Risk of Fracture with Thiazolidinediones: Disease or Drugs?
Risk of Fracture with Thiazolidinediones: Disease or Drugs?
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DOI：
10.1007/s00223-012-9591-8
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发表时间：
2012-06-01
影响因子：
4.2
通讯作者：
de Vries, Frank
中科院分区：
文献类型：
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作者：
Bazelier, Marloes T.;Vestergaard, Peter;de Vries, Frank
使用噻唑烷二酮类药物(TZD)会增加骨折风险。此外，2型糖尿病(T2 DM)与骨折有关。我们评估了TZD的使用和骨折风险之间的关联与药物或潜在疾病之间的关联程度。我们使用丹麦国家健康登记处(1996-2007)进行了一项基于人群的队列研究，该登记处将药房数据与国家医院登记处联系起来。口服降糖药使用者(=180,049)与非口服降糖药使用者按出生年份和性别1：3匹配。用COX比例风险模型估计骨折的危险比(HR)。对年龄、合并症和药物使用进行了时间相关的调整。我们创建了一个疾病严重程度的替代指标。第一阶段被定义为当前使用双胍或磺胺，第二阶段为当前同时使用双胍和磺胺，第三阶段为使用TZDS的患者，第四阶段为使用胰岛素的患者。与对照组相比，第3期和第4期骨质疏松性骨折的风险增加了1.3倍。目前使用TZD的风险(3期HR=1.27，95%可信区间1.06-1.52)和当前使用胰岛素的风险(4期HR=1.25，95%CI 1.20-1.31)相似。第1期(HR=1.15，95，CI为1.13~1.18)和第2期(HR=1.00，95，CI为0.96~1.04)的危险性较低。服用TZD和服用胰岛素的患者发生骨质疏松性骨折的风险相似。在研究TZD的骨折风险时，应考虑潜在的T2 DM。
The use of thiazolidinediones (TZDs) has been associated with an increased fracture risk. In addition, type 2 diabetes mellitus (T2DM) has been linked with fracture. We evaluated to what extent the association between TZD use and fracture risk is related to the drug or to the underlying disease. We conducted a population-based cohort study using the Danish National Health Registers (1996-2007), which link pharmacy data to the national hospital registry. Oral antidiabetic users ( = 180,049) were matched 1:3 by year of birth and sex to nonusers. Cox proportional hazards models were used to estimate hazard ratios (HRs) of fracture. Time-dependent adjustments were made for age, comorbidity, and drug use. We created a proxy indicator for the severity of disease. The first stage was defined as current use of either a biguanide or a sulfonyluerum, the second stage as current use of a biguanide and a sulfonyluerum at the same time, the third stage as patients using TZDs, and the fourth stage as patients using insulin. The risk of osteoporotic fracture was increased 1.3-fold for stages 3 and 4 compared with controls. Risk with current TZD use (stage 3 HR = 1.27, 95 % CI 1.06-1.52) and risk with current use of insulin (stage 4 HR = 1.25, 95 % CI 1.20-1.31) were similar. In the first (HR = 1.15, 95 similar to CI 1.13-1.18) and second (HR = 1.00, 95 similar to CI 0.96-1.04) stages risks were lower. Risk of osteoporotic fracture was similar for TZD users and insulin users. When studying fracture risk with TZDs, the underlying T2DM should be taken into account.