Mellanby Centre for Musculoskeletal Research, Medical Research Council (MRC) Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK.
Department of Trauma and Spine Surgery, The Second People's Hospital of Wuhu, Wuhu, China.
J Bone Miner Res. 2022 Jun;37(6):1117-1124. doi: 10.1002/jbmr.4548. Epub 2022 Apr 20.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. We explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well-documented, randomized, placebo-controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p < 0.001) than nonusers, with slightly higher femoral neck bone mineral density (FN-BMD, 0.66 versus 0.64 g/cm , p < 0.001). In an adjusted model, NSAID use was associated with a significant increase in osteoporotic fracture risk over the 3-year study period (hazard ratio [HR] 1.27; 95% confidence interval [CI], 1.01-1.62; p = 0.039). However, this increase in risk was not statistically significant in the placebo group (HR 1.11; 95% CI, 0.81-1.52). In women receiving clodronate, the effect of the bisphosphonate to reduce osteoporotic fracture risk was not observed in those receiving NSAIDs (HR 0.95; 95% CI, 0.65-1.41; p = 0.81) in contrast to those not using NSAIDs (HR 0.71; 95% CI, 0.58-0.89; p = 0.002). In a subset with hip BMD repeated at 3 years, BMD loss during clodronate therapy was greater in those women receiving NSAIDs than in nonusers (eg, total hip -2.75% versus -1.27%, p = 0.078; femoral neck -3.06% versus -1.12%, p = 0.028), and was not significantly different from that observed in women receiving placebo. The efficacy of the bisphosphonate, clodronate, to reduce fracture risk was largely negated in those receiving NSAIDs. Although the mechanism is unclear, this clinically significant observation requires exploration in studies of commonly used bisphosphonates. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
非甾体抗炎药 (NSAIDs) 已被报道对骨骼健康具有微弱但有益的影响，包括骨折风险，但许多流行病学研究可能存在混杂因素。我们在一项关于双膦酸盐氯膦酸盐的随机、安慰剂对照研究的事后分析中探讨了 NSAIDs 与骨折风险之间的关系，该研究表明氯膦酸盐治疗可使骨质疏松性骨折风险降低 23%。在基线时使用同时使用的药物来确定开了口服 NSAIDs 的患者。只有经过验证的、新发生的骨折才被纳入分析。共有 1082 名（20.8%）女性报告在基线时使用了 NSAIDs。与未使用者相比，她们的年龄略大（平均年龄 79 岁比 80 岁，p=0.004），体重略高（平均体重 66.7 公斤比 64.7 公斤，p<0.001），股骨颈骨密度（FN-BMD）略高（0.66 克/厘米比 0.64 克/厘米，p<0.001）。在调整后的模型中，与 3 年研究期间相比，NSAID 使用者的骨质疏松性骨折风险显著增加（风险比 [HR] 1.27；95%置信区间 [CI]，1.01-1.62；p=0.039）。然而，在安慰剂组中，这种风险增加并不具有统计学意义（HR 1.11；95%CI，0.81-1.52）。在接受氯膦酸盐治疗的女性中，接受 NSAIDs 的女性与未接受 NSAIDs 的女性（HR 0.95；95%CI，0.65-1.41；p=0.81）相比，双膦酸盐降低骨质疏松性骨折风险的效果并不明显，而未接受 NSAIDs 的女性（HR 0.71；95%CI，0.58-0.89；p=0.002）。在一组髋关节 BMD 在 3 年内重复的患者中，与未使用者相比，接受 NSAIDs 的女性在氯膦酸盐治疗期间的 BMD 丢失更大（例如，全髋关节 -2.75%比 -1.27%，p=0.078；股骨颈 -3.06%比 -1.12%，p=0.028），与接受安慰剂的女性相比没有显著差异。双膦酸盐氯膦酸盐降低骨折风险的疗效在接受 NSAIDs 的女性中基本被否定。虽然机制尚不清楚，但这一具有临床意义的观察结果需要在常用双膦酸盐的研究中进行探讨。
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