The finding comes from Swiss researchers who analyzed 12 years of data on U.K. diabetes patients. They compared the 1,020 patients who suffered some kind of fracture to 3,728 matched patients who did not break any bones.
Over the course of the study, most of the patients took several diabetes drugs. But those who refilled their Actos or Avandia prescriptions eight times or more -- about 12 to 18 months of use -- had nearly twice the fracture risk of other patients.
And those who refilled their Actos or Avandia prescriptions 15 times or more -- two or more years of treatment -- nearly tripled their risk of fracture, found Christophe R. Meier, PhD, head of pharmacoepidemiology research at University Hospital Basel, Switzerland, and colleagues.
"We found a very strong signal here for higher risk of fractures in people taking glitazones," Meier tells WebMD. "Our evidence fits together nicely with animal models and clinical reports suggesting that these drugs have a detrimental effect on bone. And we did not find any increased risk for other diabetes drugs, so all together, it looks like something really is going on here."
Animal studies reported late last year strongly suggest that Actos and Avandia promote bone loss. Signs that women taking Avandia might be at increased risk of upper arm and hand fracture last year led the drug's manufacturer, GlaxoSmithKline, to voluntarily issue a letter warning doctors that Avandia might increase fracture risk.
The Meier study, all by itself, looked at too few patients to prove anything. But University of Pittsburgh researcher Jane A. Cauley, DrPH, who has studied bone loss in people with diabetes, agrees with Meier that it adds to a growing body of evidence.
"These animal and laboratory studies show these drugs interfere with the cells that grow new bone," Cauley tells WebMD. "That there is basic research supporting this study is important."
Nancy Pekarek, vice president of corporate media relations for GlaxoSmithKline, notes that Avandia already has language on its label warning users of possible fracture risk. She notes that the ADOPT clinical trial of Avandia did not detect increased hip or spine fractures, although it did find increased upper arm, hand, and foot fractures in women but not in men.
Meier, whose study showed increased fractures in both women and men, says the difference might be that patients in his study had an average age over 60, while the average age of ADOPT patients was in the mid-50s.
"Previous findings in younger individuals with fractures at the lower and upper distal limbs might reflect the kinds of fractures that younger women would tend to experience," Meier and colleagues suggest in their report.
Meier does not think either Avandia or Actos should be taken off the market. He strongly agrees with Pekarek that all drugs carry risks, including other types of diabetes drugs.
Given that Avandia has also been linked to heart risks, Cauley suggests that patients should try older diabetes drugs before trying either Avandia or Actos.
Takeda Pharmaceuticals, which makes Actos, was unable to respond to WebMD's request for comment in time for deadline.
Meier and colleagues' report, and an accompanying editorial by Cauley, appear in the April 28 issue of Archives of Internal Medicine.