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The Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone Increases Bone Resorption in Women with Type 2 Diabetes: A Randomized, Controlled Trial

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Abstract

In previous studies, with up to 16 weeks of exposure to rosiglitazone or pioglitazone, circulating markers of bone formation [procollagen I N-terminal propeptide (P1NP), osteocalcin, and bone-specific alkaline phosphatase] decreased but no change in bone resorption markers was found. We examined the effect of rosiglitazone on bone resorption and formation markers when used for 24 weeks. This post-hoc analysis of a double-blind, placebo-controlled, randomized trial evaluated the effects of 6 months of rosiglitazone use versus placebo on circulating markers of bone turnover in 111 patients with type 2 diabetes and cardiovascular disease or additional cardiac risk factors. The principal end points for analysis were changes in bone formation and resorption markers, measured by P1NP and carboxy-terminal cross-links (CTX), respectively. There were 111 subjects who completed the study and had baseline and 6-month data; mean age was 56, including 41% women and 67% nonwhite (50 black, 18 Hispanic, and six other), and subjects were evenly distributed between placebo and rosiglitazone groups. Women treated with rosiglitazone had higher CTX levels (0.43 ng/mL) than those who received placebo (0.23 ng/mL) (P = 0.007), with no significant differences in P1NP or OPG. Overall, in stratified analyses of men and in stratified analyses among different ethnicities, there were no statistically significant differences observed in CTX, P1NP, OPG, PTH, or 25-OHD between the treatment groups. Women taking rosiglitazone had higher circulating markers of bone resorption, which is contrary to prior studies of shorter duration, where the principal observation was a decrease in markers of bone formation.

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Acknowledgement

This work was supported by grants from GlaxoSmithKline, Biosite, and the Donald W. Reynolds Foundation.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA

    Ugis Gruntmanis, Steve Fordan & Hans K. Ghayee

  2. Division of Cardiology, University of Texas, Southwestern Medical Center, Dallas, TX, 75390, USA

    Shuaib M. Abdullah, Colby R. Ayers & Darren K. McGuire

  3. Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas, Southwestern Medical Center, Dallas, TX, 75390, USA

    Colby R. Ayers & Darren K. McGuire

  4. Section of Endocrinology, Dallas Veterans Affairs Medical Center, Dallas, TX, 75216, USA

    Ugis Gruntmanis

  5. Division of Cardiology, Vanderbilt University, Nashville, TN, 37212, USA

    Raphael See

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  1. Ugis Gruntmanis
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  2. Steve Fordan
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  7. Darren K. McGuire
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Correspondence to Ugis Gruntmanis.

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Ugis Gruntmanis, Steve Fordan contributed equally to this work.

U. G. has received research support from Procter & Gamble, Novartis, GlaxoSmithKline, and Amgen. D. K. M. was previously on speakers’ bureaus for Takeda and Pfizer and is a consultant with Novo Nordisk, Johnson and Johnson, and Tethys Bioscience. All other authors have no conflict of interest.

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Gruntmanis, U., Fordan, S., Ghayee, H.K. et al. The Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone Increases Bone Resorption in Women with Type 2 Diabetes: A Randomized, Controlled Trial. Calcif Tissue Int 86, 343–349 (2010). https://doi.org/10.1007/s00223-010-9352-5

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  • DOI: https://doi.org/10.1007/s00223-010-9352-5

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