Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Craniofacial Surgery

Abstract

Introduction:Recombinant human bone morphogenetic protein-2 (rhBMP-2) is one of the most commonly used osteogenic agents in the craniofacial skeleton. This study reviews the safety and efficacy of rhBMP-2 as applied to craniofacial reconstruction and assesses the level of scientific evidence currently available.Methods:An extensive literature search was conducted. Randomized controlled trials (RCTs), case series and reports in the English language as well as Food and Drug Administration reports were reviewed. Studies were graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence Scale. Data heterogeneity precluded quantitative analysis.Results:Seventeen RCTs (Levels of evidence: Ib-IIb) were identified evaluating the use of rhBMP-2 in maxillary sinus, alveolar ridge, alveolar cleft, or cranial defect reconstruction (sample size: 7–160; age: 8–75 years). Study designs varied in rigor, with follow-up ranging 3–36 months, and outcome assessment relying on clinical exam, radiology, and/or histology. There was wide variation in rhBMP-2 concentrations, carriers, and controls. Most studies evaluating rhBMP-2 for cranial defect closure, mandibular reconstruction, or distraction osteogenesis consisted of retrospective cohorts and case reports. The evidence fails to support RhBMP-2 use in maxillary sinus wall augmentation, calvarial reconstruction, mandibular reconstruction, or distraction osteogenesis. RhBMP-2 may be effective in alveolar reconstruction in adults, but is associated with increased postoperative edema.Conclusions:A risk–benefit ratio favoring rhBMP-2 over alternative substitutes remains to be demonstrated for most applications in plastic and reconstructive surgery. Long-term data on craniofacial growth is lacking, and using rhBMP-2 in patients younger than 18 years remains off-label.

Is Reconstruction of Large Mandibular Defects Using Bioengineering Materials Effective?

“…16,17 A tissueengineered composite graft is an excellent costefficient, alternative reconstructive approach that is efficient, decreases the length of the operation and inpatient stay, eliminates the risks and perioperative complications of the aforementioned procedures, and adequately fulfills the core principles of osseous regeneration (ie, osteogenesis, osteoinduction, osteoconduction). 9 Immediate reconstruction of the mandibular defect was our preferred approach for most of our patients (22 of 34) owing to the efficiency, decreased resources required, decreased time for the patients under general anesthesia, and consideration of our patients' preferences. Nevertheless, secondary reconstruction was selected for existing defects or if extensive loss of soft tissue occurred or was expected (12 of 34).…”

“…8 Allogeneic bone in particulate form can be used as a biologic scaffold, and recombinant human bone morphogenic protein-2 (rhBMP-2) is used to provide the required signaling agents and supporting growth factors. 9 The composite tissue-engineered graft, although used sparingly in the past, is now a mainstay in the reconstruction of maxillomandibular continuity defects resulting from benign pathologic ablation or trauma at our institution (Department of Oral and Maxillofacial Surgery, University of Texas Health Science Center at Houston).…”

Comparison of Bone Regeneration in Different Forms of Bovine Bone Scaffolds with Recombinant Human Bone Morphogenetic Protein-2

“…Various combinations of rhBMP-2 and scaffolds have been used for alveolar bone reconstruction. Although the development of postoperative edema is a significant concern when using a relatively high concentration of rhBMP-2, it shows favorable results in bone formation and efficacy as an osteogenic agent [18].…”

Existing Bone-Derived Bone Morphogenetic Protein-2 Initiates Contact Osteogenesis on the Surface of a Titanium Implant

“…In 2004, rhBMP-7 received limited approval from the FDA under a Humanitarian Device Exemption, but in 2009, it failed to gain FDA Premarket Approval. As a result, only a rhBMP-2 product on the market is approved for clinical use today [19][20][21] .…”