Department of Orthopaedic Surgery, University of Rochester, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA.
J Bone Joint Surg Am. 2013 Sep 4;95(17):1546-53. doi: 10.2106/JBJS.L.01730.
Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has increased considerably since its introduction in 2002. The complications associated with high-dose rhBMP-2 (≥ 40 mg) are unknown. The purpose of our study was to determine outcomes and medical and surgical complications associated with high-dose rhBMP-2 at short-term and long-term follow-up evaluations.
Five hundred and two consecutive adult patients who had received high-dose rhBMP-2 as a part of spinal surgery from 2002 to 2009 at one institution were enrolled. Data were entered prospectively and studied and analyzed retrospectively. Surgical procedures in the thoracic and lumbar spine were included. Major and minor complications were documented intraoperatively, perioperatively, and at the latest follow-up examination. Complications potentially associated with rhBMP-2 use were evaluated for correlation with rhBMP-2 dose. Scoliosis Research Society (SRS) and Oswestry Disability Index (ODI) outcome measures were obtained before and after surgery.
On average, 115 mg (range, 40 to 351 mg) of rhBMP-2 was used. The average age of the patients (410 women and ninety-two men) at the time of the index procedure was 52.4 years (range, eighteen to eighty years). There were 265 primary and 237 revision procedures, and 261 patients had interbody fusion. An average of 11.5 vertebrae were instrumented. The average duration of follow-up was forty-two months (range, fourteen to ninety-two months). The diagnoses included idiopathic scoliosis (41%), degenerative scoliosis (31%), fixed sagittal imbalance (18%), and other diagnoses (10%). The rate of intraoperative complications was 8.2%. The rate of perioperative major surgical complications was 11.6%. The rate of perioperative major medical complications was 11.6%. Minor medical complications occurred in 18.9% of the cases, and minor surgical complications occurred in 2.6%. Logistic regression analysis and Pearson correlation did not identify a significant correlation between rhBMP-2 dosage and radiculopathy (r = -0.006), seroma (r = -0.003), or cancer (r = -0.05). Significant improvements in the ODI score (from a mean of 41 points to a mean of 26 points; p < 0.001) and the SRS total score (from a mean of 3.0 points to a mean of 3.7 points; p < 0.001) were noted at the latest follow-up evaluation.
This is the largest study of which we are aware that examines complications associated with high-dose rhBMP-2. Major surgical complications occurred in 11.6% of patients, and 11.6% experienced major medical complications. There was a cancer prevalence of 3.4%, but no correlation between increasing rhBMP-2 dosage and cancer, radiculopathy (seen in 1% of the patients), or seroma (seen in 0.6%) was found.
自 2002 年重组人骨形态发生蛋白-2（rhBMP-2）问世以来，其使用量大幅增加。目前尚不清楚高剂量 rhBMP-2（≥40mg）相关的并发症。本研究旨在确定高剂量 rhBMP-2 在短期和长期随访评估中与相关的结局和医疗及手术并发症。
在一家机构，2002 年至 2009 年期间，502 例连续接受高剂量 rhBMP-2 作为脊柱手术一部分的成年患者被纳入研究。数据被前瞻性录入，并进行回顾性研究和分析。纳入胸腰椎的手术。记录了术中、围手术期和最新随访检查时的主要和次要并发症。评估了与 rhBMP-2 使用相关的潜在并发症与 rhBMP-2 剂量的相关性。在手术前后采用脊柱研究协会（SRS）和 Oswestry 功能障碍指数（ODI）进行评估。
平均使用 115mg rhBMP-2（范围：40-351mg）。索引手术时患者的平均年龄（410 名女性和 92 名男性）为 52.4 岁（范围：18-80 岁）。有 265 例初次手术和 237 例翻修手术，261 例患者行椎间融合。平均植入 11.5 个节段。平均随访时间为 42 个月（范围：14-92 个月）。诊断包括特发性脊柱侧凸（41%）、退行性脊柱侧凸（31%）、固定矢状面失平衡（18%）和其他诊断（10%）。术中并发症发生率为 8.2%。围手术期主要手术并发症发生率为 11.6%。围手术期主要医疗并发症发生率为 11.6%。发生轻微医疗并发症的比例为 18.9%，轻微手术并发症的比例为 2.6%。Logistic 回归分析和 Pearson 相关性分析均未发现 rhBMP-2 剂量与神经根病（r=-0.006）、血清肿（r=-0.003）或癌症（r=-0.05）之间存在显著相关性。在最新随访时，ODI 评分（从平均 41 分提高至平均 26 分；p<0.001）和 SRS 总分（从平均 3.0 分提高至平均 3.7 分；p<0.001）均显著改善。
这是我们所知的最大规模的研究，旨在评估高剂量 rhBMP-2 相关的并发症。11.6%的患者发生主要手术并发症，11.6%的患者发生主要医疗并发症。癌症患病率为 3.4%，但未发现 rhBMP-2 剂量增加与癌症、神经根病（见于 1%的患者）或血清肿（见于 0.6%的患者）之间存在相关性。
