Guzman Javier Z, Merrill Robert K, Kim Jun S, Overley Samuel C, Dowdell James E, Somani Sulaiman, Hecht Andrew C, Cho Samuel K, Qureshi Sheeraz A
Department of Orthopedic Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th St, 4th Floor, New York, NY 10029, USA.
Department of Orthopedic Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th St, 4th Floor, New York, NY 10029, USA.
Spine J. 2017 Sep;17(9):1247-1254. doi: 10.1016/j.spinee.2017.04.030. Epub 2017 Apr 26.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely adopted as a fusion adjunct in spine surgery since its approval in 2002. A number of concerns regarding adverse effects and potentially devastating complications of rhBMP-2 use led to a Food and Drug Administration (FDA) advisory issued in 2008 cautioning its use, and a separate warning about its potential complications was published by The Spine Journal in 2011.
To compare trends of rhBMP-2 use in spine surgery after the FDA advisory in 2008 and The Spine Journal warning in 2011.
Retrospective cross-sectional study using a national database.
All patients from 2002 to 2013 who underwent spinal fusion surgery at an institution participating in the Nationwide Inpatient Sample (NIS).
Proportion of spinal fusion surgeries using rhBMP-2.
We queried the NIS from 2002 to 2013 and used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes to identify spinal fusion procedures and those that used rhBMP-2. Procedures were subdivided into primary and revision fusions, and by region of the spine. Cervical and lumbosacral fusions were further stratified into anterior and posterior approaches. The percentage of cases using BMP was plotted across time. A linear regression was fit to the data from quarter 3 of 2008 (FDA advisory) through quarter 1 of 2011, and a separate regression was fit to the data from quarter 2 of 2011 (The Spine Journal warning) onward. The slopes of these regression lines were statistically compared to determine differences in trends. No funding was received to conduct this study, and no authors had any relevant conflicts of interest.
A total of 4,167,079 patients in the NIS underwent spinal fusion between 2002 and 2013. We found a greater decrease in rhBMP-2 use after The Spine Journal warning compared with the FDA advisory for all fusion procedures (p=.006), primary fusions (p=.006), and revision fusions (p=.004). Lumbosacral procedures also experienced a larger decline in rhBMP-2 use after The Spine Journal article as compared with the FDA warning (p=.0008). This pattern was observed for both anterior and posterior lumbosacral fusions (p≤.0001 for both). Anterior cervical fusion was the only procedure that demonstrated a decline in rhBMP-2 use after the FDA advisory that was statistically greater than after The Spine Journal article (p=.02).
Warnings sanctioned through the spine literature may have a greater influence on practice of the spine surgery community as compared with advisories issued by the FDA.Comprehensive guidelines regarding safe and effective use of rhBMP-2 must be established.
自2002年获得批准以来，重组人骨形态发生蛋白-2（rhBMP-2）已被广泛用作脊柱手术中的融合辅助剂。对rhBMP-2使用的不良反应和潜在严重并发症的诸多担忧，促使美国食品药品监督管理局（FDA）在2008年发布了一份咨询意见，对其使用予以警示，并且《脊柱杂志》在2011年发表了关于其潜在并发症的单独警告。
比较2008年FDA咨询意见和2011年《脊柱杂志》警告发布后，rhBMP-2在脊柱手术中的使用趋势。
使用国家数据库的回顾性横断面研究。
2002年至2013年期间，在参与全国住院患者样本（NIS）的机构接受脊柱融合手术的所有患者。
使用rhBMP-2的脊柱融合手术比例。
我们查询了2002年至2013年的NIS，并使用国际疾病分类第九版临床修订本（ICD-9-CM）程序代码来识别脊柱融合手术以及使用rhBMP-2的手术。手术被细分为初次融合和翻修融合，并按脊柱区域划分。使用BMP的病例百分比随时间绘制。对2008年第3季度（FDA咨询意见）至2011年第1季度的数据进行线性回归拟合，对2011年第2季度（《脊柱杂志》警告）之后的数据进行单独回归拟合。对这些回归线的斜率进行统计学比较，以确定趋势差异。未获得开展本研究的资金，且作者均无任何相关利益冲突。
2002年至2013年期间，NIS中共有4167079例患者接受了脊柱融合手术。我们发现，与FDA咨询意见相比，《脊柱杂志》警告发布后，rhBMP-2在所有融合手术（p = 0.006）、初次融合（p = 0.006）和翻修融合（p = 0.004）中的使用下降幅度更大。与FDA警告相比，《脊柱杂志》文章发表后，腰骶部手术中rhBMP-2的使用下降幅度也更大（p = 0.0008）。腰骶部前路和后路融合手术均观察到这种模式（两者p≤0.0001）。颈椎前路融合是唯一一种在FDA咨询意见发布后rhBMP-2使用下降幅度在统计学上大于《脊柱杂志》文章发布后的手术（p = 0.02）。
与FDA发布的咨询意见相比，通过脊柱文献发布的警告可能对脊柱外科界的实践有更大影响。必须制定关于rhBMP-2安全有效使用的综合指南。
