OR23-07 Association of Insulin-Resistance and Fracture Risk in the MrOS cohort

Abstract Disclosure: J. Ha: None. L. Lui: None. K.E. Ensrud: None. Q. Xiao: None. A.R. Hoffman: None. J.Y. Wu: None. Background: Insulin resistance (IR) is closely associated with chronic conditions such as type 2 diabetes and hypertension (1). However, its impact on bone health, particularly fracture risk, remains controversial. Notably, IR is more prevalent in men than women, yet its relationship with fracture risk in male populations is unknown. This study aimed to evaluate the association between IR, estimated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and the Triglyceride-Glucose (TyG) index, and fracture risk in older men within the MrOS cohort. Methods: Data from the MrOS cohort, consisting of 5,994 men aged 65 years and older, were analyzed to evaluate the association between insulin resistance (HOMA-IR, TyG index) and fracture risk. A total of 5,416 participants were included in the HOMA-IR analysis, and 5,384 participants were included in the TyG index analysis. Participants were grouped into quartiles based on insulin resistance indices, and fracture outcomes, including any fracture, hip fracture, clinical vertebral fracture, and major osteoporotic fracture (MOF) were evaluated during follow-up. The mean follow-up times were 12.2 years for any fracture, 13.6 years for hip and vertebral fractures, and 13.1 years for MOF. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals with quartile 1 (Q1) as the reference group. Models were adjusted for age, body mass index, prevalent fracture, smoking, cancer, rheumatoid arthritis, corticosteroid, anti-osteoporosis medication, total hip bone mineral density. Results: Baseline characteristics differed significantly across quartiles of HOMA-IR and TyG index. Participants in the highest quartile (Q4) were younger and exhibited more adverse metabolic profiles, including higher BMI and glucose levels, compared to those in lower quartiles. Neither HOMA-IR nor TyG index were related to risk of hip or vertebral fractures. In the HOMA-IR analysis, men in quartile 3 (Q3) compared to those in Q1 had a significantly lower hazard ratio (HR) for any fracture (multivariable-adjusted HR 0.82, 95% CI 0.70-0.97). Similarly, men in Q3 vs Q1 of TyG index had lower risks of any and MOF (adjusted HRs 0.84 (95% CI 0.72-0.98) for any fracture and 0.80 (95% CI 0.65-0.99) for MOF). In the sensitivity analysis excluding participants with diabetes, the associations observed in Q3 remained robust. Conclusion: Older community dwelling men in Q3 of HOMA-IR and TyG indices compared with those in Q1 had modest reductions in risks for any fracture and MOF. However, these significant associations were not consistently observed across other quartiles or fracture types. Further studies are needed to confirm these findings and determine their clinical implications in older men. Reference: (1) : Nutr Metab Cardiovasc Dis, 2022. 32(3): p. 596-604. Presentation: Sunday, July 13, 2025