Impact of pioglitazone on bone mineral density and bone marrow fat content
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Pioglitazone use is associated with an increased risk of fractures. In this randomized, placebo-controlled study, pioglitazone use for 12 months was associated with a significant increase in bone marrow fat content at the femoral neck, accompanied by a significant decrease in total hip bone mineral density. The change in bone marrow fat with pioglitazone use was predominantly observed in female vs. male participants.
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 (45 mg/day) or matching placebo for 1 year. 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 12 months, 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 12 months 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.
KeywordsBone Marrow Fat Bone Mineral Density Fracture Pioglitazone
The authors would like to thank Madhuri Poduri, MS (Department of Internal Medicine, UTSW) for her expert help in protocol implementation, patient care, and data collection. The authors would also like to express their gratitude to all the study volunteers and UTSW Hospital Staff.
Compliance with ethical standards
This work was supported by the National Institutes of Health grants: RR024476 and RR024982.
Conflicts of interest
Ildiko Lingvay received consultant/research grants from Novo Nordisk; consultant from AstraZeneca, Lilly, and Sanofi; and research grant from GI Dynamics and Pfizer/Merck and publication support from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Sanofi. The remaining authors have nothing to disclose.
All procedures performed in the present study involving human participants were approved by the University of Texas at Southwestern Medical Center at Dallas (TX) Institutional Review Board and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants in the study.
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