Centre for Reviews and Dissemination, University of York, York, United Kingdom.
Ann Intern Med. 2013 Jun 18;158(12):877-89. doi: 10.7326/0003-4819-158-12-201306180-00005.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used to promote fusion in spinal surgery, but its safety has been questioned.
To evaluate the effectiveness and safety of rhBMP-2.
Individual-participant data obtained from the sponsor or investigators and data extracted from study publications identified by systematic bibliographic searches through June 2012.
Randomized, controlled trials of rhBMP-2 versus iliac crest bone graft (ICBG) in spinal fusion surgery for degenerative disc disease and related conditions and observational studies in similar populations for investigation of adverse events.
Individual-participant data from 11 eligible of 17 provided trials sponsored by Medtronic (Minneapolis, Minnesota) (n = 1302) and 1 of 2 other eligible trials (n = 106) were included. Additional aggregate adverse event data were extracted from 35 published observational studies.
Primary outcomes were pain (assessed with the Oswestry Disability Index [ODI] or Short Form-36), fusion, and adverse events. At 24 months, ODI scores were 3.5% lower (better) with rhBMP-2 than with ICBG (95% CI, 0.5% to 6.5%) and radiographic fusion was 12% higher (CI, 2% to 23%). At or shortly after surgery, pain was more common with rhBMP-2 (odds ratio, 1.78 [CI, 1.06 to 2.95]). Cancer was more common after rhBMP-2 (relative risk, 1.98 [CI, 0.86 to 4.54]), but the small number of events precluded definite conclusions.
The observational studies were diverse and at risk of bias.
At 24 months, rhBMP-2 increases fusion rates, reduces pain by a clinically insignificant amount, and increases early postsurgical pain compared with ICBG. Evidence of increased cancer incidence is inconclusive.
Yale University Open Data Access Project.
重组人骨形态发生蛋白-2（rhBMP-2）广泛用于促进脊柱手术融合，但安全性受到质疑。
评估 rhBMP-2 的有效性和安全性。
从赞助商或研究者处获得的个体参与者数据，以及通过系统文献检索从研究出版物中提取的数据，检索时间截至 2012 年 6 月。
rhBMP-2 与髂嵴骨移植物（ICBG）在退行性椎间盘疾病和相关疾病的脊柱融合手术中的随机对照试验，以及在类似人群中调查不良事件的观察性研究。
从由美敦力（明尼苏达州明尼阿波利斯市）赞助的 17 项合格试验中的 11 项（n=1302）和另外 2 项合格试验中的 1 项（n=106）中提取个体参与者数据。还从 35 项已发表的观察性研究中提取了汇总不良事件数据。
主要结局是疼痛（用 Oswestry 残疾指数[ODI]或简明 36 项健康调查[SF-36]评估）、融合和不良事件。在 24 个月时，rhBMP-2 的 ODI 评分比 ICBG 低 3.5%（更好）（95%CI，0.5%至 6.5%），影像学融合率高 12%（CI，2%至 23%）。在手术时或之后不久，rhBMP-2 更常见疼痛（比值比，1.78[CI，1.06 至 2.95]）。rhBMP-2 后癌症更常见（相对风险，1.98[CI，0.86 至 4.54]），但事件数量较少，无法得出明确结论。
观察性研究差异较大且存在偏倚风险。
在 24 个月时，rhBMP-2 与 ICBG 相比，增加融合率，减轻疼痛（临床意义不大），并增加术后早期疼痛。癌症发病率增加的证据尚无定论。
耶鲁大学开放数据获取项目。
