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Pioglitazone and Rosiglitazone doubles risk of fractures in women with type 2 diabetes mellitus


Long-term use of glitazones, oral diabetic drugs, doubles the risk of fractures in women with type 2 diabetes. The findings are published in the Canadian Medical Association Journal ( CMAJ ).
In absolute terms, if glitazones are used by elderly, postmenopausal women ( around 70 years ) with type 2 diabetes for one year, one additional fracture would occur among every 21 women. Among younger women ( around 56 years ), use of the drugs for one year or longer would result in one additional fracture for every 55 women.

Glitazones, also known as thiazolidinediones, are oral medications given to control diabetes by lowering blood sugar. The two currently available drugs in this class are Rosiglitazone ( Avandia ), and Pioglitazone ( Actos ).

For the study, Researchers reviewed 10 previously completed trials that lasted at least one year. All of the studies included participants with impaired glucose tolerance and type 2 diabetes, and all compared the risk of fracture among patients with type 2 diabetes who were taking glitazones therapy and patients not taking the therapy. Nearly 14,000 participants were included in the studies. Data was broken down by gender in five of the studies.

Overall, the results showed that use of glitazones significantly increased the risk of fractures among patients with type 2 diabetes mellitus and was associated with changes in bone mineral density at the lumbar spine and the hip.

Data from the studies that reported sex-specific results showed that glitazones significantly increased the risk of fractures among women. They were not, however, associated with the same increase of fracture risk in men. The studies also showed a consistent decline in bone mineral density in women exposed to therapy with glitazones.

In 2006, there were nearly 4 million patients in the United States taking glitazones, half of whom were likely women.

While the underlying cause for the sex-specific effect of glitazones needs further investigation, Researchers suggest that the drugs may cause fractures by replacing bone marrow with fat cells.

Other recent studies of glitazones have focused on the adverse cardiovascular effects of Pioglitazone and Rosiglitazone.

In the June 2007 issue of Diabetes Care, Singh and colleagues reported that glitazones doubled the risk of congestive heart failure in patients with type 2 diabetes. They also reported in The Journal of the American Medical Association ( JAMA ) that use of Rosiglitazone was associated both with increased myocardial infarctions and a doubling of heart failure.

According to Authors, the relatively modest benefits of thiazolidinediones must be balanced against their significant long-term effects on bone and the cardiovascular system.

Clinicians should consider the updated 2008 guidelines of the American Diabetes Association and European Association for Study of Diabetes consensus recommendations, which do not consider glitazones among the well-validated core therapies for type 2 diabetes and uniformly advised against the use of Rosiglitazone.

Source: Wake Forest University Baptist Medical Center, 2008

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