The study by Douglas and colleagues adds to an emerging body of observational data which suggests that the increase in fracture risk caused by thiazolidinediones (TZDs) applies throughout the skeleton, and to men as well as women. The authors state that the mechanism of TZD-induced skeletal fragility in not known. In fact, data from both preclinical and clinical studies demonstrate that TZDs decrease bone formation and maintain inappropriately normal levels of bone resorption by activating the gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) in mesenchymal stem cells and osteoclast precursors [1]. These effects on bone remodeling, which are similar to those that underpin glucocorticoid-induced skeletal toxicity [2], promote accelerated bone loss [3]. Physicians should assess fracture risk in individuals for whom TZD therapy is being considered [4], and prescribe alternative hypoglycemic therapies to those at moderate to high risk.

1. Grey A (2009) Thiazolidinedione-induced skeletal fragility; mechanisms and implications. Diabetes Obesity Metab 11: 275-284.
2. Reid IR (1997) Glucocorticoid osteoporosis--mechanisms and management. Eur J Endocrinol 137: 209-217.
3. Grey A, Bolland M, Gamble G, Wattie D, Horne A, et al. (2007) The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: A randomized, controlled trial. J Clin Endocrinol Metab 92: 1305-1310.
4. FRAX: WHO fracture risk assessment tool. http://www.shef.ac.uk/FRA...