Insulin Resistance Does Not Increase Fracture Risk in Patients Without Diabetes

Although type 2 diabetes is associated with increased fracture risk, there is no association between insulin resistance and fracture risk in older adults without diabetes, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Many previous studies have shown that type 2 diabetes is associated with increased fracture risk. However, the effect of insulin resistance on bone health in patients without diabetes is not clear. The researchers aimed to study the association between insulin resistance, as measured by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), with bone mineral density (BMD) and non-spine fractures in patients without diabetes.

The study sample included 2398 adult patients without diabetes, aged 70 to 79 years at baseline (mean age, 74 ± 3 years; 53% women) who participated in the Health, Aging and Body Composition prospective cohort study. For up to 15 years of follow-up, participants were surveyed every 6 months regarding new fractures that did not result from excessive trauma or pathologic condition. The researchers focused on non-spine fractures and assessed the associations between quartiles of HOMA-IR and BMD and fracture incidence.

Total hip BMD increased with increasing HOMA-IR, and in unadjusted analyses, the mean difference in total hip BMD between the lowest and highest quartiles of insulin resistance was 0.104 g/cm² (P <.001). However, following adjustment for covariates including body mass index (BMI), the association was lost, suggesting body size might have played an important role in this relationship.

Increasing insulin resistance was associated with lower risk for non-spine fracture in unadjusted models (hazard ratio for highest vs lowest quartile of HOMA-IR, 0.65; 95% CI, 0.47-0.89). However, following adjustment for BMI and BMD, this association was lost.

The researchers acknowledged the use of HOMA-IR rather than the hyperinsulinemic euglycemic clamp technique to estimate insulin resistance was an important limitation of this study. In addition, measurements of HOMA-IR, BMI, and BMD were taken only at baseline and may very well have changed during the follow-up.

“In contrast to the relationship between [type 2 diabetes] and fracture risk, we did not find consistent evidence that greater IR [insulin resistance] is associated with increased fracture risk after adjustment for BMI and BMD,” concluded the investigators.

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Reference

Napoli N, Conte C, Pedone C, et al. Effect of insulin resistance on BMD and fracture risk in older adults [published online February 25, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-02539