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Definitive fixation in the first stage of the induced membrane technique for septic segmental bone defects. Why not?

Published:December 30, 2022DOI:https://doi.org/10.1016/j.jcot.2022.102089

      Abstract

      Background

      Infected segmental bone defects (I-SBD) are challenging and complex to manage. This study aimed to show the outcomes achieved in I-SBD of the femur and tibia, treated with the induced membrane technique performing a definitive bone stabilization in the first stage.

      Methods

      We retrospectively reviewed 30 patients with infected non-articular segmental bone defects of the femur (n = 11) and tibia (n = 19), operated consecutively between January 2015 and May 2021. The need for fixation exchange, bone defect length, allo/autograft ratio used, bone healing, reoperation (discriminating between mechanical and infection-related causes), and failure rates (graft resorption or nonunion) were recorded.

      Results

      Fixation in the first stage was performed with 28 (93.33%) intramedullary nails, ten coated with antibiotic cement, and 2 (6.67%) locked plates. None were removed during the second stage of the technique. The mean length of the bone defects was 5cm (range 3.5–12). The most commonly used allo-/autograft ratio was 50-50. The bone healing rate was 93.33% (n = 28), with a median follow-up of 7 months (range 3–12). The reoperation rate due to mechanical instability was 3.33% (n = 1) and for recurrence of infection was 10.0% (n = 3). The overall failure rate was 6.67% (n = 2). The median follow-up was 42 months (range 12–85).

      Conclusion

      Masquelet technique appears feasible and effective in treating infected segmental bone defects of the femur and tibia. Definitive fixation at the first stage showed a success rate of 93.33%, with a re-operation rate of 10.0% related to infection.

      Keywords

      1. Introduction

      Infected segmental bone defects (I-SBD) are one of the most complex injuries to treat.
      • Metsemakers W.J.
      • Fragomen A.T.
      • Moriaty T.F.
      • et al.
      Fracture-Related Infection (FRI) consensus group. Evidence-based recommendations for local antimicrobial strategies and dead space management in fracture-related infection.
      ,
      • Norris B.L.
      • Vanderkarr M.
      • Sparks Ch
      • Chitnis A.S.
      • Ray B.
      • Holy C.E.
      Treatments, cost and healthcare utilization of patients with segmental bone defects.
      The staged technique described by Masquelet represents one approach to dealing with them.
      • Norris B.L.
      • Vanderkarr M.
      • Sparks Ch
      • Chitnis A.S.
      • Ray B.
      • Holy C.E.
      Treatments, cost and healthcare utilization of patients with segmental bone defects.
      • Masquelet A.C.
      • Fitoussi F.
      • Begue T.
      • Muller G.P.
      Reconstruction of the long bones by the induced membrane and spongy autograft.
      • Masquelet A.C.
      • Begue T.
      The concept of induced membrane for reconstruction of long bone defects.
      It consists of a thorough surgical debridement, the placement of a cement spacer to fill the bone defect (around which a reactive membrane will grow), and its stabilization with external fixation. In the second stage, the spacer is removed, the lesion is definitively stabilized, and the defect is filled with an autologous cancellous bone graft.
      • Masquelet A.C.
      • Fitoussi F.
      • Begue T.
      • Muller G.P.
      Reconstruction of the long bones by the induced membrane and spongy autograft.
      • Masquelet A.C.
      • Begue T.
      The concept of induced membrane for reconstruction of long bone defects.
      • Masquelet A.
      • Kanakaris N.K.
      • Obert L.
      • Stafford P.
      • Giannoudis P.V.
      Bone repair using the Masquelet technique.
      • Giannoudis P.V.
      • Faour O.
      • Goff T.
      • Kanakaris N.
      • Dimitriou R.
      Masquelet technique for the treatment of bone defects: tips-tricks and future directions.
      Different modifications of the original description have been reported with the current popularization of the technique.
      • Giannoudis P.V.
      • Faour O.
      • Goff T.
      • Kanakaris N.
      • Dimitriou R.
      Masquelet technique for the treatment of bone defects: tips-tricks and future directions.
      • Mathieu L.
      • Durand M.
      • Collombet J.M.
      • Rousiers A.
      • I’Escalopier N.
      • Masquelet A.C.
      Induced membrane technique: a critical literature analysis and proposal for a failure classification scheme.
      • Morelli I.
      • Drago L.
      • George D.A.
      • Gallazzi E.
      • Scarponi S.
      • Romanó C.L.
      Masquelet technique: myth or reality? A systematic review and meta-analysis.
      • Giannoudis P.V.
      • Harwood P.J.
      • Tosounidis T.
      • Kanakaris N.K.
      Restoration of long bone defects treated with the induced membrane technique: protocol and outcomes.
      • Morwood M.P.
      • Streufert B.D.
      • Bauer A.
      • et al.
      Intramedullary nails yield superior results compared with plate fixation when using the Masquelet technique in the femur and tibia.
      • Pesciallo C.A.
      • Garabano G.
      • Dainotto T.
      • Ernst G.
      Masquelet technique in post-traumatic infected femoral and tibial segmental bone defects. Union and reoperation rates with high proportions (up to 64%) of allograft in the second stage.
      Definitive fixation with devices other than an external fixator during the first stage is one of them.
      • Wang X.
      • Luo F.
      • Huang K.
      • Xie Z.
      Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis.
      • Apard T.
      • Bigorre N.
      • Cronier P.
      • Duteille F.
      • Bizot P.
      • Massin P.
      Two-stage reconstruction of post-traumatic segmental tibia bone loss with nailing.
      • Ayouba G.
      • Lemonne F.
      • Kombate N.K.
      • Bakriga B.
      • Yaovi Edem J.
      • Andre-Pierre Max U.
      Interest of nailing associated with the Masquelet technique in reconstruction of bone defect.
      It has been mostly reported in aseptic bone defects, showing certain benefits such as not hindering the performance of soft tissue coverage, avoiding the associated risk of pin tract infection, allowing early rehabilitation, and decreasing bone healing time.
      • Wang X.
      • Luo F.
      • Huang K.
      • Xie Z.
      Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis.
      ,
      • Ayouba G.
      • Lemonne F.
      • Kombate N.K.
      • Bakriga B.
      • Yaovi Edem J.
      • Andre-Pierre Max U.
      Interest of nailing associated with the Masquelet technique in reconstruction of bone defect.
      There have been few reports on this modification technique in I-SBD, perhaps due to the possibility of biofilm formation around the implant and the risk of infection recurrence.
      • Mathieu L.
      • Durand M.
      • Collombet J.M.
      • Rousiers A.
      • I’Escalopier N.
      • Masquelet A.C.
      Induced membrane technique: a critical literature analysis and proposal for a failure classification scheme.
      ,
      • Bose D.
      • Kugan R.
      • Stubbs D.
      • McNally M.
      Management of infected nonunion of the long bones by a multidisciplinary team.
      ,
      • Blanchette K.A.
      • Wenke J.C.
      Current therapies in treatment and prevention of fracture wound biofilm: why a multifacet approach is essential for resolving persistent infections.
      Therefore, this study aimed to assess the results regarding bone healing, reoperations, and failure rates in treating infected segmental bone defects of the femur and tibia with the induced membrane technique, performing a definitive bone fixation in the first stage.

      1.1 Methods

      We retrospectively reviewed our department's database, identifying all consecutive patients treated between January 2012 and May 2021 with the Masquelet technique for a femoral or tibial segmental bone defect. This study was carried out after obtaining approval from the ethics committee of our hospital (Protocol number 7517).
      The inclusion criteria were patients older than 18 years with I-SBD who underwent definitive fixation at the first stage of the Masquelet technique. Patients with aseptic bone defects, bone defects secondary to oncological resection, articular bone defects, and those who did not fulfill a minimum follow-up of 12 months from the second stage were excluded.
      The defect was considered infected in the presence of two positive cultures with the same microorganism of two intraoperative bone samples or the presence of a positive culture together with the presence of a fistula or intraoperative pus.
      • Metsemakers W.J.
      • Morgenstern M.
      • McNally M.A.
      • et al.
      Fracture-related infection: a consensus on definition from an international expert group.
      For histological confirmation of infection, we used the criteria established by Morgersten et al.
      • Morgenstern M.
      • Athanasou N.A.
      • Ferguson J.Y.
      • Metsemakers W.J.
      • Atkins B.L.
      • McNally M.A.
      The value of quantitative histology in the diagnosis of fracture-related infection.
      Overall, based on the inclusion and exclusion criteria, 30 of 57 patients were eligible to participate (27 were excluded: 6 had aseptic bone defects, ten had not completed both stages of treatment, seven did not achieve the minimum follow-up, two because the defect had been due to oncological resection, one because definitive stabilization wasn't performed in the first stage, and one because the bone defect affected the distal epiphysis of the femur).
      The study population included 30 patients, 21 men and nine women, with a median age of 40 years (range 18–68). Bone defects affected the femur in 11 (36.67%) cases and the tibia in 19 (63.33%). Patient descriptions are summarized in Table 1.
      Table 1Patients’ demographics, preoperative data and first stage result.
      PatientsGender/AgeComorbInjury (bone Gustillo)Time from injury to Masquelt (months)Prev surgFixation method (first stage)ATB spacerSoft tissue coverage
      1M 62F141PlateV
      2F 45T93PlateV
      3M 40F133A-IMNVG
      4F 65F173IMNV
      5M 60F165IMNV
      6F 47F132IMNV
      7F 60SF211IMNV
      8F 18DMF323IMNV
      9M 19F–3B241IMNV
      10M 23OF-3A162A-IMNVG
      11M 41F-284A-IMNVG
      12M 23F95IMNVG
      13M 36ST-3B83IMNVCross-leg
      14M 18T-2122IMNV
      15M 40T 3B207IMNVVAC, skin graft
      16M 68DMT96A-IMNVGVAC, skin graft
      17M 51T-3A162A-IMNVLMF
      18M 18T-295IMNTVAC, skin graft
      19F 24ST-3A22IMNVLMF
      20M 35T-2162IMNVLMF
      21M 64T-3A273A-IMNVG
      22M 45T-3B123IMNVGLMF
      23M 34T-3B213IMNVVAC, cross-leg
      24F 41T162IMNV
      25F 47T-3B122A-IMNVLMF
      26M 18T122A-IMNV
      27M 19ST-3A73IMNVGLMF
      28M 47T-3A103A-IMNVGLMF
      29M 32T-3B114IMNVGLMF
      30M 35T-3A122A-IMNVGLMF
      F: female; M: male T: tibia; F: femur; S: smoking; DM: diabetes mellitus; O: Obesity – Body Mass Index >30; Prev surg: number of surgeries previous to Masquelet technique, IMN: intramedullary nail; A-IMN: intramedullary nail coated with antibiotic cement; Plate: two locked plates; V: vancomycin, G: gentamicin; GV: gentamicin + vancomycin; T: tobramycin; LMF: local muscle flap; VAC: vacuum-assistance closure .

      1.2 Surgical procedures

      First stage: the previous osteosynthesis was removed entirely. An aggressive debridement with resection of all infected/dead bone and soft tissues was performed until a vital surgical bed and bleeding bone ends were obtained. The medullary canal was reamed and flushed. Bone and soft tissue samples were sent for bacteriological (at least 5) and histological analysis (at least 3). According to the location of the bone defect, an intramedullary nail or a locked plate, restoring alignment, length, and rotation of the limb was used for fixation. In cases where a nail was implanted, it was statically locked with the appropriate diameter and length to yield a definitive fixation. In patients with plate fixation and with the same goal, a minimum of three locked screws were placed on each side of the defect. Then, it was filled with surgical cement (adding 2 g of antibiotic per dose) (Fig. 1). Primary wound closure, or if necessary, an appropriate soft tissue coverage procedure, was performed.
      Fig. 1
      Fig. 1a: Intraoperative image showing ATB-nail fixation at the first stage. B: cement spacer placement around the intramedullary nail.
      After this stage, progressive weight-bearing was allowed according to tolerance, using crutches. The patients received empirical broad-spectrum intravenous antibiotic (ATB) therapy until microbiological sensitivity results were obtained, at which time they were shifted to a specific ATB regimen. Then, they continued oral treatment, as indicated and monitored by the infectious disease department.
      Second stage: The second stage was performed after an ATB-free period of two weeks. The spacer was explanted, and the bony ends of the defect were curetted. We also used this second time to remove non-viable tissue and repeat sampling for microbiology. We then grafted the defect using autograft (harvested from the homolateral iliac crest) and allograft. The latter was provided by the institution's bone and tissue bank. It was delivered to the operating room, morselized, defatted, frozen, and non-irradiated. The amounts and proportions of allo-autograft used were systematically recorded in each surgery. Specific flasks tabulated in cubic centimeters were used for this purpose. Finally, the induced membrane was hermetically closed.
      Postoperatively, immediate weight-bearing was allowed, according to the progression of the clinical and radiological signs of bone healing.
      Postoperative clinical and radiological follow-up examinations were performed every two weeks after the first stage and at three weeks, 3, 6, 12, 18, and 24 months, continuing annually after that.

      1.3 Data

      From the first stage, we recorded information regarding the type of implant used for definitive fixation, ATB added to cement spacer, and soft tissue coverage procedures (if any). The results of surgical samples sent for bacteriological or histological analysis, reoperations, and the time elapsed between stages were also registered.
      In the second stage, we analyzed the size of the bone defect and the need for exchange or augmentation (addition of a locked plate) of the osteosynthesis implanted at the first stage. We also recorded the allo-autograft ratio used and the bone healing time.
      The need for reoperations and their cause (mechanical and infection-related causes), healing, and failure rate were registered at the end of the study. We used the WOMAC score
      • Bellamy N.
      • Buchanan W.W.
      • Goldsmith C.H.
      • Campbell J.
      • Stitt L.W.
      Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee.
      (by telephone interview at the close of the study) to assess the functional outcomes.
      Bone healing was defined when 3 of 4 cortices showed bone bridges joining the ends of the defect on postoperative anteroposterior (AP) and lateral (L) radiographs, with the absence of pain under weight-bearing.
      • Giannoudis P.V.
      • Faour O.
      • Goff T.
      • Kanakaris N.
      • Dimitriou R.
      Masquelet technique for the treatment of bone defects: tips-tricks and future directions.
      Infection remission was defined as the absence of clinical (discharge, warm skin, swelling, pain) and radiological signs/symptoms related to infection, together with normalization of erythrocyte sedimentation rate and C reactive protein values.
      • Wang X.
      • Luo F.
      • Huang K.
      • Xie Z.
      Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis.
      Treatment failure was defined as the lack of bone healing and/or graft resorption.
      • Giannoudis P.V.
      • Harwood P.J.
      • Tosounidis T.
      • Kanakaris N.K.
      Restoration of long bone defects treated with the induced membrane technique: protocol and outcomes.
      ,
      • Pesciallo C.A.
      • Garabano G.
      • Dainotto T.
      • Ernst G.
      Masquelet technique in post-traumatic infected femoral and tibial segmental bone defects. Union and reoperation rates with high proportions (up to 64%) of allograft in the second stage.

      1.4 Statistical analysis

      A descriptive analysis of the series was performed. Continuous variables were expressed as mean and standard deviation or median and range according to their distribution. Categorical variables were expressed as frequency and percentage.

      1.5 Results

      Locked plates were used in two (6.67%) cases and intramedullary nails in 28 (93.33%) cases (of which ten - 40% - were coated with ATB cement) for bone fixation on the first stage.
      Vancomycin was the most frequent ATB added to the spacer in 18 (60.00%) patients. (Table 1). Fourteen (46.67%) cases needed soft tissue coverage reconstructions.
      Staphylococcus aureus was the most frequently (36.67%) isolated microorganism from intraoperative samples (Table 2). Four (13.33%) patients had negative cultures, three had an active fistula, and all had intraoperative pus. Histological findings compatible with infection were observed in all patients.
      Table 2Microbiology, defect size, grafting, and outcomes.
      PatientsMicrobilogyDefect size(cm)Allo:auto %Reoperat infectionReoperat instabilityTime to union (months)Follow-up
      1CNS4.555:45750
      2SA3.550:50734
      3(−)550:501242
      4CNS550:50860
      5SA650:50932
      6(−)6.560:40744
      7(−)6.552:48650
      8SA1058:42Failure85
      9POLI
      • Masquelet A.C.
      • Begue T.
      The concept of induced membrane for reconstruction of long bone defects.
      1464:36982
      10SA1265:35Y1216
      11PA4.545:55Failure14
      12SA4.530:70732
      13PA450:50Y6.540
      14SA3.550:50655
      15(−)3.559:41Y1075
      16POLI
      • Metsemakers W.J.
      • Fragomen A.T.
      • Moriaty T.F.
      • et al.
      Fracture-Related Infection (FRI) consensus group. Evidence-based recommendations for local antimicrobial strategies and dead space management in fracture-related infection.
      3.550:50653
      17POLI
      • Norris B.L.
      • Vanderkarr M.
      • Sparks Ch
      • Chitnis A.S.
      • Ray B.
      • Holy C.E.
      Treatments, cost and healthcare utilization of patients with segmental bone defects.
      3.550:50660
      18E455:456.528
      19POLI
      • Masquelet A.C.
      • Fitoussi F.
      • Begue T.
      • Muller G.P.
      Reconstruction of the long bones by the induced membrane and spongy autograft.
      453:47Y6.532
      20SA4.555:45722
      21CNS550:50831
      22CNS655:45742
      23CNS550:506.545
      24SA4.556:44680
      25E750:50624
      26CNS650:50756
      27POLI
      • Masquelet A.
      • Kanakaris N.K.
      • Obert L.
      • Stafford P.
      • Giannoudis P.V.
      Bone repair using the Masquelet technique.
      6.530–70656
      28SA560:401024
      29SA540:60612
      30SA745:55624
      PA: Pseudomona aeruginosa; SA: Staphylococcus aureus; CNS: Coagulase negative staphylococcus; E: Enterorococcus sp; (−): cultive negative; POLI
      • Metsemakers W.J.
      • Fragomen A.T.
      • Moriaty T.F.
      • et al.
      Fracture-Related Infection (FRI) consensus group. Evidence-based recommendations for local antimicrobial strategies and dead space management in fracture-related infection.
      : E. Cloacae + E. Hemanii; Poly
      • Norris B.L.
      • Vanderkarr M.
      • Sparks Ch
      • Chitnis A.S.
      • Ray B.
      • Holy C.E.
      Treatments, cost and healthcare utilization of patients with segmental bone defects.
      : Enterorococcus sp + B. Cereus + aeromona; Poli
      • Masquelet A.C.
      • Fitoussi F.
      • Begue T.
      • Muller G.P.
      Reconstruction of the long bones by the induced membrane and spongy autograft.
      : E. Cloacae + Staphylococcus epidermidis; Poli
      • Masquelet A.C.
      • Begue T.
      The concept of induced membrane for reconstruction of long bone defects.
      : PA + CNS. Allo: auto %: allograft/autograft proportion; Reop infection: reoperation related to infection; Reop instability: reoperation related to mechanical instability; Y: yes; Failure: non-union or bone resorption.
      The median time between stages was nine weeks (range 6–28). The median length of the bone defect was 5 cm (range 3.5–14).
      One patient treated with a retrograde nail for a bone defect in the distal third of the femoral shaft needed augmentation with a locked plate in the second stage. There were no cases where the fixation implanted in the first stage was removed.
      The most frequent allo-autograft proportion used was 50-50 in 12 (40%) cases. Lower ratios were used in 5 (16.67%) and higher in 13 (43.33%) cases. (Table 2).

      1.6 Outcomes

      1.6.1 Bone healing

      The bone healing rate was 93.33% (n = 28), at a median of 7 months (range 3–12). In 27 (90.0%) cases, it was achieved without reoperation (Fig. 2).
      Fig. 2
      Fig. 2Patient number 21. a-b: Radiographs showing an infected non-union of the tibia with nail failure. c-d: AP and L radiographs after the first stage, showing ATB cement-coated nail fixation and space placement. e-f: Radiographs at months 1 and 6 after the second stage, with a 50-50 auto-allograft ratio. g-h: AP and L radiograph 22 months after the second stage, showing bony healing.
      Fig. 2
      Fig. 2Patient number 21. a-b: Radiographs showing an infected non-union of the tibia with nail failure. c-d: AP and L radiographs after the first stage, showing ATB cement-coated nail fixation and space placement. e-f: Radiographs at months 1 and 6 after the second stage, with a 50-50 auto-allograft ratio. g-h: AP and L radiograph 22 months after the second stage, showing bony healing.

      1.6.2 Reoperation rate

      The overall reoperations rate was 13.33% (n = 4), of which 3.33% (n = 1) was related to mechanical instability, and 10.0% (n = 3) was related to infection.

      1.6.3 Reoperations related to instability

      In a metaphyseal-diaphyseal defect of the proximal tibia patient, which had been fixed with a nail, mobility at the defect site was found five months after the second stage. Stability augmentation with a locked plate was performed, achieving bone healing three months later.

      1.6.4 Reoperations related to infection

      In one case, it was necessary to repeat the first stage three weeks after spacer placement due to the persistence of the infection. This case was treated with nail and spacer removal, surgical debridement, reaming, and fixation with an ATB-cement-coated nail.
      Infection recurrence was registered in two patients at months 8 and 15 after the second stage. As bone healing was observed in both cases, they were treated with nail removal, reaming, placement of an ATB-cement-coated nail, and systemic ATB therapy (Fig. 3). Both were able to control the infection until the end of the study.
      Fig. 3
      Fig. 3Patient number 19. a-b: Radiographs showing segmental tibial fracture with a bony defect. c-d-e: Intraoperative images of the first stage showing cement spacer and soft tissue coverage. f-g: Immediate postoperative AP-L radiographs showing nail fixation and cannulated screw for the medial malleolus fracture. h-i: Immediate postoperative AP-L radiographs of the second stage. j-k: AP and L radiographs showing bone healing at 6.5 months. At month 8, the patient experienced a recurrence of infection (see description in text), so an ATB-coated nail was implanted. l-m: Radiograph showing postoperative bone remodeling at 23 months.
      Fig. 3
      Fig. 3Patient number 19. a-b: Radiographs showing segmental tibial fracture with a bony defect. c-d-e: Intraoperative images of the first stage showing cement spacer and soft tissue coverage. f-g: Immediate postoperative AP-L radiographs showing nail fixation and cannulated screw for the medial malleolus fracture. h-i: Immediate postoperative AP-L radiographs of the second stage. j-k: AP and L radiographs showing bone healing at 6.5 months. At month 8, the patient experienced a recurrence of infection (see description in text), so an ATB-coated nail was implanted. l-m: Radiograph showing postoperative bone remodeling at 23 months.

      1.6.5 Failure rate

      The failure rate was 6.67% (n = 2). One patient suffered nail breakage due to non-union 20 months after the second stage. This patient was treated with a larger diameter reamed nail replacement, achieving bone healing eight months after surgery. The second failure was a patient with a femoral defect initially stabilized with a nail. Thirteen months after the second stage (at the time of the study closure), the patient showed no radiological evidence of bone healing. As the infection was controlled and he was walking pain-free with a cane, the patient refused further surgery.

      1.6.6 Follow-up and functional outcomes

      The median follow-up after the second stage was 42 (range 12–85) months. At the end of the study, all patients were walking without pain, and one was using a cane. The median WOMAC score was 75 (range: 55–87).

      2. Discussion

      The main finding of this study was that with definitive fixation in the first stage of the induced membrane technique, we achieved 93.33% of bone healing, with a reoperation rate due to recurrence or lack of infection control of 10.0%.
      We understand that in I-SBD, performing definitive fixation in the first stage may potentially increase the risk of infection recurrence, as reported by Bose et al..
      • Bose D.
      • Kugan R.
      • Stubbs D.
      • McNally M.
      Management of infected nonunion of the long bones by a multidisciplinary team.
      However, consistent with Bauer et al.
      • Bauer T.
      • Klouche S.
      • Grimaud O.
      • Lortat-Jacob A.
      • Hardy P.
      Treatment of infected non-unions of the femur and tibia in a French referral center for complex bone and joint infections: outcomes of 55 patients after 2 to 11 years.
      and based on the outcomes of this study, we believe that if the initial debridement and soft tissue coverage are proper, this risk does not appear to be increased. Comparing the results of the present study with others in which stabilization in the first stage was performed with external fixations, we observed that the rate of reoperations due to infection was similar. Masquelet et al.
      • Masquelet A.C.
      • Fitoussi F.
      • Begue T.
      • Muller G.P.
      Reconstruction of the long bones by the induced membrane and spongy autograft.
      reported an incidence of 14%, while the rate of reoperations due to infection described by Siboni et al.
      • Siboni R.
      • Joseph E.
      • Blasco L.
      • et al.
      Management of septic non-union of the tibia by induced membrane technique. What factors could be improve results?.
      was 21%.
      One of the pioneers in using a nail as definitive fixation in the initial stage of the technique was Apart et al.,
      • Apard T.
      • Bigorre N.
      • Cronier P.
      • Duteille F.
      • Bizot P.
      • Massin P.
      Two-stage reconstruction of post-traumatic segmental tibia bone loss with nailing.
      who reported bone union and infection recurrence rates of 91.6% and 41%, respectively. The authors associated their reoperation rate due to infection with insufficient initial debridement, an issue widely established as one of the main risk factors for recurrence.
      • Simpson A.H.R.W.
      • Deakin M.
      • Latham J.M.
      Chronic osteomyelitis. The effect of the extent of surgical resection on infection-free survival.
      • Mi M.
      • Papakostidis C.
      • Wu X.
      • Giannoudis P.V.
      Mixed results with the Masquelet technique: a fact or a myth?.
      • Masquelet A.C.
      Induced membrane technique: pearls and pitfalls.
      We agree that this could have been the reoperation causes in our series, being more evident in the early repetition of the first stage of the technique. In addition, the use of ATB in the spacer may have masked the infection, leading to late recurrences.
      • Masquelet A.C.
      Induced membrane technique: pearls and pitfalls.
      Recently, Ayouba et al.
      • Ayouba G.
      • Lemonne F.
      • Kombate N.K.
      • Bakriga B.
      • Yaovi Edem J.
      • Andre-Pierre Max U.
      Interest of nailing associated with the Masquelet technique in reconstruction of bone defect.
      reported a series of patients stabilized with nails in the first stage, in which 37.5% had I-SBD. They reported higher percentages than those obtained in our study, with 100% bone healing and no recurrence, highlighting the advantages of rehabilitation and early return to the patient's daily activities.
      • Ayouba G.
      • Lemonne F.
      • Kombate N.K.
      • Bakriga B.
      • Yaovi Edem J.
      • Andre-Pierre Max U.
      Interest of nailing associated with the Masquelet technique in reconstruction of bone defect.
      Regarding the use of locked plates as a definitive fixation in the first stage, Berstein et al.
      • Berstein M.
      • Fragomen A.T.
      • Sabharwal S.
      • Barclay J.
      • Rozbruch S.R.
      Does integrated fixation provide benefit in the reconstruction of post traumatic tibial bone defect?.
      found no significant difference regarding complication rates when comparing patients treated with a combined fixation (external fixator + plate or nail) against patients stabilized with external fixation alone. In another study, Wang et al.
      • Wang X.
      • Wang S.
      • Fu J.
      • Sun D.
      • Shen J.
      • Xie Z.
      Risk factors associated with recurrence of extremity osteomyelitis treated with the induced membrane technique.
      identified plate fixation and the need for several debridements before the second stage as risk factors for the recurrence of infection. Neither of the two cases with plate fixation was revised in our series.
      We agree with the authors mentioned above
      • Apard T.
      • Bigorre N.
      • Cronier P.
      • Duteille F.
      • Bizot P.
      • Massin P.
      Two-stage reconstruction of post-traumatic segmental tibia bone loss with nailing.
      ,
      • Ayouba G.
      • Lemonne F.
      • Kombate N.K.
      • Bakriga B.
      • Yaovi Edem J.
      • Andre-Pierre Max U.
      Interest of nailing associated with the Masquelet technique in reconstruction of bone defect.
      ,
      • Berstein M.
      • Fragomen A.T.
      • Sabharwal S.
      • Barclay J.
      • Rozbruch S.R.
      Does integrated fixation provide benefit in the reconstruction of post traumatic tibial bone defect?.
      that definitive bone stabilization in the first stage offers the possibility of immediate weight-bearing after each stage and avoids the discomfort generated by external fixation, especially in this type of injury, which usually entails long treatment periods. In addition, possible iatrogenic injury to the membrane when removing the temporary fixation would be avoided.
      Another highlight in this study is related to the proportion of allograft used (between 40 and 65%) to fill the bone defect. Traditionally, the use of autograft has been described as completing the remaining volume with allograft (as an expander) in proportions that do not exceed 3:1.
      • Masquelet A.C.
      • Fitoussi F.
      • Begue T.
      • Muller G.P.
      Reconstruction of the long bones by the induced membrane and spongy autograft.
      ,
      • Masquelet A.C.
      • Begue T.
      The concept of induced membrane for reconstruction of long bone defects.
      ,
      • Giannoudis P.V.
      • Faour O.
      • Goff T.
      • Kanakaris N.
      • Dimitriou R.
      Masquelet technique for the treatment of bone defects: tips-tricks and future directions.
      However, Morelli et al.,
      • Morelli I.
      • Drago L.
      • George D.A.
      • Gallazzi E.
      • Scarponi S.
      • Romanó C.L.
      Masquelet technique: myth or reality? A systematic review and meta-analysis.
      in a systematic review and meta-analysis, described the different types of graft, proportions, and combinations used in 17 studies. They highlight that bone union and reoperation rates did not correlate with the types of grafts used. In our opinion, this shows the technique's versatility and the lack of consensus on this issue. Finally, our rate of bone healing was like the ones reported in two recent meta-analyses, in which a rate of 89.7% and 92.35% were informed.
      • Morelli I.
      • Drago L.
      • George D.A.
      • Gallazzi E.
      • Scarponi S.
      • Romanó C.L.
      Masquelet technique: myth or reality? A systematic review and meta-analysis.
      ,
      • Mi M.
      • Papakostidis C.
      • Wu X.
      • Giannoudis P.V.
      Mixed results with the Masquelet technique: a fact or a myth?.
      Therefore, the allograft ratios used in the present study appear to be a realistic alternative.
      We believe our results are based on respecting and following critical concepts in treating these injuries. Such as achieving an infection-free environment, mainly through an aggressive surgical debridement. Also, by providing adequate soft tissue coverage and an optimal biomechanical environment using stable fixation from the first stage. Finally, filling the bone defect with autograft provides cellularity and its properties (osteogenic, osteoinductive, osteoconductive), together with the osteoconduction provided by the allograft. All of this converges on the closed and richly vascularized space inside the membrane, which provides angiogenic and osteoblastic factors that allow the creation of a microenvironment to promote bone healing.
      • Giannoudis P.V.
      • Einhorn T.A.
      • Marsh D.
      Fracture healing: the diamond concept.
      • Miska M.
      • Schmidmaier G.
      Diamond concept for the treatment of nonunions and bone defects.
      • Andrzejowski P.
      • Giannoudis P.V.
      The diamond concept for long bone non-union management.
      The weaknesses of our study are related to its retrospective design and the number of patients. Another weakness is the absence of a control group, which could have provided greater power to our findings. All these difficulties have been hard to avoid due to the complexity present in each patient. Nevertheless, the authors believe this study could contribute to the current knowledge and a better understanding of the technique.

      3. Conclusions

      Treatment of infected segmental bone defects of the femur and tibia with the Masquelet technique appears feasible and effective. Definitive fixation in the first stage showed a success rate of 93.33%, with a reoperation rate of 10.0% related to infection, confirming the already reported versatility of the technique.

      Funding

      This research did not receive any specific grant from funding agencies in the public, commercial or not-profit sectors.

      Ethics

      This retrospective chart review study, involving human participants, was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments. The Bioethics Committee of British Hospital of Buenos Aires approved this study (Protocol number 7517).

      Consent to participate

      Informed consent was obtained from all individual participants included in the study.

      Availability of data and material

      All data generated and analyzed during this study are included in this published article and are available from the corresponding author on reasonable request.

      Authors ‘contributions

      Germán Garabano and Cesar Pesciallo contributed to the study conception and design. Material preparation, data collection and analysis were performed by Germán Garabano. The first draft of the manuscript was written by German Garabano and Cesar Pesciallo commented on previous versions of the manuscript. Both authors read and approved the final manuscript.

      Declaration of competing interest

      None.

      Acknowledgments

      none.

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