Ramly Elie P, Alfonso Allyson R, Kantar Rami S, Wang Maxime M, Siso J Rodrigo Diaz, Ibrahim Amel, Coelho Paulo G, Flores Roberto L
Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, N.Y.
Plast Reconstr Surg Glob Open. 2019 Aug 19;7(8):e2347. doi: 10.1097/GOX.0000000000002347. eCollection 2019 Aug.
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.
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.
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.
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.
重组人骨形态发生蛋白-2（rhBMP-2）是颅面骨骼中最常用的成骨剂之一。本研究回顾了rhBMP-2应用于颅面重建的安全性和有效性，并评估了当前可用的科学证据水平。
进行了广泛的文献检索。对英文随机对照试验（RCT）、病例系列和报告以及美国食品药品监督管理局的报告进行了综述。使用牛津循证医学中心证据水平量表对研究进行分级。数据异质性排除了定量分析。
确定了17项RCT（证据水平：Ib-IIb），评估rhBMP-2在上颌窦、牙槽嵴、牙槽裂或颅骨缺损重建中的应用（样本量：7-160；年龄：8-75岁）。研究设计的严谨程度各不相同，随访时间为3-36个月，结果评估依赖于临床检查、放射学和/或组织学。rhBMP-2的浓度、载体和对照存在很大差异。大多数评估rhBMP-2用于颅骨缺损闭合、下颌骨重建或牵张成骨的研究包括回顾性队列研究和病例报告。证据不支持rhBMP-2用于上颌窦壁增厚、颅骨重建、下颌骨重建或牵张成骨。rhBMP-2可能对成人牙槽重建有效，但与术后水肿增加有关。
在整形和重建手术的大多数应用中，rhBMP-2相对于替代替代品的风险效益比仍有待证明。缺乏关于颅面生长的长期数据，在18岁以下患者中使用rhBMP-2仍属于超说明书用药。
