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One-Year Mean A1c of > 7% is Associated with Poor Bone Microarchitecture and Strength in Men with Type 2 Diabetes Mellitus

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Abstract

Introduction

Type 2 diabetes mellitus (T2DM) is associated with normal or slightly elevated bone mineral density (BMD) but paradoxically increased fracture risk. Although multiple mechanisms have been proposed to explain this observation, one thing is clear from prior studies, T2DM is associated with poor bone quality rather than a defect in bone quantity. The objective of our study is to evaluate the effect of longitudinal glycemic control on bone quality and bone turnover in men with T2DM.

Methods

This was a secondary analysis of baseline data from 169 male participants, aged 35–65 in 3 clinical trials. Participants were grouped according to the average of all their A1C measurements between 9 and 15 months prior to study entry (group 1: no T2DM, group 2: T2DM with A1C ≤ 7%, group 3: T2DM with A1C > 7%). At study entry serum osteocalcin and C-terminal telopeptide of type 1 collagen (CTx) were measured by ELISA, and testosterone and estradiol by liquid-chromatography/mass-spectrometry. Areal BMD, trabecular bone score and body composition were measured by dual-energy X-ray absorptiometry while volumetric BMD, bone microarchitecture, and bone strength were assessed by high-resolution peripheral quantitative computed tomography.

Results

At the tibia, trabecular separation was higher and trabecular number was significantly lower in group 3 compared to both groups 2 and 1, even after adjustments for covariates (p = 0.02 for both). Bone strength indices at the tibia such as stiffness and failure load were lowest in group 3, the difference being significant when compared to group 1 (p = 0.01, p = 0.009 respectively) but not to group 2, after adjustments for covariates. Bone turnover markers (osteocalcin and CTx) were significantly lower in group 3 relative to group 1, with CTx also being significantly lower in group 3 compared with group 2 (p < 0.001, p = 0.001 respectively).

Conclusion

Poor glycemic control over the course of a year in men with T2DM is associated with poorer bone microarchitecture and strength, and reduced bone turnover. Conversely, good glycemic control in the setting of T2DM appears to attenuate this observed impairment in bone quality.

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Acknowledgements

This work was conducted using the facilities at the Michael E. DeBakey VA Medical Center, Houston, TX, USA and the Center for Translational Research in Inflammatory Diseases at the Michael E. DeBakey VA Medical Center, Houston, TX, Alkek Foundation. Additional support was provided by staff at Baylor College of Medicine.

Funding

This work was supported by the National Institutes of Health (Grant No. 5R01HD093047-02) and the VA Merit Review (1I01CX001665-01A2).

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Elliot Ballato, F. N. U. Deepika, Vittoria Russo, Alcibiades Fleires-Gutiérrez, Georgia Colleluori, Virginia Fuenmayor, Rui Chen, Dennis T. Villareal & Reina Armamento-Villareal

  2. Center for Translational Research on Inflammatory Disease, Michael E DeBakey VA Medical Center, Houston, TX, USA

    Elliot Ballato, F. N. U. Deepika, Alcibiades Fleires-Gutiérrez, Georgia Colleluori, Virginia Fuenmayor, Rui Chen, Dennis T. Villareal & Reina Armamento-Villareal

  3. Biomedical Research Institute of New Mexico, Albuquerque, NM, USA

    Clifford Qualls

  4. New Mexico VA Health Care System, Albuquerque, NM, USA

    Clifford Qualls

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  1. Elliot Ballato
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  2. F. N. U. Deepika
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Correspondence to Reina Armamento-Villareal.

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Elliot Ballato, F. N. U. Deepika, Vittoria Russo, Alcibiades Leonardo Fleires Gutierrez, Georgia Colleluori, Virginia Fuenmayor, Rui Chen, Dennis T. Villareal, Clifford Qualls, and Reina Armamento-Villareal of this work have no conflicts of interest to declare.

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Ballato, E., Deepika, F.N.U., Russo, V. et al. One-Year Mean A1c of > 7% is Associated with Poor Bone Microarchitecture and Strength in Men with Type 2 Diabetes Mellitus. Calcif Tissue Int 111, 267–278 (2022). https://doi.org/10.1007/s00223-022-00993-x

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