Medical Research Institute, University of Dundee, Ninewells Hospital & Medical School, Dundee, Scotland DD1 9SY, UK.
Diabetologia. 2012 Nov;55(11):2929-37. doi: 10.1007/s00125-012-2668-0. Epub 2012 Sep 4.
AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes.
Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008.
There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p = 3 × 10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%).
CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.
目的/假设：噻唑烷二酮（TZDs）的现行药物标签警告称会增加骨折风险，主要是女性的远端骨折。我们研究了 TZDs 暴露是否会影响女性和男性的髋部骨折，并将风险与其他用于糖尿病的药物进行了比较。
我们使用苏格兰 2 型糖尿病患者的全国性处方、住院和死亡数据库，计算了 206672 名个体的 TZD 暴露情况。离散时间失效分析用于对 1999-2008 年期间累积药物暴露对髋部骨折的影响进行建模。
在 37479 名暴露个体中有 176 例髋部骨折。随着 TZD 累积暴露量的增加，髋部骨折风险增加：每年暴露的 OR 为 1.18（95%CI 1.09，1.28；p=3×10(-5)），校正年龄、性别和日历月后。在男性（OR 1.20；95%CI 1.03，1.41）和女性（OR 1.18；95%CI 1.07，1.29）中，髋部骨折随着累积暴露量的增加而增加，吡格列酮（OR 1.18）和罗格列酮（OR 1.16）的风险相似。在调整了其他糖尿病药物和其他潜在混杂因素的暴露后，这种关联也是相似的。在本分析中，与磺酰脲类、二甲双胍或胰岛素的累积暴露没有与髋部骨折相关。无论是否使用 TZD，髋部骨折 90 天死亡率相似（曾使用者 15%，未使用者 13%）。
结论/解释：髋部骨折是 TZDs 的严重不良事件，影响两性；标签应更改以警告这一点。超额死亡率至少与报告的吡格列酮与膀胱癌的关联一样多。
