Context: Thiazolidenediones (TZDs) are selective ligands of PPAR gamma and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral anti-diabetic agents.

Objective: To determine the association between TZD use and fracture risk among older adults with diabetes.

Design: A cohort study.

Participants: Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent.

Main Outcome: Fracture.

Results: Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. While not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk [RR] 1.31, 95% confidence interval [CI] 0.98 – 1.77, p = 0.071) or a sulfonylurea (RR 1.21, 95% CI 0.94 – 1.55, p = 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylureas was 200 and was 111 comparing TZDs with metformin.

Conclusions: As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin.