FRACTURES AND " GLITAZONES " .

" Glitazones " are a group of drugs that we use to treat Type 2 Diabetes. They belong to a family of drugs called " ppar gamma " agonist. There are two drugs comercially available in the market namely rosiglitazones ( Avandia-GSK ) and pioglitazone ( Actos-Takeda ). They were both FDA approved. If you remember, about 5 years ago, there was this hooha about the glitazones being associated with an increase risk of CV events? This was highly controversial and many of us still use it with caution. But eversince the release of the results of ADOPT and RECORD, there was a high index of suspicion that " Glitazones " may increase the incidence of fractures. In fact, FDA required the companies to put in a labelling warning of the risk of fractures. At that time, some did not agree and felt that the fracture risk was minimal and may not be due to the drug.
In the 10th August issue of the Archives of Internal Medicine, workers in University of British Columbia, Vancouver, led by Dr Colin Dormuth, published an observational study of follow ups in 84,000 patients on the glitazones for at least 3 years duration and found that there was a 28% increase incidence of peripheral fractures in the long bones of their patients, there was minimal difference in the fracture incidence between pioglitazone ( slightly more ) and rosiglitazone. There was also no difference in the incidence between the sexes, although it was earlier believed that females were more prone. When they work out the statistics, for every 84 patients treated with the glitazones for 3 years, 1 may result in a fracture. Although it is not alot, it is worrying as these patients have diabetes and are usually in the older age group. adding another co-morbidity certainly does not help.
It is interesting to spectculate on the reason for this, although no one actually know. The ppar agonist ligand is involved in cell metabolism and protein formation. I really do not know the connection between the glitazones and bone matrix and calcium metabolism.
I have quite a few patients on rosiglitazone and so I must warn them that the evidence is stronger now that rosiglitazones may increase their risk of fractures.