Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men.

C ase-control studies of patients with fractures have found that subjects with diabetes have at least a twofold higher risk of fracture than subjects without diabetes (1), with an increased risk of hip, humerus, and foot fractures in elderly diabetic subjects (2–4). Risk factors that contribute to increased fracture in diabetic subjects include number of falls (5,6), insulin use (7,8), functional disability (9–11), diabetes duration (7,12), and poor vision (7). Recent studies report that older women and African Americans have higher incidence of osteoporotic fractures (13). In addition, lower bone strength (bone mineral density [BMD]) might be expected to increase risk for the development of osteoporosis and fracture. Type 2 diabetic patients are widely prescribed drugs called thiazolidinediones, which increase insulin sensitivity via activation of peroxisome proliferator– activated receptor (PPAR)receptors. However, it is not known whether thiazolidinedione use has any effect on bone mass and thereby increases risk of fracture in type 2 diabetic patients. In animal studies, thiazolidinedione treatment was associated with bone loss in a mouse model (14,15), which was explained by possible imbalance in bone from increased apoptotic death of osteogenic cells and diminished bone formation (15), and also in ovariectomized rats (16). Other investigators did not find bone loss in troglitazone-treated mice (17). There is limited information on the effect of thiazolidinediones on BMD in humans. A recent s tudy has sugges ted tha t thiazolidinedione use may cause bone loss in older women with type 2 diabetes (18). In the present study on 160 men with type 2 diabetes, we examined BMD in patients on rosiglitazone treatment compared with matched men with type 2 diabetes not on rosiglitazone treatment and found that rosiglitazone treatment increases bone loss in men with type 2 diabetes.