Study Title:

Avandia and Actos are Causing Bone Fractures

Study Abstract

Background: Thiazolidinedione (TZD) treatment has been associated with fractures. The purpose of this study was to examine the association between TZD treatment and fractures in type 2 diabetic patients.

Methods: Using data from Translating Research into Action for Diabetes, a multicenter prospective observational study of diabetes care in managed care, we conducted a matched case-control study to assess the odds of TZD exposure in patients with type 2 diabetes with and without fractures. We identified 786 cases based on fractures detected in health plan administrative data. Up to four controls without any fracture diagnoses were matched to each case. Controls were matched on health plan, date of birth within 5 yr, sex, race/ethnicity, and body mass index within 5 kg/m2. We performed conditional logistic regression for premenopausal and postmenopausal women and men to assess the odds of exposure to potential risk factors for fracture, including medications, self-reported limited mobility, and lower-extremity amputations.

Results: We found statistically significant increased odds of exposure to TZDs, glucocorticoids, loop diuretics, and self-reported limited mobility for women 50 yr of age and older with fractures. Exposure to both loop diuretics and TZDs, glucocorticoids, and insulin and limited mobility and lower-extremity amputation were associated with fractures in men.

Conclusion: Postmenopausal women taking TZDs and the subset of men taking both loop diuretics and TZDs were at increased risk for fractures. In postmenopausal women, risk was associated with higher TZD dose. No difference between rosiglitazone and pioglitazone was apparent.

From press release:

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.

Study Information

Dori Bilik, Laura N. McEwen, Morton B. Brown, Nathan E. Pomeroy, Catherine Kim, Keiko Asao, Jesse C. Crosson, O. Kenrik Duru, Assiamira Ferrara, Victoria C. Hsiao, Andrew J. Karter, Pearl G. Lee, David G. Marrero, Joe V. Selby, Usha Subramanian, W. Herman.
Thiazolidinediones and Fractures: Evidence from Translating Research into Action for Diabetes
J. Clin. Endocrinol. Metab.
2010 July
Departments of Internal Medicine, Biostatistics, and Epidemiology, University of Michigan, Ann Arbor, Michigan 48109.

Full Study