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Submitted on November 30, 2006
Accepted on January 22, 2007
Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; LabPlus, Auckland City Hospital, Auckland, New Zealand
* To whom correspondence should be addressed. E-mail: a.gray{at}auckland.ac.nz.
Context: Thiazolidinediones, which are peroxisome-proliferator-activated receptor-gamma agonists, are widely prescribed to patients with disorders characterized by insulin resistance. Pre-clinical studies suggest that peroxisome-proliferator-activated receptor-gamma signalling negatively regulates bone formation and bone density. Human data on the skeletal effects of thiazolidinediones are currently available only from observational studies.
Objective: To determine whether rosiglitazone, a thiazolidinedione, inhibits bone formation.
Design: 14 week randomized, double-blind, placebo-controlled trial.
Setting: General community.
Patients: 50 healthy, postmenopausal women.
Intervention: Rosiglitazone 8mg/day
Main outcome measures: The primary endpoint was biochemical markers of bone formation, secondary endpoints 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 weeks, and persisted for the duration of the study. There was no change in the serum 
-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-groups difference 1.7%, 95% CI 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-groups difference 1.0%, 95%CI -0.2-2.3, p=0.13).
Conclusions: Short-term therapy with rosiglitazone exerts detrimental skeletal effects, by inhibiting bone formation. Skeletal endpoints should be included in future long-term studies of thiazolidinedione use.
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