Rosiglitazone decreases bone mass and bone marrow fat

Area of Science:

• Endocrinology
• Bone Biology
• Metabolic Research

Background:

• Peroxisome proliferator-activated receptor-γ (PPAR-γ) activation is linked to adipocyte development, potentially reducing bone mineral density (BMD) and increasing marrow fat.
• Mesenchymal stem cells in bone marrow may differentiate into adipocytes rather than osteoblasts under PPAR-γ activation.

Purpose of the Study:

• To investigate the effects of rosiglitazone, a PPAR-γ agonist, on BMD and bone marrow fat in postmenopausal women.
• To assess changes in BMD using dual-energy x-ray absorptiometry and spine bone marrow fat via magnetic resonance imaging proton spectroscopy.

Main Methods:

• A 14-week prospective, double-blind, randomized, placebo-controlled trial involving 53 healthy postmenopausal women.
• Participants received either 8 mg/d of rosiglitazone or a placebo.
• Primary endpoint was the change in BMD; secondary assessments included spine bone marrow fat and bone resorption markers.

Main Results:

• Rosiglitazone treatment showed a trend towards decreased BMD at the femoral neck (P=0.055) and lumbar spine (P=0.22) compared to placebo.
• Bone resorption marker (carboxy-terminal telopeptide) significantly increased with rosiglitazone (P=0.003).
• Unexpectedly, spine bone marrow fat decreased with rosiglitazone (P=0.056), contrary to initial hypotheses.

Conclusions:

• Rosiglitazone treatment led to an uncoupling of bone resorption and formation, resulting in bone loss.
• The study suggests that the relationship between bone marrow osteoblasts and adipocytes is more complex than previously assumed and they can be independently regulated.
• Findings challenge the direct link between PPAR-γ activation, increased marrow fat, and decreased BMD.