Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Pharmacoepidemiol Drug Saf. 2012 May;21(5):507-14. doi: 10.1002/pds.3234. Epub 2012 Mar 6.
Clinical and observational studies suggest that use of thiazolidinediones (TZDs) is associated with an increased fracture risk. In addition, type 2 diabetes mellitus (T2DM) is a risk factor for osteoporotic fracture. Our aim was to estimate fracture risks in TZD users and users of other antidiabetic drugs, classified according to proxies of disease severity.
We conducted a population-based cohort study utilizing the Dutch PHARMO database (1998-2008). PHARMO links pharmacy-dispensing data to the National Hospital Registry. Oral antidiabetic users (n = 123,452) were matched 1:4 by year of birth and sex to non-users. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture in TZD users. We created a proxy indicator for disease severity. The first stage was defined as current use of either a biguanide or a sulfonylureum, the second stage as current use of a biguanide and a sulfonylureum at the same time, the third stage was assigned to patients using TZDs and the fourth stage to patients using insulin.
The risk of osteoporotic fracture was increased 1.5-fold (HR 1.49, 95%CI 1.28-1.73) in patients who currently used TZDs (stage 3), and for patients using insulin (stage 4), the risk was increased 1.2-fold (HR 1.24, 1.14-1.36), as compared with controls. In the first and second stages, risks were lower: HR 1.11 (1.06-1.17) for stage 1 and HR 1.03 (0.96-1.11) for stage 2.
When observational studies assess risk of fracture in patients with TZDs, the severity of T2DM should be taken into account.
临床和观察性研究表明，噻唑烷二酮类药物（TZDs）的使用与骨折风险增加有关。此外，2 型糖尿病（T2DM）也是骨质疏松性骨折的一个危险因素。我们的目的是评估 TZD 使用者和其他抗糖尿病药物使用者的骨折风险，这些药物根据疾病严重程度的替代指标进行分类。
我们进行了一项基于人群的队列研究，利用荷兰 PHARMO 数据库（1998-2008 年）。PHARMO 将药房配药数据与国家医院登记处联系起来。口服抗糖尿病药物使用者（n=123452）按出生年份和性别与非使用者 1:4 匹配。使用 Cox 比例风险模型估计 TZD 使用者骨折的风险比（HR）。我们创建了一个疾病严重程度的替代指标。第一阶段定义为当前同时使用二甲双胍或磺脲类药物，第二阶段定义为当前同时使用二甲双胍和磺脲类药物，第三阶段分配给使用 TZDs 的患者，第四阶段分配给使用胰岛素的患者。
与对照组相比，当前使用 TZDs（第 3 阶段）的患者骨质疏松性骨折的风险增加了 1.5 倍（HR 1.49，95%CI 1.28-1.73），而当前使用胰岛素（第 4 阶段）的患者风险增加了 1.2 倍（HR 1.24，1.14-1.36）。在第一和第二阶段，风险较低：第 1 阶段的 HR 为 1.11（1.06-1.17），第 2 阶段的 HR 为 1.03（0.96-1.11）。
当观察性研究评估 TZD 患者骨折风险时，应考虑 T2DM 的严重程度。
