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

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.

Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus.

Background: Emerging data suggest that type 2 diabetes mellitus (T2D) is associated with an increased risk for fractures despite relatively normal or increased bone mineral density (BMD). Although the mechanism for bone fragility in T2D patients is multifactorial, whether glycemic control is important in generating this impairment in bone metabolism remains unclear. The purpose of our study is to identify a hemoglobin A1c (A1c) threshold level by which reduction in bone turnover begins in men with T2D. Method: A cross-sectional analysis of baseline data was obtained from 217 men, ages 35-65, regardless of the presence or absence of hypogonadism or T2D, who participated in 2 clinical trials. The following data were obtained: A1c by HPLC, testosterone and estradiol by LC/MS, bone turnover markers Osteocalcin [OC], C-terminal telopeptide [CTx], and sclerostin by ELISA, and BMD by DXA. Patients were grouped into 4 categories based of A1c (group I: <6%, group II: 6.0-6.4%, group III: 6.5-6.9%, and group IV: ≥7%). Threshold models were fit to the data using nonlinear regression and group comparisons among the different A1c categories performed by ANOVA. Results: Threshold model and nonlinear regression showed an A1c cut-off of 7.0, among all choices of A1cs, yields the least sum of squared errors. A comparison of bone turnover markers revealed relatively lower OC (p = 0.002) and CTx (p = 0.0002) in group IV (A1c ≥7%), compared to the other groups. An analysis of men with T2D (n = 94) showed relatively lower OC (p=0.001) and CTx (p=0.002) in those with A1c ≥7% compared to those with <7%, respectively. The significance between groups persisted even after adjusting for medications and duration of diabetes. Conclusion: An analysis across our entire study population showed a breakpoint A1c level of 7% or greater is associated with lower bone turnover. Also in men with T2D, an A1c ≥7% is associated with low bone turnover.