Calcified Tissue International

, Volume 92, Issue 5, pp 477–486 | Cite as

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

  • Ann V. Schwartz
  • Eric Vittinghoff
  • Karen L. Margolis
  • Lesley M. Scibora
  • Lisa Palermo
  • Walter T. Ambrosius
  • Trisha F. Hue
  • Kristine E. Ensrud
Original Research


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.


Diabetes mellitus Hemoglobin A1C Thiazolidinedione Peripheral quantitative computed tomography 



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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ann V. Schwartz
    • 1
  • Eric Vittinghoff
    • 1
  • Karen L. Margolis
    • 2
  • Lesley M. Scibora
    • 3
  • Lisa Palermo
    • 1
  • Walter T. Ambrosius
    • 4
  • Trisha F. Hue
    • 1
  • Kristine E. Ensrud
    • 5
  1. 1.University of CaliforniaSan FranciscoUSA
  2. 2.HealthPartners Research FoundationMinneapolisUSA
  3. 3.University of MinnesotaMinneapolisUSA
  4. 4.Wake Forest School of MedicineWinston-SalemUSA
  5. 5.VA Medical Center, University of MinnesotaMinneapolisUSA

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