Abstract
Rosiglitazone and pioglitazone are associated with increased fracture risk in women, and, for rosiglitazone, more rapid bone loss. Negative skeletal effects of these thiazolidinediones (TZDs) have also been observed in animal and in vitro models. A central mechanism of action appears to be reduced bone formation, resulting in bone loss. The source of this reduced bone formation may be a shift in the lineage allocation of marrow stems cells away from osteoblasts and towards adipocytes, caused by activation of PPAR-γ with these TZDs. Research is needed to better understand the mechanisms of bone loss and to identify factors that influence susceptibility to TZD-induced osteoporosis. Clinicians should be aware of the potential for increased fracture risk when prescribing TZDs, particularly in postmenopausal women.