The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial

J Clin Endocrinol Metab. 2007 Apr;92(4):1305-10. doi: 10.1210/jc.2006-2646. Epub 2007 Jan 30.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone Density / drug effects*
  • Bone Density Conservation Agents / therapeutic use*
  • Bone and Bones / drug effects
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • PPAR gamma / agonists*
  • Placebos
  • Postmenopause
  • Rosiglitazone
  • Thiazolidinediones / therapeutic use*


  • Bone Density Conservation Agents
  • Hypoglycemic Agents
  • PPAR gamma
  • Placebos
  • Thiazolidinediones
  • Rosiglitazone