CONTEXT: Thiazolidinediones, which are peroxisome proliferator-activated receptor-gamma agonists, are widely prescribed to patients with disorders characterized by insulin resistance. Preclinical studies suggest that peroxisome proliferator-activated receptor-gamma signaling negatively regulates bone formation and bone density. Human data on the skeletal effects of thiazolidinediones are currently available only from observational studies. OBJECTIVE: The objective of the study was to determine whether rosiglitazone, a thiazolidinedione, inhibits bone formation. DESIGN: The study was a 14-wk randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted in the general community. PATIENTS: Fifty healthy, postmenopausal women participated in the study. INTERVENTION: Intervention was rosiglitazone 8 mg/d. MAIN OUTCOME MEASURES: The primary end point was biochemical markers of bone formation, and secondary end points were a bone resorption marker and bone mineral density. RESULTS: The osteoblast markersprocollagen type I N-terminal propeptide and osteocalcin declined by 13% (P<0.005 vs. placebo) and 10% (P=0.04 vs. placebo), respectively, in the rosiglitazone group. These changes were evident by 4 wk and persisted for the duration of the study. There was no change in the serum beta-C-terminal telopeptide of type I collagen, a marker of bone resorption (P=0.9 vs. placebo). Total hip bone density fell in the rosiglitazone group (mean change from baseline rosiglitazone -1.9%, placebo -0.2%; between-group difference 1.7%, 95% confidence interval 0.6-2.7, P<0.01); lumbar spine bone density fell significantly from baseline values in the rosiglitazone group (P=0.02 vs. baseline) but was not significantly different between groups (mean change from baseline rosiglitazone -1.2%, placebo -0.2%; between-group difference 1.0%, 95% confidence interval -0.2-2.3, P=0.13). CONCLUSIONS: Short-term therapy with rosiglitazone exerts detrimental skeletal effects by inhibiting bone formation. Skeletal end points should be included in future long-term studies of thiazolidinedione use.
RCT Entities:
CONTEXT: Thiazolidinediones, which are peroxisome proliferator-activated receptor-gamma agonists, are widely prescribed to patients with disorders characterized by insulin resistance. Preclinical studies suggest that peroxisome proliferator-activated receptor-gamma signaling negatively regulates bone formation and bone density. Human data on the skeletal effects of thiazolidinediones are currently available only from observational studies. OBJECTIVE: The objective of the study was to determine whether rosiglitazone, a thiazolidinedione, inhibits bone formation. DESIGN: The study was a 14-wk randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted in the general community. PATIENTS: Fifty healthy, postmenopausal women participated in the study. INTERVENTION: Intervention was rosiglitazone 8 mg/d. MAIN OUTCOME MEASURES: The primary end point was biochemical markers of bone formation, and secondary end points were a bone resorption marker and bone mineral density. RESULTS: The osteoblast markers procollagen type I N-terminal propeptide and osteocalcin declined by 13% (P<0.005 vs. placebo) and 10% (P=0.04 vs. placebo), respectively, in the rosiglitazone group. These changes were evident by 4 wk and persisted for the duration of the study. There was no change in the serum beta-C-terminal telopeptide of type I collagen, a marker of bone resorption (P=0.9 vs. placebo). Total hip bone density fell in the rosiglitazone group (mean change from baseline rosiglitazone -1.9%, placebo -0.2%; between-group difference 1.7%, 95% confidence interval 0.6-2.7, P<0.01); lumbar spine bone density fell significantly from baseline values in the rosiglitazone group (P=0.02 vs. baseline) but was not significantly different between groups (mean change from baseline rosiglitazone -1.2%, placebo -0.2%; between-group difference 1.0%, 95% confidence interval -0.2-2.3, P=0.13). CONCLUSIONS: Short-term therapy with rosiglitazone exerts detrimental skeletal effects by inhibiting bone formation. Skeletal end points should be included in future long-term studies of thiazolidinedione use.
Authors: S Benvenuti; I Cellai; P Luciani; C Deledda; S Baglioni; C Giuliani; R Saccardi; B Mazzanti; S Dal Pozzo; E Mannucci; A Peri; M Serio Journal: J Endocrinol Invest Date: 2007-10 Impact factor: 4.256