Division of Rheumatology (M.D.G. and J.F.B.), Department of Biostatistics, Epidemiology, and Informatics (M.D.G., J.F.B., C.E.L., T.A.M., and S.H.), and the Department of Orthopedic Surgery (S.M.), University of Pennsylvania, Philadelphia, Pennsylvania.
J Bone Joint Surg Am. 2020 Jul 15;102(14):1230-1238. doi: 10.2106/JBJS.19.01415.
Cyclooxygenase-2 (COX-2) has been found to be important for fracture-healing in animal models, raising concerns about use of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors after fractures. We evaluated associations of NSAIDs, COX-2 inhibitors, and opioids with nonunion after long-bone fracture.
Using private health insurance claims data from Optum's de-identified Clinformatics Data Mart database from January 1, 2000, to September 30, 2015, we identified adults with a single long-bone fracture or commonly paired long-bone fractures who had 1 year of available follow-up data. Using multivariable logistic regression models, we examined associations between NSAID, COX-2-inhibitor, or opioid prescription fills after the fracture and the risk of nonunion within 1 year, defined as a nonunion diagnosis with a procedure to treat the nonunion.
A nonunion diagnosis with a procedure to treat the nonunion was identified after 2,996 (0.9%) of the 339,864 fracture episodes, with rates varying by fracture site. The risk of that outcome was greater in patients who had filled COX-2-inhibitor prescriptions (adjusted odds ratio = 1.84 [95% confidence interval = 1.38 to 2.46]) or opioid prescriptions (1.69 [1.53 to 1.86]), but not in patients who had filled nonselective-NSAID prescriptions (1.07 [0.93 to 1.23]) after the fracture. Results were similar when the outcome definition was changed to just a nonunion diagnosis.
COX-2 inhibitors, but not nonselective NSAIDs, were associated with a greater risk of nonunion after fracture. Opioids were also associated with nonunion risk, although patients filling prescriptions for opioids may have had more severe fractures.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
环氧化酶-2（COX-2）在动物模型中对于骨折愈合非常重要，这引起了人们对于骨折后使用非甾体抗炎药（NSAIDs）和选择性 COX-2 抑制剂的担忧。我们评估了 NSAIDs、COX-2 抑制剂和阿片类药物与长骨骨折后骨不连的关系。
使用 Optum 的匿名 Clinformatics Data Mart 数据库中的私人健康保险索赔数据，我们从 2000 年 1 月 1 日至 2015 年 9 月 30 日，确定了有单一长骨骨折或常见配对长骨骨折且有 1 年可随访数据的成年人。使用多变量逻辑回归模型，我们检查了骨折后 NSAID、COX-2 抑制剂或阿片类药物处方与 1 年内非愈合风险之间的关系，非愈合定义为非愈合诊断和治疗非愈合的手术。
在 339864 例骨折事件中，有 2996 例（0.9%）出现了非愈合诊断和治疗非愈合的手术，骨折部位不同，发生率也不同。与未服用 NSAID 的患者相比，服用 COX-2 抑制剂（调整后的优势比=1.84 [95%置信区间=1.38 至 2.46]）或阿片类药物（1.69 [1.53 至 1.86]）的患者发生该结果的风险更高，但未服用非选择性 NSAID 的患者（1.07 [0.93 至 1.23]）的风险则没有增加。当将结局定义改为仅为非愈合诊断时，结果相似。
COX-2 抑制剂而非非选择性 NSAIDs 与骨折后骨不连风险增加相关。阿片类药物也与非愈合风险相关，尽管服用阿片类药物处方的患者可能有更严重的骨折。
治疗性 III 级。有关证据水平的完整说明，请参阅作者说明。
