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

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.

Keywords: Bone microarchitecture; Bone turnover; Hemoglobin A1C; Type 2 diabetes mellitus.

Conflict of interest statement

Declarations

Conflict of interest 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.

© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Figures

Fig. 1

Medication regimens of the study participants. DPP4i dipeptidyl peptidase 4 inhibitor, SU Sulfonylurea, Met Metformin, TZD Thiazolidinedione, GLP-1 Glucagon-like peptide-1 receptor agonists, SGLTi sodium-glucose cotransporter-2 inhibitors

Fig. 2

Serum osteocalcin (OCN) and C-terminal telopeptide (CTx) Concentrations at − 12 Month. 2A: OCN by A1C group. 2B: CTx by A1C group. − 12 Month: 12 months prior to study enrollment. Groups were defined as: 1) no T2DM, 2) T2DM with A1C ≤ 7%, and 3) T2DM with A1C > 7%. Superscripts refer to post-hoc analyses, indicating that the value is: a) p < 0.05 compared to group 1, and b) p < 0.05 compared to group 2

Fig. 3

Stiffness and Failure Load at the Tibia at − 12 Month. 3A: Stiffness by A1C group. 3B: Failure load by A1C group. − 12 Month: 12 months prior to study enrollment. Groups were defined as: 1) no T2DM, 2) T2DM with A1C ≤ 7%, and 3) T2DM with A1C > 7%. Superscripts refer to post-hoc analyses, indicating that the value is: a) p < 0.05 compared to group 1, and b) p < 0.05 compared to group 2