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Intensive Glycemic Control and Thiazolidinedione Use: Effects on Cortical and Trabecular Bone at the Radius and Tibia

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Abstract

Factors that contribute to bone fragility in type 2 diabetes are not well understood. We assessed the effects of intensive glycemic control, thiazolidinediones (TZDs), and A1C levels on bone geometry and strength at the radius and tibia. In a substudy of the Action to Control Cardiovascular Risk in Diabetes trial, peripheral quantitative computed tomographic (pQCT) scans of the radius and tibia were obtained 2 years after randomization on 73 participants (intensive n = 35, standard n = 38). TZD use and A1C levels were measured every 4 months during the trial. Effects of intervention assignment, TZD use, and A1C on pQCT parameters were assessed in linear regression models. Intensive, compared with standard, glycemic control was associated with 1.3 % lower cortical volumetric BMD at the tibia in men (p = 0.02) but not with other pQCT parameters. In women, but not men, each additional year of TZD use was associated with an 11 % lower polar strength strain index (SSIp) at the radius (p = 0.04) and tibia (p = 0.002) in models adjusted for A1C levels. In women, each additional 1 % increase in A1C was associated with an 18 % lower SSIp at the ultradistal radius (p = 0.04) in models adjusted for TZD use. There was no consistent evidence of an effect of intensive, compared with standard, glycemic control on bone strength at the radius or tibia. In women, TZD use may reduce bone strength at these sites. Higher A1C may also be associated with lower bone strength at the radius, but not tibia, in women.

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Acknowledgments

The ACCORD BONE ancillary study was funded by a grant (R01DK069514) from the National Institute of Diabetes and Digestive and Kidney Diseases. GlaxoSmithKline provided support for the pQCT substudy. The ACCORD study was supported by Grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by other components of the National Institutes of Health, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; and by General Clinical Research Centers. The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis, and Schering-Plough.

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Authors and Affiliations

  1. University of California, 185 Berry St., Suite 5700, San Francisco, CA, 94107, USA

    Ann V. Schwartz, Eric Vittinghoff, Lisa Palermo & Trisha F. Hue

  2. HealthPartners Research Foundation, Minneapolis, MN, USA

    Karen L. Margolis

  3. University of Minnesota, Minneapolis, MN, USA

    Lesley M. Scibora

  4. Wake Forest School of Medicine, Winston-Salem, NC, USA

    Walter T. Ambrosius

  5. VA Medical Center, University of Minnesota, Minneapolis, MN, USA

    Kristine E. Ensrud

Authors
  1. Ann V. Schwartz
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  2. Eric Vittinghoff
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  3. Karen L. Margolis
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  4. Lesley M. Scibora
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  5. Lisa Palermo
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  6. Walter T. Ambrosius
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  7. Trisha F. Hue
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  8. Kristine E. Ensrud
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Correspondence to Ann V. Schwartz.

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K. Ensrud has a consultant/advisory role for Merck Sharpe & Dohme. A. Schwartz has a consultant/advisory role for and has received funding from Glaxo SmithKline. L. Palermo has a consultant/advisory role for Nycomed. All other authors have stated that they have no conflict of interest.

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Schwartz, A.V., Vittinghoff, E., Margolis, K.L. et al. Intensive Glycemic Control and Thiazolidinedione Use: Effects on Cortical and Trabecular Bone at the Radius and Tibia. Calcif Tissue Int 92, 477–486 (2013). https://doi.org/10.1007/s00223-013-9703-0

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