Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.
Laboratory for Mineralized Tissues, Centre for Translational and Clinical Research, University of Zagreb School of Medicine, Zagreb, Croatia.
J Bone Miner Res. 2020 Oct;35(10):1893-1903. doi: 10.1002/jbmr.4107. Epub 2020 Jul 2.
Bone morphogenetic proteins (BMPs) are potent osteogenic proteins that induce new bone formation in vivo. However, their effect on bone healing in the trabecular bone surfaces remains challenging. We evaluated the safety and efficacy of recombinant human BMP6 (rhBMP6) applied within an autologous blood coagulum (ABC) in a surgically created wedge defect of the proximal tibia in patients undergoing high tibial osteotomy (HTO) for varus deformity and medial osteoarthritis of the knee. We enrolled 20 HTO patients in a randomized, placebo-controlled, double-blinded phase I/II clinical trial. RhBMP6/ABC (1.0 mg/10 mL ABC prepared from peripheral blood) or placebo (10 mL ABC containing excipients) was administered into the tibial wedge defects. Patients were followed for 0 to 24 months by clinical examination (safety) and computed tomography (CT) and serial radiographic analyses (efficacy). The results show that there were no detectable anti-rhBMP6 antibodies in the blood of any of the 20 patients at 14 weeks after implantation. During the 24 months of follow-up, there were no serious adverse reactions recorded. The CT scans from defects of patients treated with rhBMP6/ABC showed an accelerated bone healing compared with placebo at 9 weeks (47.8 ± 24.1 versus 22.2 ± 12.3 mg/cm ; p = 0.008) and at 14 weeks (89.7 ± 29.1 versus 53.6 ± 21.9 mg/cm ; p = 0.006) follow-up. Radiographic analyses at weeks 6 and 24 and months 12 and 24 suggested the advanced bone formation and remodeling in rhBMP6/ABC-treated patients. In conclusion, we show that rhBMP6/ABC at a dose of 100 μg/mL accelerated bone healing in patients undergoing HTO without serious adverse events and with a good tolerability compared with placebo alone. Overall, for the first time, a BMP-based osteogenic implant was examined against a placebo for bone healing efficacy in the trabecular bone surface, using an objective bone mineral density measurement system. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
骨形态发生蛋白（BMPs）是一种有效的成骨蛋白，能在体内诱导新骨形成。然而，其在小梁骨表面的骨愈合效果仍然具有挑战性。我们评估了在接受高位胫骨截骨术（HTO）治疗内翻畸形和膝关节内侧骨关节炎的患者中，将重组人 BMP6（rhBMP6）应用于自体血凝块（ABC）中的安全性和有效性。我们在一项随机、安慰剂对照、双盲的 I/II 期临床试验中招募了 20 名 HTO 患者。rhBMP6/ABC（由外周血制备的 1.0mg/10mL ABC）或安慰剂（10mL ABC 含赋形剂）被注入胫骨楔形缺损中。通过临床检查（安全性）和计算机断层扫描（CT）和连续的影像学分析（疗效）对患者进行 0 至 24 个月的随访。结果显示，在植入后 14 周，20 名患者的血液中均未检测到可检测的抗 rhBMP6 抗体。在 24 个月的随访期间，未记录到严重的不良反应。rhBMP6/ABC 治疗的患者的 CT 扫描显示，与安慰剂相比，在 9 周（47.8 ± 24.1 与 22.2 ± 12.3mg/cm；p = 0.008）和 14 周（89.7 ± 29.1 与 53.6 ± 21.9mg/cm；p = 0.006）时，骨愈合更快。6 周和 24 周的影像学分析以及 12 个月和 24 个月的随访显示，rhBMP6/ABC 治疗的患者的骨形成和重塑更为先进。总之，我们表明，与单独使用安慰剂相比，rhBMP6/ABC 在 100μg/mL 的剂量下可加速 HTO 患者的骨愈合，且无严重不良事件，具有良好的耐受性。总的来说，这是首次使用客观的骨矿物质密度测量系统，对小梁骨表面的基于 BMP 的成骨植入物与安慰剂的骨愈合效果进行了比较。
