Several professional organizations have recommended tramadol as one of the first-line or second-line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000-2017), five sequential propensity score-matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti-inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase-2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity-score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1-year follow-up, 518 hip fracture (3.7/1000 person-years) occurred in the tramadol cohort and 401 (2.9/1000 person-years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person-years for tramadol, 1.7/1000 person-years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person-years for tramadol, 2.0/1000 person-years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person-years for tramadol, 1.8/1000 person-years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person-years for tramadol, 1.5/1000 person-years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research.

中文翻译：

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使用曲马多与髋部骨折风险的关联。

多个专业组织推荐曲马多作为慢性非癌性疼痛患者的一线或二线疗法之一，其处方在全球范围内迅速增加；然而，曲马多的安全性（例如骨折风险）仍不清楚。本研究旨在探讨曲马多与髋部骨折风险的关系。在英国全科医生健康改善网络 (THIN) 数据库（2000-2017 年）中，在没有髋部骨折、癌症或阿片类药物使用障碍病史的 50 岁或以上的个体中，进行了五项序贯倾向评分匹配队列研究聚集，即开始使用曲马多或开始使用以下药物之一的参与者：可待因（n = 146,956）（另一种常用的弱阿片类药物）、萘普生（n = 115,109）或布洛芬（n = 107,438）（常用的非选择性非甾体类药物）抗炎药 [NSAID]）、塞来考昔 (n = 43,130) 或依托考昔 (n = 27,689)（环氧合酶 2 抑制剂）。结果是一年多的时间里发生髋部骨折。经过倾向得分匹配后，纳入的参与者平均年龄为 65.7 岁，其中 56.9% 为女性。在 1 年随访期间，曲马多组发生 518 例髋部骨折（3.7/1000 人年），可待因组发生 401 例（2.9/1000 人年）。与可待因相比，曲马多导致髋部骨折的风险比 (HR) 为 1.28（95% 置信区间 [CI] 1.13 至 1.46）。曲马多队列的髋部骨折风险也高于萘普生（曲马多为 2.9/1000 人年，萘普生为 1.7/1000 人年；HR = 1.69，95% CI 1.41 至 2.03）、布洛芬（3.4/曲马多为 1000 人年，布洛芬为 2.0/1000 人年；HR = 1.65，95% CI 1.39 至 1.96），塞来昔布（曲马多为 3.4/1000 人年，塞来昔布为 1.8/1000 人年；HR = 1.85，95% CI 1.40 至 2.44）或依托考昔（曲马多为 2.9/1000 人年，依托考昔为 1.5/1000 人年；HR = 1.96，95% CI 1.34 至 2.87）队列。在这项基于人群的队列研究中，与开始使用可待因和常用的非甾体抗炎药相比，开始使用曲马多与髋部骨折的风险较高相关，这表明需要重新审视临床实践中曲马多使用的一些指南。© 2020 美国骨与矿物质研究学会。