Association of insulin resistance and fracture risk in the Osteoporotic Fractures in Men (MrOS) cohort

Context: Insulin resistance (IR) is more prevalent in men than in women, but evidence directly linking IR to fracture risk in older men remains limited. Objective: To evaluate the association between insulin resistance (IR), estimated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and the triglyceride–glucose (TyG) index, and fracture risk in older men. Methods: Data from 5994 men (≥65 years) in the MrOS cohort were analyzed. A total of 5416 participants were included in the HOMA-IR analysis and 5384 in the TyG index analysis. Fractures were self-reported and confirmed radiographically. Participants were grouped into quartiles based on IR indices, and fracture outcomes were evaluated during a mean follow-up of 12.2-13.6 years using Cox models. Results: A U-shaped association was observed in the HOMA-IR analysis, with Q3 vs Q1 showing a lower hazard ratio (HR) for any fracture (HR 0.82, 95% CI 0.70-0.97). Similarly, in the TyG index analysis, Q3 vs Q1 was associated with lower risks of any fracture (HR 0.84, 95% CI 0.72-0.98) and major osteoporotic fracture (MOF) (HR 0.80, 95% CI 0.65-0.99). No associations were found for hip or vertebral fractures, and results were unchanged in sensitivity analyses excluding T2DM. Conclusion: Older community-dwelling men in Q3 of HOMA-IR and TyG had modestly lower risks of any clinical fracture and MOF, but associations were inconsistent across quartiles and fracture types. Further studies in other populations are needed to confirm these findings.