Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA 02120, USA.
J Bone Miner Res. 2012 Apr;27(4):789-96. doi: 10.1002/jbmr.1489.
Several prior investigations demonstrate an improvement in bone mineral density associated with use of tumor necrosis factor inhibitors (TNFi). We compared the risk of osteoporotic fractures among patients with rheumatoid arthritis (RA) initiating a disease-modifying antirheumatic drug (DMARD). A population-based cohort study was conducted using health care utilization data (1996-2008) from a Canadian province and a U.S. commercial insurance plan. Patients with at least two RA diagnoses were identified, and follow-up began with the first prescription for a DMARD. Drug regimens were categorized into three mutually exclusive hierarchical groups: (1) TNFi with or without nonbiologic DMARDs (nbDMARD), (2) methotrexate (MTX) without a TNFi, or (3) other nbDMARD without a TNFi or MTX. Main outcomes were hospitalizations for fractures of the hip, wrist, humerus, or pelvis based on diagnoses and procedure codes. The study cohort consisted of 16,412 RA patients with 25,988 new treatment episodes: 5856 TNFi, 12,554 MTX, and 7578 other nbDMARD. The incidence rate per 1000 person-years for osteoporotic fracture were 5.11 [95% confidence interval (CI) 3.50-7.45] for TNFi, 5.35 (95% CI 4.08-7.02) for MTX, and 6.38 (95% CI 3.78-10.77) for other nbDMARD. After multivariable adjustment for osteoporosis and fracture-related risk factors, the risk of nonvertebral osteoporotic fracture was not different in either TNFi [hazard ratio (HR) 1.07, 95% CI 0.57-1.98] or MTX (HR 1.18, 95% CI 0.60-2.34) compared with nbDMARD. Among subjects diagnosed with RA, the adjusted risk of nonvertebral fracture was similar across persons starting a TNFi, MTX, or other nbDMARD.
先前有几项研究表明，使用肿瘤坏死因子抑制剂（TNFi）可提高骨密度。我们比较了起始使用疾病修饰抗风湿药物（DMARD）的类风湿关节炎（RA）患者的骨质疏松性骨折风险。本研究采用加拿大省级医疗保健利用数据（1996-2008 年）和美国商业保险计划进行了一项基于人群的队列研究。至少确诊两次 RA 的患者被确定为研究对象，随访从首次处方 DMARD 开始。药物方案分为三个互斥的分层组：（1）TNFi 联合或不联合非生物性 DMARD（nbDMARD），（2）甲氨蝶呤（MTX）不联合 TNFi，或（3）其他 nbDMARD 不联合 TNFi 或 MTX。主要结局是基于诊断和手术代码的髋部、腕部、肱骨或骨盆骨折住院。研究队列包含 16412 名 RA 患者，共 25988 例新治疗发作：5856 例 TNFi、12554 例 MTX 和 7578 例其他 nbDMARD。骨质疏松性骨折的发生率为每 1000 人年 5.11（95%置信区间[CI]3.50-7.45），TNFi 组为 5.35（95%CI 4.08-7.02），MTX 组为 6.38（95%CI 3.78-10.77），其他 nbDMARD 组为 6.38（95%CI 3.78-10.77）。对骨质疏松症和骨折相关危险因素进行多变量调整后，TNFi [风险比（HR）1.07，95%置信区间（CI）0.57-1.98]或 MTX（HR 1.18，95%CI 0.60-2.34）与 nbDMARD 相比，非椎体骨质疏松性骨折风险无差异。在确诊为 RA 的患者中，起始使用 TNFi、MTX 或其他 nbDMARD 的患者，非椎体骨折的调整风险相似。
