ANN ARBOR, Mich. — Postmenopausal women taking certain diabetes medications, including the popular drugs Avandia and Actos, may be at increased risk for bone fractures, according to a new study led by the University of Michigan Health System.
The study of more than 3,000 patients showed risk for fractures was higher among patients who took thiasolidinediones, including rosiglitazone and pioglitazone.
Men with diabetes taking both loop diuretics such as such as Lasix or Bumex and TZDs may also be at increased risk of fractures.
The study was published online ahead of print in the Endocrine’s Society’s Journal of Clinical Endocrinology & Metabolism.
“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,” says senior author William Herman, M.D., M.P.H., professor of internal medicine and epidemiology at the U-M and Director of the Michigan Diabetes Research and Training Center.
“Physicians should be aware of this risk and weigh the benefits and risks of therapy when they initially prescribe or renew prescriptions for TZDs,” Herman says.
Using data from the Translating Research into Action for Diabetes study, or TRIAD, a multi-center prospective observational study of diabetes care in managed care, the 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 diabetes patients without fractures.
Women age 50 and older with fractures were significantly more likely to have filled prescriptions for TZDs than those who had not suffered a break.
Men with fractures were more likely to have filled prescriptions for TZDs and loop diuretics when compared to those who did not have fractures. 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,” says Herman who is also the Stefan S. Fajans/GlaxoSmithKline professor of diabetes at U-M.
Herman offers some guidance to those age 50 and older who are looking for safer medications.
“There are several different classes of medications available for the management of type 2 diabetes, and each class has advantages and disadvantages,” he says. “The optimal medication or combination of medications is best determined by a patient’s physician. TZDs such as Avandia or Actos would probably not be the best first-line treatment for postmenopausal women with known osteoporosis or history of fractures.”
If women must take one of the thiazolidinediones, it is unclear whether they can help lower their risk of fractures associated with the medications.
“It is important to consume adequate calcium and vitamin D,” Herman says. “Whether bisphosphonate medications, such as Fosamax, can reduce the risk of fractures in this setting is unknown.”
Additional authors: Doris Bilik, Laura McEwen, Morton Brown, Catherine Kim, Keiko Asao, Victoria Hsiao and Pearl Lee of the University of Michigan; 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, California; and David Marrero and Usha Subramanian of Indiana University School of Medicine in Indianapolis.
Reference: “Thiazolidinediones and Fractures: Evidence from Translating Research into Action for Diabetes (TRIAD)” doi:10.1210/jc.2009-2638
U-M Comprehensive Diabetes Center
Michigan Diabetes Research and Training Center
Adapted from the JCEM press release
Media contact: Shantell Kirkendoll