Postmenopausal women with diabetes taking TZDs at increased fracture risk

Postmenopausal women with diabetes taking thiazolidinediones (TZDS), including rosiglitazone and pioglitazone, may be at increased risk for fractures according to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM). Men with diabetes taking both loop diuretics and TZDs may also be at increased risk of fractures.

"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 William Herman, MD, MPH, of the University of Michigan in Ann Arbor and senior author of the study. "Physicians should be aware of this risk and weigh the benefits and risks of therapy when they initially prescribe or renew prescriptions for TZDs."

Using data from Translating Research into Action for Diabetes (TRIAD), a multi-center prospective observational study of diabetes care in managed care, researchers conducted a matched case-control study to assess the odds of TZD exposure in patients with type 2 diabetes with and without fractures. From the study, researchers identified 786 cases of fractures and 2,657 matched controls (diabetes patients without fractures).

Women aged 50 years and older with fractures, when compared to their matched controls, were significantly more likely to have filled prescriptions for TZDs. Men with fractures were more likely to have filled prescriptions for TZDs and loop diuretics when compared to their matched controls. This result is particularly interesting because in men, loop diuretics or TZDs alone did not confer significant risks.

"Future studies, particularly long-term, prospective randomized clinical trials will be needed to conclusively demonstrate small to moderate harm," said Herman.

Other researchers working on the study include: Doris Bilik, Laura McEwen, Morton Brown, Catherine Kim, Keiko Asao, Victoria Hsiao and Pearl Lee of the University of Michigan in Ann Arbor; Nathan Pomeroy of the Center for Diabetes and Endocrinology in Grand Rapids, Mich.; Jesse Crosson of UMDNJ-Robert Wood Johnson Medical School in Somerset, N.J.; O. Kenrik Duru of the University of California in Los Angeles; Assiamira Ferrara, Andrew Karter and Joe Selby of Kaiser Permanente in Oakland, Calif.; and David Marrero and Usha Subramanian of Indiana University School of Medicine in Indianapolis.

The article, "Thiazolidinediones and Fractures: Evidence from Translating Research into Action for Diabetes (TRIAD)," will appear in the October 2010 issue of JCEM.