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Abundant heterotopic bone formation following use of rhBMP-2 in the treatment of acetabular bone defects during revision hip arthroplasty

Open AccessPublished:January 12, 2018DOI:https://doi.org/10.1016/j.artd.2017.12.004

      Abstract

      Revision hip arthroplasty in the setting of periacetabular bone loss presents a significant challenge, as options for restoring bone loss are limited. Recombinant human bone morphogenetic protein-2 may offer a solution by promoting bone growth to restore bone stock before implant reimplantation. Here we present a case of a patient with a periprosthetic acetabulum fracture, resulting in pelvic discontinuity as the result of significant periacetabular bone loss. Using a staged approach, periacetabular bone stock was nearly entirely reconstituted using recombinant BMPs and allograft, which resulted in stable fixation, but with abundant heterotopic bone formation. Recombinant BMP-2 offers a useful tool for restoring bone stock in complex hip arthroplasty revision cases with periacetabular bone loss; however, caution must be used as overabundant bone growth as heterotopic ossification may result.

      Keywords

      Introduction

      Periacetabular bone loss in revision hip arthroplasty presents a significant challenge, with limited options for reconstruction. Here we present a case where recombinant human bone morphogenetic protein (rhBMP)-2 was utilized to promote bone reconstitution, however was associated with abundant heterotopic ossification.

      Case history

      A 42-year-old woman with rheumatoid arthritis on prednisone presented to the emergency department with severe right hip pain and inability to bear weight after sustaining a twisting injury while stepping off a curb. She previously had a right total hip arthroplasty performed 20 years ago and revised 1 year prior for loosening. She reported never having a pain-free interval after her revision. Physical examination revealed significant pain with any right hip range of motion and inability to perform active straight leg raise. Radiographs revealed a right transverse periprosthetic acetabulum fracture with an acetabular component that was grossly loose and protruded. Extensive osteolysis and bone loss were noted in both the ischium and ilium (Fig. 1). Laboratory workup at that time yielded erythrocyte sedimentation rate and C-reactive protein levels that were within normal limits. Hip aspiration was also performed, which was negative for infection.
      Figure thumbnail gr1
      Figure 1Preoperative pelvic radiographs. Anteroposterior (AP) (a), inlet (b), outlet (c), obturator oblique (d), and iliac oblique (e) images.
      After discussion with the patient, the decision was made to proceed with acetabular component revision for aseptic loosening. Prednisone was held before her surgery. At the time of surgery, she was found to have a grossly loose acetabular component with a complex pelvic discontinuity involving transverse fractures through the anterior and posterior columns as well as a large segmental posterior wall fragment. There was significant osteolysis, which precluded stable fixation of an immediate revision acetabular component. The decision was made to perform the revision in a staged fashion because the extent of bone loss would have limited bony contact (<30%) with the implant as well as insufficient screw fixation. In addition, there was concern for the ability to achieve bony union of the discontinuity, given her history of rheumatoid arthritis. A 2.8-cc dose of rhBMP-2 and 10 mL of demineralized bone matrix were placed overlying the discontinuity site and 150 cc of allograft bone chips within the acetabulum. The femoral component was retained. (Fig. 2) She remained toe-touch weight-bearing postoperatively.
      Figure thumbnail gr2
      Figure 2Postoperative radiograph taken immediately after the first staged surgery.
      The patient underwent the second stage of her revision 7 months later.
      Intraoperatively, she was found to have completely healed the pelvic discontinuity with reconstitution of the entire acetabulum with restoration of the anterior and posterior columns as well as dome and medial wall. Furthermore, an abundance of heterotopic ossification (HO) had also formed around the acetabulum, which was excised. (Fig. 3) An acetabular component with trabecular metal augments and 5 screws for fixation were placed and supplemented with autograft from the excised HO. (Fig. 4)
      Figure thumbnail gr3
      Figure 3Two months after explant and bone grafting postoperative radiographs of the pelvis (a), hip AP (b), and lateral (c).
      Figure thumbnail gr4
      Figure 4Radiographs taken after the second stage of the procedure. Immediately postoperative (a), 8 months postoperative AP pelvis (b), AP hip (c), and lateral hip (d).
      The patient had an uneventful perioperative recovery and was discharged from the hospital. By 4 months postoperatively, her pain had nearly resolved, incisions were healed, and radiographs demonstrated early osteointegration of the acetabular augment and implant. At 2-year follow-up, she was doing very well without pain and walking without limp.

      Discussion

      Basic science

      Bone morphogenetic proteins (BMPs) were discovered in 1965 when implantation of demineralized bone matrix led to new bone formation, suggesting unknown local factors resulted in osteogenesis by autoinduction [
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      ]. BMPs are now understood to be members of the TGF-β supergene family and play a crucial role in the differentiation of the osteogenic lineage and fracture repair [
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      ]. Osteogenic BMPs, particularly BMP-2 and BMP-7, function through tyrosine-kinase receptors to activate the Smad protein-signaling pathway (Fig. 5). This, in-turn, activates gene transcription factors to differentiate mesenchymal cells into osteogenic and chondrogenic phenotypes [
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      ]. Induced bone formation occurs because a chemical gradient leads to chemotaxis of chondrogenic and osteogenic cells, followed by vascular invasion and cell differentiation [
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      ,
      • Wang E.A.
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      ]. In addition to its primary function in regulating bone tissues, the BMP cascade also functions to regulate cell growth, movement, and homeostasis [
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      • Wozney J.M.
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      ]. During fracture healing, BMP subtype expression occurs in a specific temporal fashion to regulate cartilage calcification and osteoblast recruitment [
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      Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing.
      ].
      Two BMP subtypes have been approved by the US Food and Drug administration (FDA) for clinical use in humans: rhBMP-7 (also known as osteogenic protein-1, initially distributed by Stryker Biotech, Hopkinton, MA, but now not available in the United States) and rhBMP-2 (INFUSE, Medtronic, Inc. Fridley, MN) []. rhBMP-2 is approved by the US FDA for 3 specific indications: 1. Treatment of lumbar interbody fusion using metallic cage, rhBMP-2, and collagen sponge carrier; 2. Treatment of open tibial shaft fractures treated with intramedullary nail fixation; and 3. As an alternative to autogenous bone graft for sinus augmentation and localized alveolar ridge augmentation for defects associated with extraction sockets.
      Multiple animal studies have demonstrated that rhBMP-2 leads to local bone and cartilage formation [
      • Wang E.A.
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      • et al.
      Recombinant human bone morphogenetic protein induces bone formation.
      ] and has a time- and dosage-dependent effect to accelerate cartilage formation and bone mineralization [
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      ,
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      • Rossini G.
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      Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in cultures of fetal rat calvarial osteoblasts.
      ]. BMPs improve bony ingrowth into porous metal implants and lead to more rapid initial callus formation, maturation, and greater early torsional strength in animal models [
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      • Okada T.
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      • Bouxsein M.L.
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      ,
      • Li R.H.
      • Bouxsein M.L.
      • Blake C.A.
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      rhBMP-2 injected in a calcium phosphate paste (alpha-BSM) accelerates healing in the rabbit ulnar osteotomy model.
      ].

      Clinical utilization of BMPs

      Advantages of BMPs include the potential to achieve similar union rates as cancellous autograft but with decreased rates of donor site pain [
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      ]. In the spine literature, initial reports found that BMPs provide comparable posterolateral fusion rates as local autograft [
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      • Aspenberg P.
      Randomized radiostereometric study comparing osteogenic protein-1 (BMP-7) and autograft bone in human noninstrumented posterolateral lumbar fusion: 2002 Volvo Award in clinical studies.
      ,
      • Vaccaro A.R.
      • Patel T.
      • Fischgrund J.
      • et al.
      A pilot study evaluating the safety and efficacy of OP-1 Putty (rhBMP-7) as a replacement for iliac crest autograft in posterolateral lumbar arthrodesis for degenerative spondylolisthesis.
      ,
      • Vaccaro A.R.
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      • et al.
      A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions.
      ,
      • Delawi D.
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      • et al.
      A prospective, randomized, controlled, multicenter study of osteogenic protein-1 in instrumented posterolateral fusions: report on safety and feasibility.
      ,
      • Dawson E.
      • Bae H.W.
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      • Stambough J.L.
      • Glassman S.D.
      Recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge with an osteoconductive bulking agent in posterolateral arthrodesis with instrumentation. A prospective randomized trial.
      ]. A randomized study by Hurlbert et al [
      • Hurlbert R.J.
      • Alexander D.
      • Bailey S.
      • et al.
      rhBMP-2 for posterolateral instrumented lumbar fusion: a multicenter prospective randomized controlled trial.
      ] found that patients receiving rhBMP-2 demonstrated a higher rate of radiographic fusion than those who received autograft, but found no differences in clinical outcomes. Michielsen et al [
      • Michielsen J.
      • Sys J.
      • Rigaux A.
      • Bertrand C.
      The effect of recombinant human bone morphogenetic protein-2 in single-level posterior lumbar interbody arthrodesis.
      ] found analogous fusion rates in patients receiving either rhBMP-2 or autologous iliac crest graft. In the trauma literature, Govender et al [
      • Govender S.
      • Csimma C.
      • Genant H.K.
      • et al.
      Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients.
      ] randomized 450 patients with open tibia fractures to intramedullary nail fixation with or without rhBMP-2. Though patients who received high-dose rhBMP-2 required fewer secondary interventions and demonstrated accelerated fracture healing, intramedullary reaming was also performed more frequently in the BMP group. In patients treated with reamed intramedullary nails for open tibial shaft fractures. Lyon et al [
      • Lyon T.
      • Scheele W.
      • Bhandari M.
      • et al.
      Efficacy and safety of recombinant human bone morphogenetic protein-2/calcium phosphate matrix for closed tibial diaphyseal fracture: a double-blind, randomized, controlled phase-II/III trial.
      ] randomized patients with closed tibial shaft fractures to reamed, locked intramedullary nails with or without rhBMP-2. No differences in infection rates, time to radiographic union or pain-free weight-bearing was noted; however, patients receiving rhBMP-2 had increased rates of venous thromboembolism and postoperative HO.
      As the clinical usage of BMPs has increased, its safety has been called into question [
      • Fu R.
      • Selph S.
      • McDonagh M.
      • et al.
      Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis.
      ,
      • Rodgers M.A.
      • Brown J.V.
      • Heirs M.K.
      • et al.
      Reporting of industry funded study outcome data: comparison of confidential and published data on the safety and effectiveness of rhBMP-2 for spinal fusion.
      ]. Carragee et al initially reported concerns, pointing out that many initial trials were sponsored by industry and may have under-reported adverse events [
      • Jones A.L.
      • Bucholz R.W.
      • Bosse M.J.
      • et al.
      Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized, controlled trial.
      ,
      • Rodgers M.A.
      • Brown J.V.
      • Heirs M.K.
      • et al.
      Reporting of industry funded study outcome data: comparison of confidential and published data on the safety and effectiveness of rhBMP-2 for spinal fusion.
      ,
      • Chen Z.
      • Ba G.
      • Shen T.
      • Fu Q.
      Recombinant human bone morphogenetic protein-2 versus autogenous iliac crest bone graft for lumbar fusion: a meta-analysis of ten randomized controlled trials.
      ,
      • Carragee E.J.
      • Hurwitz E.L.
      • Weiner B.K.
      A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned.
      ]. In some studies, BMPs have shown no advantages over autograft and may lead to greater risk of complications such as osteolysis and bony resorption, ectopic bone formation, retrograde ejaculation, wound complications, life-threatening cervical soft-tissue swelling, and nerve root radiculitis [
      • Carragee E.J.
      • Hurwitz E.L.
      • Weiner B.K.
      A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned.
      ,
      • Villavicencio A.T.
      • Burneikiene S.
      • Nelson E.L.
      • Bulsara K.R.
      • Favors M.
      • Thramann J.
      Safety of transforaminal lumbar interbody fusion and intervertebral recombinant human bone morphogenetic protein-2.
      ,
      • Vaidya R.
      • Sethi A.
      • Bartol S.
      • Jacobson M.
      • Coe C.
      • Craig J.G.
      Complications in the use of rhBMP-2 in PEEK cages for interbody spinal fusions.
      ,
      • Simmonds M.C.
      • Brown J.V.
      • Heirs M.K.
      • et al.
      Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data.
      ]. Caution should be taken during placement of BMPs because displacement or migration has led to ectopic bone formation, which can potentially affect nearby critical structures [
      • Poynton A.R.
      • Lane J.M.
      Safety profile for the clinical use of bone morphogenetic proteins in the spine.
      ]. Through December 2011, the FDA received 62 reports of adverse events following rhBMP-2 use in nonspinal applications, including wound complications, HO formation, and local inflammation [
      • Woo E.J.
      Adverse events after recombinant human BMP2 in nonspinal orthopaedic procedures.
      ].
      Though concerns of BMPs as a pro-oncogenic protein have been raised, a large study using the Medicare database found no increased risk of malignancy [
      • Kelly M.P.
      • Savage J.W.
      • Bentzen S.M.
      • Hsu W.K.
      • Ellison S.A.
      • Anderson P.A.
      Cancer risk from bone morphogenetic protein exposure in spinal arthrodesis.
      ].
      BMPs have been studied in the treatment of acetabular bone defects due to osteolysis, as the alternatives of bone allograft or autograft have not reliably produced bony ingrowth in a porous implant [
      • Cook S.D.
      • Barrack R.L.
      • Patron L.P.
      • Salkeld S.L.
      Osteoinductive agents in reconstructive hip surgery: a look forward.
      ,
      • Søballe K.
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      • Pedersen C.M.
      • Bünger C.
      Bone graft incorporation around titanium-alloy- and hydroxyapatite-coated implants in dogs.
      ]. Bragdon et al implanted porous-coated titanium acetabular components after creating central acetabular defects in a canine model. Those receiving rhBMP-2 had near-complete bony bridging, whereas defects in the control group remained empty with fibrous tissue [
      • Bragdon C.R.
      • Doherty A.M.
      • Rubash H.E.
      • et al.
      The efficacy of BMP-2 to induce bone ingrowth in a total hip replacement model.
      ]. Hoshino et al [
      • Hoshino M.
      • Namikawa T.
      • Kato M.
      • Terai H.
      • Taguchi S.
      • Takaoka K.
      Repair of bone defects in revision hip arthroplasty by implantation of a new bone-inducing material comprised of recombinant human BMP-2, Beta-TCP powder, and a biodegradable polymer: an experimental study in dogs.
      ] performed total hip arthroplasty after creating proximal femur and acetabular defects in a canine model. Hips receiving rhBMP-2 demonstrated complete radiographic healing of both femoral and acetabular defects, as compared to none in groups receiving carrier only. Histologic examination of hips receiving rhBMP-2 demonstrated bony ingrowth of woven bone and fibrous tissue compared to minimal ingrowth and persistent bony defect in the control group. Barrack et al [
      • Barrack R.L.
      • Cook S.D.
      • Patrón L.P.
      • Salkeld S.L.
      • Szuszczewicz E.
      • Whitecloud T.S.
      Induction of bone ingrowth from acetabular defects to a porous surface with OP-1.
      ] created central acetabular defects in a canine model and performed porous-coated titanium total hip arthroplasties. Hips treated with rhBMP-7 had more complete radiographic bony healing, greater histologic new bone formation, and increased ingrowth into the porous metal implant. Hips receiving rhBMP-7 had even greater bony ingrowth into the implant than hips treated without an acetabular defect. Jensen et al found the addition of rhBMP-7 increased bone formation and mechanical stability of a hydroxyapatite-coated implant in a canine model [
      • Jensen T.B.
      • Overgaard S.
      • Lind M.
      • Rahbek O.
      • Bünger C.
      • Søballe K.
      Osteogenic protein 1 device increases bone formation and bone graft resorption around cementless implants.
      ,
      • Jensen T.B.
      • Overgaard S.
      • Lind M.
      • Rahbek O.
      • Bünger C.
      • Søballe K.
      Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute: an experimental study in dogs.
      ].
      Cook et al reported a clinical case where rhBMP-7 was used with femoral head allograft to successfully reconstruct a large acetabular defect [
      • Cook S.D.
      • Barrack R.L.
      • Santman M.
      • Patron L.P.
      • Salkeld S.L.
      • Whitecloud T.S.
      The Otto Aufranc Award. Strut allograft healing to the femur with recombinant human osteogenic protein-1.
      ,
      • Cook S.D.
      • Barrack R.L.
      • Shimmin A.
      • Morgan D.
      • Carvajal J.P.
      The use of osteogenic protein-1 in reconstructive surgery of the hip.
      ]. Similarly, Jager et al reported the successful usage of rhBMP-2 in a staged fashion to bridge a large acetabular defect [
      • Jäger M.
      • Emami R.
      • Thorey F.
      • Krauspe R.
      Saving implants BMP-2 application in revision total hip surgery.
      ]. Kärrholm et al [
      • Kärrholm J.
      • Hourigan P.
      • Timperley J.
      • Razaznejad R.
      Mixing bone graft with OP-1 does not improve cup or stem fixation in revision surgery of the hip: 5-year follow-up of 10 acetabular and 11 femoral study cases and 40 control cases.
      ] published a retrospective case–control series investigating the use of rhBMP-7 for bone loss in acetabular revision. Impaction grafting using morselized femoral head allograft in conjunction with 3.5 mg of rhBMP-7 was performed. Control cases were matched for age, gender, type of defect, type of implant, and volume of allograft used. The authors found no differences in Harris hip score or reported pain between groups, but 2 patients in the BMP group required acetabular revision for loosening and proximal component migration.

      Heterotopic ossification

      We present a case where the therapeutic use of recombinant BMPs was associated with HO [
      • Kaplan F.S.
      • Glaser D.L.
      • Hebela N.
      • Shore E.M.
      Heterotopic ossification.
      ,
      • O'Connor J.P.
      Animal models of heterotopic ossification.
      ]. Conditions such as fibrodysplasia ossificans progressiva, where mRNA expression of BMP-4 is upregulated, and progressive osseous heteroplasia have shed light on the pathways for ectopic bone formation [
      • Shafritz A.B.
      • Shore E.M.
      • Gannon F.H.
      • et al.
      Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva.
      ,
      • Shore E.M.
      • Glaser D.L.
      • Gannon F.H.
      Osteogenic induction in hereditary disorders of heterotopic ossification.
      ]. Current animal models of HO are based on the surgical implantation of BMPs, which induce heterotopic bone formation through endochondral ossification. rhBMP has been shown to create ectopic bone when implanted in subcutaneous tissue in a dose-dependent fashion [
      • Wang E.A.
      • Rosen V.
      • D'Alessandro J.S.
      • et al.
      Recombinant human bone morphogenetic protein induces bone formation.
      ,
      • Love D.A.
      • Lietman S.A.
      The effect of osteogenic protein-1 dosing regimen on ectopic bone formation.
      ,
      • Sampath T.K.
      • Maliakal J.C.
      • Hauschka P.V.
      • et al.
      Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro.
      ]. Though the exact mechanism of HO remains unknown, 3 key phases for its development have been identified: 1. Inductive signaling pathways, 2. Inducible osteoprogenitor cells, and 3. A microenvironment conducive to osteogenesis [
      • Kaplan F.S.
      • Glaser D.L.
      • Hebela N.
      • Shore E.M.
      Heterotopic ossification.
      ].
      Rates of significant HO formation following total hip arthroplasty ranges from 1% to 27% and is associated with male gender, advanced patient age, increased soft-tissue trauma, and hematoma formation [
      • Ahrengart L.
      Periarticular heterotopic ossification after total hip arthroplasty. Risk factors and consequences.
      ,
      • Tannous O.
      • Stall A.C.
      • Griffith C.
      • Donaldson C.T.
      • Castellani R.J.
      • Pellegrini V.D.
      Heterotopic bone formation about the hip undergoes endochondral ossification: a rabbit model.
      ,
      • Board T.N.
      • Karva A.
      • Board R.E.
      • Gambhir A.K.
      • Porter M.L.
      The prophylaxis and treatment of heterotopic ossification following lower limb arthroplasty.
      ]. Fracture morphology, early timing of surgery, and associated abdominal and thoracic injuries correlate with the development of heterotopic bone formation following acetabular surgery [
      • Ghalambor N.
      • Matta J.M.
      • Bernstein L.
      Heterotopic ossification following operative treatment of acetabular fracture. An analysis of risk factors.
      ,
      • Chémaly O.
      • Hebert-Davies J.
      • Rouleau D.M.
      • Benoit B.
      • Laflamme G.Y.
      Heterotopic ossification following total hip replacement for acetabular fractures.
      ]. Both nonsteroidal anti-inflammatory medications and perioperative radiation therapy have been used for HO prophylaxis following major hip surgery; randomized trials have shown both to be effective [
      • Board T.N.
      • Karva A.
      • Board R.E.
      • Gambhir A.K.
      • Porter M.L.
      The prophylaxis and treatment of heterotopic ossification following lower limb arthroplasty.
      ,
      • Moore K.D.
      • Goss K.
      • Anglen J.O.
      Indomethacin versus radiation therapy for prophylaxis against heterotopic ossification in acetabular fractures: a randomised, prospective study.
      ,
      • Burd T.A.
      • Lowry K.J.
      • Anglen J.O.
      Indomethacin compared with localized irradiation for the prevention of heterotopic ossification following surgical treatment of acetabular fractures.
      ,
      • Schneider D.J.
      • Moulton M.J.
      • Singapuri K.
      • et al.
      The Frank Stinchfield Award. Inhibition of heterotopic ossification with radiation therapy in an animal model.
      ]. Though some reviews contend radiation as superior [
      • Blokhuis T.J.
      • Frölke J.P.
      Is radiation superior to indomethacin to prevent heterotopic ossification in acetabular fractures?: a systematic review.
      ], a recent meta-analysis of more than 1200 patients found similar efficacy between the 2 treatment modalities in preventing heterotopic bone formation [
      • Vavken P.
      • Castellani L.
      • Sculco T.P.
      Prophylaxis of heterotopic ossification of the hip: systematic review and meta-analysis.
      ]. Patient compliance in completing 6 weeks of nonsteroidal anti-inflammatory medication prophylaxis are thought to contribute to differences seen between the 2 treatment methods [
      • Vielpeau C.
      • Joubert J.M.
      • Hulet C.
      Naproxen in the prevention of heterotopic ossification after total hip replacement.
      ,
      • Gebuhr P.
      • Soelberg M.
      • Orsnes T.
      • Wilbek H.
      Naproxen prevention of heterotopic ossification after hip arthroplasty. A prospective control study of 55 patients.
      ].
      Other reports have been published describing heterotopic bone formation following the therapeutic use of rhBMPs. In a randomized trial, Haid et al reported that the use of rhBMP-2 in lumbar interbody cages was associated with new bone formation into the spinal canal or neuroforamina in 71% patients [
      • McKay B.
      • Sandhu H.S.
      Use of recombinant human bone morphogenetic protein-2 in spinal fusion applications.
      ,
      • Haid R.W.
      • Branch C.L.
      • Alexander J.T.
      • Burkus J.K.
      Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages.
      ]. Wysocki and Cohen reported pathologic bone formation in the triceps musculature following rhBMP-7 use when treating a distal humerus fracture nonunion [
      • Wysocki R.W.
      • Cohen M.S.
      Ectopic ossification of the triceps muscle after application of bone morphogenetic protein-7 to the distal humerus for recalcitrant nonunion: a case report.
      ]. Axelrad et al reported 4 cases of substantial heterotopic bone formation in the upper extremity following the use of rhBMPs for fractures [
      • Axelrad T.W.
      • Steen B.
      • Lowenberg D.W.
      • Creevy W.R.
      • Einhorn T.A.
      Heterotopic ossification after the use of commercially available recombinant human bone morphogenetic proteins in four patients.
      ]. Boraiah et al reported heterotopic bone formation in 59% of patients when rhBMP-2 was used during surgical treatment of acute tibial plateau fractures [
      • Boraiah S.
      • Paul O.
      • Hawkes D.
      • Wickham M.
      • Lorich D.G.
      Complications of recombinant human BMP-2 for treating complex tibial plateau fractures: a preliminary report.
      ].

      Summary

      Management of periacetabular bone loss presents a challenge during total hip arthroplasty; we present a case of staged acetabular revision using recombinant BMPs and allograft to effectively restore bone stock, followed by implantation of an acetabular component with trabecular metal augments, leading to stable fixation and satisfactory clinical results at 1 year postoperatively. However, abundant heterotopic bone formation was noted within the soft tissues around the hip after the first stage and thus we urge caution when using recombinant BMPs in this application.

      Appendix A. Supplementary data

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