Rosiglitazone Decreases Bone Mass and Bone Marrow Fat

Abstract

Activation of peroxisome proliferator-activated receptor-γ is believed to promote adipocyte development from mesenchymal stem cells in the bone marrow at the expense of osteoblasts, leading to decreased bone mineral density (BMD) and increased marrow fat. The objective of the study was to examine the effect of the peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, on BMD assessed by dual-energy x-ray absorptiometry in 53 healthy postmenopausal women and spine bone marrow fat assessed by magnetic resonance imaging proton spectroscopy. This was a 14-wk prospective, double-blind, randomized, placebo-controlled trial. The study was conducted in the general community. Fifty-three healthy postmenopausal women participated in the study. Intervention included rosiglitazone tablets of 8 mg/d. The primary end point was a change in BMD. At the femoral neck, BMD decreased by 1.34 ± 0.60% (mean ± sem) in the rosiglitazone group, whereas BMD increased by 0.28 ± 0.56% in the placebo group (P = 0.055). At the lumbar spine, BMD decreased by 1.03 ± 0.34% in the rosiglitazone group and 0.42 ± 0.35% in the placebo group (P = 0.22). The bone resorption marker carboxy-terminal telopeptide increased by 20.4 ± 7.7% (mean ± sem) in the rosiglitazone group and decreased by 7.1 ± 4.7% in the placebo group (P = 0.003). Spine fat decreased by 13.5 ± 5.5% (mean ± sem) in the rosiglitazone group and increased by 6.8 ± 7.4% in the placebo group (P = 0.056). Contrary to what was expected, spine fat decreased during rosiglitazone treatment. Furthermore, rosiglitazone treatment resulted in uncoupling of bone resorption and formation leading to bone loss. Our data suggest that the bone marrow osteoblast-adipocyte relationship is more complex than was assumed and that the two cell types can be independently affected.