Pioglitazone increases bone marrow fat in type 2 diabetes: results from a randomized controlled trial

Objective: To determine the effect of pioglitazone on bone marrow fat in humans. Design: Twenty participants in a double-blind, randomized, placebo-controlled trial of the skeletal effects of pioglitazone 30 mg daily in type 2 diabetes mellitus (T2DM) entered a 6-month substudy evaluating bone marrow fat. Main outcome measures were bone marrow fat in lumbar spine (L4) and proximal femur (intertrochanteric region), measured using magnetic resonance (MR) imaging, and bone mineral density (BMD), measured using dual-energy X-ray absorptiometry. Results: After 6 months, change in the fourth lumbar vertebra (L4) bone marrow lipid fraction, assessed using two different methods, was greater in the pioglitazone group than in the placebo group (Dixon method: mean (95% CI) change from baseline pioglitazone 1.3% (-0.3, 2.9), placebo -0.2% (-0.8, 0.4), P=0.06; MR spectroscopy: pioglitazone 2.5% (0.4, 4.7), placebo -1.1% (-3.7, 1.4), P=0.02). Similarly, the change in lipid fraction in the intertrochanteric region was greater in the pioglitazone group (Dixon method: mean (95% CI) change from baseline pioglitazone 1.3% (0.6, 1.9), placebo -0.8% (-1.8, 0.2), P=0.001). Within the pioglitazone group, there was no evidence of a significant relationship between change in marrow lipid fraction and BMD. Conclusions: Short-term treatment with pioglitazone increases bone marrow fat in patients with T2DM.