F2-Isoprostanes Are Associated With Increased Fracture Risk in Type 2 Diabetes

Context: Fracture risk is higher in type 2 diabetes (T2D) for a given bone mineral density (BMD) level. Increased oxidative stress in T2D induces diabetic complications and may affect T2D bone fragility.

Objective: To investigate whether the levels of plasma F2-isoprostanes, a reliable oxidative stress marker, are associated with incident clinical fracture risk in older adults with diabetes.

Design and setting: An observational cohort study was conducted in a well-characterized cohort from Health, Aging, and Body Composition study.

Participants: Older black and white ambulatory adults with baseline plasma F2-isoprostanes measurements (baseline age 70-79 years, T2D: N=132; non-diabetes: N=571) were selected from the study cohort of 3075 individuals.

Main outcome measures: Incident clinical fractures.

Results: In the Cox proportional hazard model with multivariate adjustments (including BMD, medications, and other risk factors), a 93% increase in incident clinical fracture risk was significantly associated with each SD increase in log plasma F2-isoprostanes in the T2D group (HR: 1.93, 95% CI 1.26-2.95, p=0.002), but there was no evidence of an association in the non-diabetes group (HR: 0.98, 95% CI 0.81-1.18, p=0.79, p for interaction < 0.001). Log plasma F2-isoprostanes were moderately correlated with a decline in baseline total hip BMD (r=-0.25, p=0.003), and with a 4-year decrease in total hip BMD (r=-0.28, p=0.008) in T2D. There was no evidence of correlation between log plasma F2-isoprostanes and circulating glycoxidation markers or bone turnover markers in either group.

Conclusions: Plasma F2-isoprostanes levels in individuals with diabetes are associated with increased incident clinical fracture risk independently of baseline BMD.