Effects of thiazolidinediones on bone loss and fracture

OBJECTIVE: To examine the evidence regarding the effects of thiazolidinediones on bone loss and fracture. DATA SOURCES: Published studies assessing the effects of thiazolidinediones on bone and/or fracture risk in humans were selected for review. A MEDLINE (1950-April 2007) and International Pharmaceutical Abstracts (1970-April 2007) search was performed. Search terms included thiazolidinediones, rosiglitazone, pioglitazone, troglitazone, bone, bone mineral density, fracture, and osteoporosis. STUDY SELECTION AND DATA EXTRACTION: The literature search retrieved 5 English-language studies evaluating the effects of thiazolidinediones on bone in humans. These consisted of 2 small, uncontrolled studies using troglitazone; 1 prospective, randomized controlled study and 1 retrospective cohort study using rosiglitazone; and a post hoc analysis of an observational cohort study in subjects taking various thiazolidinediones. All of the studies assessed markers of bone metabolism and/or bone mineral density (BMD). No studies were identified that addressed rate of fractures in subjects taking thiazolidinediones. DATA SYNTHESIS: The first troglitazone study demonstrated a decrease in levels of bone formation markers (10%; p < 0.05) and resorption markers (12%; p < 0.01), and authors determined that troglitazone produces a protective effect on bone through decreased bone turnover. The second troglitazone study did not demonstrate a significant change in BMD or levels of bone turnover markers. The 2 rosiglitazone studies demonstrated decreases in BMD of 1.19-1.9% with rosiglitazone use (p < 0.05). The post hoc analysis with various thiazolidinediones indicated a 2.5-fold greater decrease in BMD in women reporting thiazolidinedione use. CONCLUSIONS: Few studies have assessed the effects of thiazolidinediones on bone in humans. Studies available suggest that treatment with thiazolidinediones, primarily rosiglitazone, contributes to bone loss. The effect appears to be most prominent in postmenopausal women. More studies are needed to better understand the effects of thiazolidinediones on bone and fracture rates.