ORF43-05 - The Association between Hemoglobin A1c and Vertebral Bone Strength in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Hyperglycemia negatively impacts both osteocyte and osteoblast function, leading to lower bone formation and higher bone resorption, potentially affecting bone strength. Biomechanical computed tomography (BCT) is an advanced analysis of CT scans that estimates vertebral bone strength; however, there are limited data evaluating the relationship between HbA1c, a marker of glycemia, and BCT-based bone strength.

Methods: This cross-sectional study used Year 25 CARDIA data in participants with abdominal CT scans. HbA1c, assessed using standard assays, was analyzed continuously and categorically ( < 5.7%; 5.7% – < 6.5%; ≥6.5%). BCT analysis of the third lumbar body was performed to provide measurement of total strength, volumetric BMD (vBMD; total, cortical, mid-vertebral), and vertebral body area (VBA). Multivariable linear regression was used to evaluate the associations between HbA1c and BCT outcomes, adjusting for age, sex, race, height, weight, and significant socioeconomic, anthropometric, lifestyle, comorbidities, and medication variables. Effect modification by sex, age, race, dyslipidemia, estimate glomerular filtration rate (eGFR), and menopausal status in women was evaluated using (significance p< 0.1).

Results: The analytic sample (n = 2,739) had a mean (IQR) age of 50.1 (43 - 55) years; 50.6% were Black race, and 63.8% were women. Most participants had HbA1c < 5.7% (68.5%), whereas 8.6% had HbA1c ≥6.5%. There were no significant associations between HbA1c as a continuous variable and the BCT variables after adjustment. After full adjustment, mid-vertebral vBMD was the only BCT measure significantly associated with HbA1c; participants with HbA1c ≥6.5% had higher mid-vertebral vBMD compared to those with normal glycemia (β = 5.76 mg/cm3, p = 0.047). Significant sex interactions were found with cortical vBMD differed by sex (p = 0.056); higher HbA1c was associated with lower cortical vBMD in women (β = -1.58 mg/cm3, p = 0.296) but not in men (β = 0.86 mg/cm3, p = 0.536). Significant race interactions were observed for VBA (p = 0.052); higher HbA1c was associated with lower VBA in Blacks (≥6.5%: β = -0.25 cm2, p = 0.071) but not Whites (≥6.5%: β = 0.11 cm2, p = 0.607). Dyslipidemia also modified the association with total strength (p=0.056); higher HbA1c was associated with lower strength (β = -153.6 newtons, p = 0.111) in those without dyslipidemia but not in those with dyslipidemia (β = 6.72, p = 0.926). Age, eGFR, and menopausal status were not significant effect modifiers.

Conclusions: In this cohort of middle-aged US adults unselected for diabetes status, higher HbA1c was associated with higher mid-vertebral vBMD, and there were suggestions that sex, race, and dyslipidemia modified the relationship; however, the individual associations were not significant when stratified. Future research is needed to understand the pathways linking glycemia and bone strength.