Impact of pioglitazone on bone mineral density and bone marrow fat content.

Abstract

Use of the insulin sensitizer pioglitazone is associated with greater fracture incidence, although the underlying mechanisms are incompletely understood. This study aimed to assess the effect of pioglitazone treatment on femoral neck bone marrow (BM) fat content and on bone mineral density (BMD), and to establish if any correlation exists between the changes in these parameters. In this double-blind placebo-controlled clinical trial, 42 obese volunteers with metabolic syndrome were randomized to pioglitazone (45mg/day) or matching placebo for 1year. The following measurements were conducted at baseline and during the treatment: liver, pancreas, and femoral neck BM fat content (by magnetic resonance spectroscopy), BMD by DXA, abdominal subcutaneous and visceral fat, and beta-cell function and insulin sensitivity. Results were available for 37 subjects who completed the baseline and 1-year evaluations. At 12months, BM fat increased with pioglitazone (absolute change, +4.1%, p=0.03), whereas BM fat content in the placebo group decreased non-significantly (-3.1%, p=0.08) (p=0.007 for the pioglitazone-placebo response difference). Total hip BMD declined in the pioglitazone group (-1.4%) and increased by 0.8% in the placebo group (p=0.03 between groups). The change in total hip BMD was inversely and significantly correlated with the change in BM fat content (Spearman rho = -0.56, p=0.01) in the pioglitazone group, but not within the placebo group (rho = -0.29, p=0.24). Changes in BM fat with pioglitazone were predominantly observed in female vs. male subjects. Pioglitazone use for 12months compared with placebo is associated with significant increase in BM fat content at the femoral neck, accompanied by a small but significant decrease in total hip BMD.