TORONTO - A controversial class of Type 2 diabetes drugs seems to double the risk of bone fractures among women who take them, a study published Wednesday suggests.
The authors said doctors should reconsider using these drugs - sold as Avandia and Actos - in women with Type 2 diabetes, given this finding and a previously reported increased risk of heart failure among people who take the drugs.
Though earlier studies have shown signs the drugs seem to increase fracture rates among women who use them, this one - published online by the Canadian Medical Association Journal - is the first to quantify just how large that effect is.
It means that one fracture attributable to the drugs will occur for every 20 women aged 55 who take one of the drugs for a year and who would otherwise be at low risk of having a fracture, said Dr. Sonal Singh, an internal medicine specialist at Wake Forest University Baptist Medical Center.
"That is a substantial risk," said Singh, who wrote the study with colleagues from Wake Forest University, in Winston-Salem, N.C., and from the University of East Anglia, in Norwich, England.
"I think there's genuine scientific consensus that these risks might really outweigh benefits in Type 2 diabetes."
The drugs in question are rosiglitizone (Avandia) and pioglitazone (Actos), both from a class of drugs known as thiazolidinediones or TZDs. They are used to control blood sugar in people who develop Type 2 diabetes.
Earlier studies showed Avandia - once a blockbuster - may raise the risk of heart attacks and heart-related deaths in people who use it.
Canadian and U.S. drug regulatory agencies issued warnings about the medication and the American Diabetes Association recently said patients should avoid using it until questions about its safety have been resolved.
The earlier studies also show signs of increased rates of bone fractures among women users. So Singh and his co-authors pooled and re-analyzed data from 12 previous studies of the drugs to see if they could get a clearer picture of the risk.
In addition to doubling the risk of fractures, use of the drugs was linked to significant changes in bone mineral density at the lumbar spine and the hip.
There is no clear evidence that other drugs used to lower blood glucose levels increase the risk of bone fractures. And the researchers found no increase in bone fractures in men using the TZD drugs.
"This paper establishes what we already suspected from the individual published studies," Dr. David Nathan, a diabetes expert from Massachusetts General Hospital and Harvard school of medicine said in an email Tuesday.
"Specifically, the TZDs as a class increase the fracture risk in the part of the population that is at greatest risk, women. Whether longer-term term use of TZDs than was included in the studies might cause an even higher risk in women, and affect men as well, is not known at this time."
A commentary written for the journal by Dr. Lorraine Lipscombe of the Toronto-based Institute for Clinical Evaluative Sciences said at this point the net benefit of treatment with the drugs is unclear.
"Given that there are other effective drugs to control glycemia (blood sugar) that are associated with fewer adverse events, thiazolidinediones should not be considered appropriate as first-line therapy for Type 2 diabetes mellitus," Lipscombe wrote, adding the risk-benefit balance might shift for patients who are unable to take the other available drugs.
