William Herman, MD, MPH
TZD drugs such as Avandia and Actos are associated with bone fractures in type 2 diabetes patients
ANN ARBOR, July 14, 2010 — Postmenopausal women with diabetes taking thiazolidinediones (TZDs), including rosiglitazone and pioglitazone (including the popular diabetes drugs Avandia and Actos), may be at increased risk for bone fractures, according to a new study announced in an advance online publication of the manuscript in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).
Additionally, men with diabetes taking both loop diuretics (such as such as Lasix or Bumex) 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 the Translating Research into Action for Diabetes (TRIAD) study, 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 matched controls (diabetes patients without fractures).
Women aged 50 years and older with fractures, when compared to diabetes patients without fractures, 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 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," said Herman. Dr. Herman is Stefan S. Fajans/GlaxoSmithKline Professor of Diabetes, Professor of Internal Medicine and Epidemiology, and Director of the Michigan Diabetes Research and Training Center.
When asked whether there are safer medications than Actos and Avandia for diabetes treatment in the at-risk group, Herman stated, "There are several different classes of medications available for the management of type 2 diabetes, and each class has advantages and disadvantages. 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 post-menopausal 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 said. "Whether bisphosphonate medications, such as Fosamax, can reduce the risk of fractures in this setting is unknown."
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, Michigan; 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.
The article, "Thiazolidinediones and Fractures: Evidence from Translating Research into Action for Diabetes (TRIAD) ," will appear in the October 2010 issue of Journal of Clinical Endocrinology & Metabolism.