Thiazolidinediones: New Evidence of Bone Loss

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The thiazolidinediones (TZDs) improve insulin sensitivity and are widely prescribed for treatment of type 2 diabetes. Rosiglitazone and pioglitazone, the two TZDs currently approved for clinical use, have been available since 1999. Troglitazone became available in 1997 but was withdrawn in 2000 due to rare cases of liver toxicity. The TZDs have been extensively studied as a treatment for diabetes and have been shown to reduce progression to diabetes in those with impaired glucose metabolism. Although animal models and observational data in humans indicate that TZDs may cause reduced bone formation and bone loss (1, 2), little is known about the clinical effects of these hypoglycemic medications on the skeleton. In this issue, Grey et al. (3) provide the first evidence from a randomized trial that rosiglitazone causes bone loss. The trial enrolled healthy postmenopausal women who did not have diabetes or osteoporosis. After 14 wk of treatment with rosiglitazone, participants experienced a significant decrease in bone density (−1.9% rosiglitazone vs. −0.2% placebo) at the total hip accompanied by a modest reduction (−8 to −13%) in bone formation markers without a change in resorption markers.