[23] Lowe JA, Della Rocca GJ, Murtha Y, Liporace FA, Stover MD, Nork SE, et al. Complications [41] Freilich MM, Sandor GK. Ambulatory in-office anterior iliac crest bone harvesting. Oral
associated with negative pressure reaming for harvesting autologous bone graft: a case Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:291–8.
series. J Orthop Trauma 2010;24:46–52. [42] Thome C, Leheta O, Krauss JK, Zevgaridis D. A prospective randomized comparison of
[24] Quintero AJ, Tarkin IS, Pape HC. Technical tricks when using the reamer irrigator aspirator rectangular titanium cage fusion and iliac crest autograft fusion in patients undergoing
technique for autologous bone graft harvesting. J Orthop Trauma 2010;24: 42–5. anterior cervical discectomy. J Neurosurg Spine 2006;4:1–9.
[25] Belthur MV, Conway JD, Jindal G, Ranade A, Herzenberg JE. Bone graft harvest using a new [43] Baqain ZH, Anabtawi M, Karaky AA, Malkawi Z. Morbidity from anterior iliac crest bone
intramedullary system. Clin Orthop Relat Res 2008;466:2973–80. harvesting for secondary alveolar bone grafting: an outcome assessment study. J Oral
[26] McCall TA, Brokaw DS, Jelen BA, Scheid DK, Scharfenberger AV, Maar DC, et al. Treatment Maxillofac Surg 2009;67:570–5.
of large segmental bone defects with reamer-irrigator-aspirator bone graft: technique [44] Borrelli J, Jr., Leduc S, Gregush R, Ricci WM. Tricortical bone grafts for treatment of
and case series. Orthop Clin North Am 2010;41:63–73; table of contents. malaligned tibias and fibulas. Clin Orthop Relat Res 2009;467:1056–63.
[27] Newman JT, Stahel PF, Smith WR, Resende GV, Hak DJ, Morgan SJ. A new minimally [45] Giannoudis PV, Gudipati S, Harwood P, Kanakaris NK. Long bone non-unions trea-
invasive technique for large volume bone graft harvest for treatment of fracture ted with the diamond concept: a case series of 64 patients. Injury 2015;46(Suppl 8):
nonunions. Orthopedics 2008;31:257–61. S48–54.
[28] Ahlmann E, Patzakis M, Roidis N, Shepherd L, Holtom P. Comparison of anterior and [46] Shimizu T, Akahane M, Morita Y, Omokawa S, Nakano K, Kira T, et al. The regeneration
posterior iliac crest bone grafts in terms of harvest-site morbidity and functional and augmentation of bone with injectable osteogenic cell sheet in a rat critical fracture
outcomes. J Bone Joint Surg Am 2002;84-A:716–20. healing model. Injury 2015;46:1457–64.
[29] Ito Z, Matsuyama Y, Sakai Y, Imagama S, Wakao N, Ando K, et al. Bone union rate with [47] Ollivier M, Gay AM, Cerlier A, Lunebourg A, Argenson JN, Parratte S. Can we achieve bone
autologous iliac bone versus local bone graft in posterior lumbar interbody fusion. Spine healing using the diamond concept without bone grafting for recalcitrant tibial
(Phila Pa 1976) 2010;35:E1101–5. nonunions? Injury 2015;46:1383–8.
[30] Kloen P, Wiggers JK, Buijze GA. Treatment of diaphyseal non-unions of the ulna and [48] Zura R, Della Rocca GJ, Mehta S, Harrison A, Brodie C, Jones J, et al. Treatment of chronic
radius. Arch Orthop Trauma Surg 2010;130:1439–45. (>1 year) fracture nonunion: heal rate in a cohort of 767 patients treated with low-
[31] Pollock R, Alcelik I, Bhatia C, Chuter G, Lingutla K, Budithi C, et al. Donor site morbidity intensity pulsed ultrasound (LIPUS). Injury 2015;46:2036–41.
following iliac crest bone harvesting for cervical fusion: a comparison between minimally [49] Perez Nunez MI, Ferreno Blanco D, Alfonso Fernandez A, Casado de Prado JA, Sanchez
invasive and open techniques. Eur Spine J 2008;17:845–52. Crespo M, De la Red Gallego M, et al. Comparative study of the effect of PTH (1-84) and
[32] Dai LY, Jiang LS. Single-level instrumented posterolateral fusion of lumbar spine with strontium ranelate in an experimental model of atrophic nonunion. Injury
beta-tricalcium phosphate versus autograft: a prospective, randomized study with 3-year 2015;46:2359–67.
follow-up. Spine (Phila Pa 1976) 2008;33:1299–304. [50] Alkhawashki HM. Shock wave therapy of fracture nonunion. Injury 2015;46:2248–52.
[33] Rajan GP, Fornaro J, Trentz O, Zellweger R. Cancellous allograft versus autologous bone [51] Schützenberger S, Kaipel M, Schultz A, Nau T, Redl H, Hausner T. Non-union site
grafting for repair of comminuted distal radius fractures: a prospective, randomized trial. debridement increased the efficacy of rhBMP-2 in a rodent model. Injury 2014;45:
J Trauma 2006;60:1322–9. 1165–70.