In both observational studies and randomized trials, thiazolidinediones (TZDs; pioglitazone and rosiglitazone) have been associated with elevated risk for fractures. Biologic plausibility exists: TZDs affect bone metabolism through activation of PPAR-[gamma]-receptors in bone.
This new case-control study was drawn from a prospective observational study of 12,000 patients with type 2 diabetes at multiple U.S. sites. Cases were 786 patients who experienced fractures during a 3-year period; four control patients (matched for sex, age, and body-mass index) were selected for each case patient. In multivariate analysis with adjustment for clinical variables and other medications, TZD use was associated with significantly increased risk for fractures in women aged 50 and older (odds ratio, 1.7). Higher TZD doses were associated with greater fracture risk than lower doses. Risk was increased equally with pioglitazone and rosiglitazone. In men, a 1.4 odds ratio for fractures did not reach statistical significance.
Comment: One important aspect of this study is that outcomes were virtually identical with pioglitazone and rosiglitazone, suggesting that TZD-associated fracture risk is a class effect. Pioglitazone is still on the market; clinicians should consider this potential complication when they choose antidiabetic drugs.
Fuente: Bilik D et al. Thiazolidinediones and fractures: Evidence from Translating Research into Action for Diabetes. J Clin Endocrinol Metab 2010 Oct; 95:4560. [Medline® Abstract]