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Published on: April 14, 2016
TZDs and Bone: A Review of the Recent Clinical Evidence
1Department of Epidemiology and Biostatistics, University of California San Francisco, 185 Berry Street, Suite 5700, San Francisco, CA 94107, USA.
Abstract:
Over the past two years, evidence has emerged that the currently available thiazolidinediones (TZDs), rosiglitazone, and pioglitazone have negative skeletal consequences, at least in women, which are clinically important. Increased fracture risk in women, but not men, was reported for both TZDs, based on analyses of adverse event reports from clinical trials. In short-term clinical trials in women, both TZDs caused more rapid bone loss. In these trials, changes in bone turnover markers suggest a pattern of reduced bone formation without a change in resorption. Although limited, these results support the hypothesis based on rodent and in vitro models that reduced bone formation resulting from activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) is a central mechanism for TZDs' effect on bone. Research is needed to better understand the mechanisms of bone loss with TZDs, to identify factors that influence susceptibility to TZD-induced osteoporosis, and to test treatments for its prevention.
Insights
Thiazolidinediones (TZDs) like rosiglitazone and pioglitazone increase fracture risk and bone loss in women. This may be due to reduced bone formation linked to PPARgamma activation.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Bone Biology
Background:
- Thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, are antidiabetic medications.
- Emerging evidence suggests TZDs may have adverse skeletal effects, particularly in women.
Purpose of the Study:
- To summarize the evidence on the skeletal consequences of TZDs.
- To explore the potential mechanisms behind TZD-induced bone loss.
Main Methods:
- Analysis of adverse event reports from clinical trials.
- Review of short-term clinical trial data in women.
- Examination of bone turnover markers.
Main Results:
- Increased fracture risk in women, but not men, associated with both rosiglitazone and pioglitazone.
- Accelerated bone loss observed in women during short-term trials.
- Bone turnover markers indicated reduced bone formation without altered resorption.
Conclusions:
- TZDs may negatively impact bone health, especially in women.
- Reduced bone formation, potentially mediated by peroxisome proliferator-activated receptor-gamma (PPARgamma) activation, is a likely mechanism.
- Further research is needed to understand TZD-induced osteoporosis and its prevention.
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