Effect of Insulin Resistance on BMD and Fracture Risk in Older Adults

Abstract Context Adults with type 2 diabetes (T2D) have higher fracture risk compared with nondiabetics, despite having higher bone mineral density (BMD). Insulin resistance (IR) has been associated with increased BMD. It is not known if IR increases fracture risk. Objective We investigated the relationship among IR HOMA-IR, BMD, and incident nonspine fractures in nondiabetic individuals. Design Participants included 2398 community-dwelling, nondiabetic older adults (age 74 ± 3 years, 53% women, 38% black) in the Health, Aging and Body Composition Prospective Cohort Study [median follow-up: 12 (interquartile range: 6) years]. Results The cut-off values for the HOMA-IR quartiles were 1.05, 1.54, and 2.33. Total hip BMD was 0.104 g/cm2 higher in the fourth vs the first HOMA-IR quartile (P < 0.001). This difference was attenuated after adjustment for BMI (adjusted mean difference 0.007 g/cm2; P = 0.371). In unadjusted models, fracture risk was lower in those with higher HOMA-IR [hazard ratio (HR) 0.86 (95% CI 0.73 to 1.01) and 0.65 (95% CI 0.47 to 0.89) for the third and fourth quartile, respectively, vs the first quartile]. However, after adjustment for BMD and BMI, fracture risk was significantly higher in the third quartile (HR 1.19, 95% CI 1.00 to 1.41) and tended to be increased in the fourth quartile (HR 1.12, 95% CI 0.87 to 1.46) vs the first quartile. Conclusions Greater IR is associated with higher BMD in nondiabetic older adults. In contrast to the relationship between T2D and fracture risk, we did not find consistent evidence that greater IR is associated with increased fracture risk after adjustment for BMI and BMD. We found lower risk of fracture with higher insulin resistance in older adults without diabetes. This inverse association was lost after adjustment for BMI and BMD.