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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-γ-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 …