Diabetes Health Center

More Evidence Links Fractures to Diabetes Drugs

July 29, 2010 -- The popular diabetes drugs Actos and Avandia  boost the risk of fracture in older women, according to findings from a new study that echo those of earlier research.

For the new study, researcher William H. Herman, MD, MPH, professor of medicine and epidemiology at the University of Michigan, Ann Arbor, evaluated a large database of managed care patients who had diabetes. He found that those who suffered fractures were more likely to be taking the class of drugs known as TZDs (thiazolidinediones), such as Actos and Avandia.

The fracture risk he found, Herman tells WebMD, was primarily among postmenopausal women, who already tend to have lower bone density. "Diabetic women over 50 with fractures were 70% more likely to be taking a TZD drug than women without fractures," he says.

The study is published online in the Journal of Clinical Endocrinology & Metabolism.

"A lot of the focus [with this class of drugs] has been on cardiovascular risk," Herman tells WebMD. Recently, an FDA advisory panel voted to keep the drug Avandia, linked with a higher risk of death and cardiovascular problems in older patients, on the market, but with stronger warnings.

But Herman notes that the side effect of fractures is also important to examine. "Fractures do have a major impact on quality of life," he says.

Diabetes Drugs and Fracture Risk: A Closer Look

In the new study, Herman and his colleagues used data from a large study known as TRIAD, identifying  786 cases of fractures and comparing them to 2,657 patients who had diabetes but no fracture history.

Of the 786 patients with fractures, only 54 were women less than 50 years old, while 457 were women 50 and older and 275 were men.

The researchers looked at prescriptions participants had filled during the 90 days prior to the fracture date or 90 days before a designated study date for those without fractures.

The finding that women with fractures were much more likely to be taking a TZD drug held for both Avandia and Actos, they found. "So it seems to be a class effect," Herman says.

The higher the dose, the higher the fracture risk, they found.

Among the men, only those taking a TZD along with a potent diuretic, called a loop diuretic, were more likely to have a fracture. Taking TZD alone did not appear to increase risk in men.

Loop diuretics have been linked with bone density decreases, Herman says.

Why the TZD drugs boost fracture risk may be due to effects such as the reduction of new bone formation or increased bone breakdown, he says.

The fractures found, he says, ''are not typical osteoporosis fractures," which include those of the spine and hip. They found some spine and hip fractures, but also many lower limb, arm, and leg fractures.

The study was funded by the CDC and the National Institute of Diabetes and Digestive and Kidney Diseases. Herman has served as a consultant for GlaxoSmithKline, which makes Avandia.