Krishnakumar Gopal Shankar, Roffi Alice, Reale Davide, Kon Elizaveta, Filardo Giuseppe
Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy.
I Orthopaedic and Traumatologic Clinic, Rizzoli Orthopaedic Institute, Via Pupilli 1, 40136, Bologna, Italy.
Int Orthop. 2017 Jun;41(6):1073-1083. doi: 10.1007/s00264-017-3471-9. Epub 2017 Apr 19.
This paper documents the existing evidence on bone morphogenetic proteins (BMPs) use for the treatment of bone fractures, non-union, and osteonecrosis, through a review of the clinical literature, underlying potential and limitations in terms of cost effectiveness and risk of complications.
A systematic review was performed on the PubMed database using the following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone regeneration) including papers from 2000 to 2016. The search focused on clinical trials dealing with BMPs application to favor bone regeneration in bone fractures, non-union, and osteonecrosis, in English language, with level of evidence I, II, III, and IV. Relevant data (type of study, number of patients, BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were extracted and analyzed.
Forty-four articles met the inclusion criteria: 10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series, and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures, and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found among RCTs and comparative papers: 11 reported positive results for BMPs augmentation, 3 obtained no significant effects, and 2 showed negative results. The only study comparing the two BMPs showed a better outcome with rhBMP-2 for non-union treatment.
Clinical evidence on BMPs use for the treatment of fractures, non-union, and osteonecrosis is still controversial, with the few available reports being mainly of low quality. While positive findings have been described in many studies, mixed results are still present in the literature in terms of efficacy and adverse events. The difficulties in drawing clear conclusions are also due to the studies heterogeneity, mainly in terms of different BMPs applied, with different concomitant treatments for each bone pathology. Therefore, further research with well-designed studies is needed in order to understand the real potential of this biological approach to favour bone healing.
本文通过回顾临床文献，记录了关于骨形态发生蛋白（BMPs）用于治疗骨折、骨不连和骨坏死的现有证据，以及在成本效益和并发症风险方面的潜在优势和局限性。
在PubMed数据库上进行了一项系统综述，使用以下检索词：（骨形态发生蛋白或BMPs）和（骨修复或骨再生），纳入2000年至2016年的论文。检索重点是关于BMPs应用于促进骨折、骨不连和骨坏死中骨再生的临床试验，文献语言为英语，证据等级为I、II、III和IV。提取并分析相关数据（研究类型、患者数量、BMPs递送材料、剂量、部位、随访、结果和不良事件）。
44篇文章符合纳入标准：10项随机对照试验（RCTs）、7项比较研究、18个病例系列和9个病例报告。rhBMP-2主要用于治疗骨折，rhBMP-7主要用于治疗骨不连和骨坏死。在RCTs和比较性论文中发现了混合结果：11篇报告了BMPs增强治疗的阳性结果，3篇未获得显著效果，2篇显示阴性结果。唯一一项比较两种BMPs的研究表明，rhBMP-2治疗骨不连的效果更好。
关于BMPs用于治疗骨折、骨不连和骨坏死的临床证据仍存在争议，现有的少数报告质量大多较低。虽然许多研究描述了阳性结果，但在疗效和不良事件方面，文献中仍存在混合结果。难以得出明确结论的原因还在于研究的异质性，主要体现在应用的BMPs不同，以及针对每种骨病理的伴随治疗不同。因此，需要进行设计良好的进一步研究，以了解这种生物方法促进骨愈合的真正潜力。
