Thiazolidinediones and fracture risk in patients with Type 2 diabetes

Thiazolidinediones are widely used effective drugs for the management of hyperglycaemia in Type 2 diabetes and may provide additional metabolic benefits. Any advantages of these agents need to be considered in the context of any potential risk from adverse events. Recent evidence from several sources, including large-scale randomized controlled trials and observational studies, suggests that long-term use of thiazolidinediones is associated with bone loss and an increased risk of fractures in women with Type 2 diabetes. As patients with Type 2 diabetes are already at high risk for fractures, the clinical relevance of this reported association with thiazolidinedione therapy deserves careful consideration. Generally, the fracture risk with thiazolidinediones appears similar in magnitude to that associated with several other widely used drug classes, although there are unanswered questions regarding susceptibility factors, differential effects on bone sites and potential management approaches. This article provides a comprehensive overview of the evidence for an increase in fracture risk with thiazolidinediones and places it in the context of recent analyses of fracture risk with other commonly used drug classes. The potential clinical implications of any association are also discussed.