Major Finding: Both rosiglitazone and pioglitazone are associated with a 71% increase in the risk of fracture in diabetic women 50 years of age and older. In men with diabetes, there is a 3.5-fold increase in the risk of fracture when TZDs are used together with loop diuretics, but not when TZDs are used alone.
Data Source: Case-control study involving 786 cases of fractures and 2,657 matched controls in patients with type 2 diabetes.
Disclosures: The Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases funded the study. The authors did not report other conflicts of interest.
Rosiglitazone and pioglitazone are both associated with an increased risk of fracture in postmenopausal women with type 2 diabetes, according to a matched case-control study that used data from the Translating Research into Action for Diabetes (TRIAD) trial.
After controlling for age, sex, race/ethnicity, body mass index, and health plan, Dori Bilik of the University of Michigan, Ann Arbor, and colleagues, found that both of the thiazolidinediones (TZDs) were associated with a 71% increase in the risk of fracture for women aged 50 and older, according to the study, published July 14 online.
The investigators detected no such increase in risk for younger women. In men, TZDs alone showed no association with an increase in fracture risk. But men who took both TZDs and loop diuretics experienced a 3.5-fold increase in the risk of fractures.
TRIAD enrolled 11,927 patients with diabetes in 2000–2001. All were at least age 18 years and in managed care for at least 18 months before the baseline patient survey. The investigators analyzed data from patients with type 2 diabetes, excluding those who were diagnosed before age 30 and treated only with insulin. Among these patients were 786 with a diagnosis of fracture, which the investigators matched with 2,657 controls, up to 4 controls per case and followed for a mean of 1.9 years.
“Our study shows that increased fracture risk is associated with higher TZD dose, but no difference between rosiglitazone and pioglitazone is apparent, suggesting a class effect of TZDs on fracture risk,” said senior author Dr. William Herman of the University of Michigan Ann Arbor, in a prepared statement. “Physicians should be aware of this risk and weigh the benefits and risks of therapy when they initially prescribe or renew prescriptions for TZDs.”
Researchers found a dose-response relationship between TZDs and fracture risk. Higher TZD doses were associated with a significant 42% increase in the odds of fractures for women aged 50 years and older, but not for women under 50 years or for men (J. Clin. Endocrinol. Metab. 2010 July 14 [doi:10.1210/jc2009-2638]).