Utrecht Institute for Pharmaceutical Sciences, Utrecht University Utrecht, Netherlands.
Front Endocrinol (Lausanne). 2013 Feb 26;4:11. doi: 10.3389/fendo.2013.00011. eCollection 2013.
The use of thiazolidinediones (TZDs) has been associated with increased fracture risks. Our aim was to estimate the risk of fracture with TZDs in three different healthcare registries, using exactly the same study design, and to perform an individual patient data meta-analysis of these three studies.
Population-based cohort studies were performed utilizing the British General Practice Research Database (GPRD), the Dutch PHARMO Record Linkage System (RLS), and the Danish National Health Registers. In all three databases, the exposed cohort consisted of all patients (aged 18+) with at least one prescription of antidiabetic (AD) medication. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture. The total period of follow-up for each patient was divided into periods of current exposure and past exposure, with patients moving between current and past use.
In all three registries, the risk of fracture was increased for women who were exposed to TZDs: HR 1.48 (1.37-1.60) in GPRD, HR 1.35 (1.15-1.58) in PHARMO, and HR 1.22 (1.03-1.44) in Denmark. Combining the data in an individual patient data meta-analysis resulted, for women, in a 1.4-fold increased risk of any fracture for current TZD users versus other AD drug users [adj. HR 1.44 (1.35-1.53)]. For men, there was no increased fracture risk [adj. HR 1.05 (0.96-1.14)]. Risks were increased for fractures of the radius/ulna, humerus, tibia/fibula, ankle, and foot, but not for hip/femur or vertebral fractures. Current TZD users with more than 25 TZD prescriptions ever before had a 1.6-fold increased risk of fracture compared with other AD drug users [HR 1.59 (1.46-1.74)].
In this study, we consistently found a 1.2- to 1.5-fold increased risk of fractures for women using TZDs, but not for men, across three different healthcare registries. TZD users had an increased risk for fractures of the extremities, and risks further increased for prolonged users of TZDs.
噻唑烷二酮类药物（TZDs）的使用与骨折风险增加有关。我们的目的是在三个不同的医疗保健注册中心使用完全相同的研究设计来估计 TZD 相关的骨折风险，并对这三项研究进行个体患者数据荟萃分析。
使用英国全科医生研究数据库（GPRD）、荷兰 PHARMO 记录链接系统（RLS）和丹麦国家健康登记处进行基于人群的队列研究。在所有三个数据库中，暴露队列均由至少有一次抗糖尿病药物（AD）处方的所有患者（年龄≥18 岁）组成。使用 Cox 比例风险模型来估计骨折的风险比（HR）。每个患者的总随访期分为当前暴露期和既往暴露期，患者在当前使用和既往使用之间移动。
在所有三个注册中心，女性使用 TZD 时骨折风险增加：GPRD 中 HR 为 1.48（1.37-1.60），PHARMO 中 HR 为 1.35（1.15-1.58），丹麦 HR 为 1.22（1.03-1.44）。对个体患者数据进行荟萃分析，结果显示，与其他 AD 药物使用者相比，当前 TZD 使用者的任何骨折风险增加了 1.4 倍[调整 HR 1.44（1.35-1.53）]。对于男性，骨折风险没有增加[调整 HR 1.05（0.96-1.14）]。桡骨/尺骨、肱骨、胫骨/腓骨、踝部和足部骨折风险增加，但髋部/股骨或脊柱骨折风险没有增加。与其他 AD 药物使用者相比，曾经使用过 25 次以上 TZD 处方的当前 TZD 使用者骨折风险增加了 1.6 倍[HR 1.59（1.46-1.74）]。
在这项研究中，我们在三个不同的医疗保健注册中心一致发现，女性使用 TZD 的骨折风险增加了 1.2-1.5 倍，但男性没有增加。TZD 使用者四肢骨折风险增加，长期使用 TZD 的风险进一步增加。
