Global biomarkers of oxidative stress and fractures: a matched case-control study

Background: Evidence for a relationship between oxidative stress and osteoporotic fractures in humans is limited. Fluorescent oxidation products (FlOPs, excitation/emission wavelengths 320/420nm denoted FlOP_320; 360/420nm [FlOP_360]; and 400/475nm [FlOP_400]) are global biomarkers of oxidative stress, and reflect oxidative damage to proteins, phospholipids, and nucleic acids. We investigated the association between FlOPs and a recent osteoporotic fracture.

Methods: We conducted a case-control study in a Chinese population aged 50 years or older. A recent osteoporotic fracture in the cases was confirmed by x-ray. Cases were matched with community-based non-fracture controls (1:2 ratio) for age (± 4 years) and sex. In addition, we conducted a sensitivity unmatched case-control study which included all fracture cases and all eligible non-fracture controls prior to matching. Plasma FlOPs were measured with a fluorescent microplate reader. We used unconditional logistic regression to analyze the association between FlOPs (per 1-SD increase in logarithmic scale) and fracture; odds ratios (OR) and 95% confidence intervals (95% CI) were reported.

Results: Forty-four cases and 88 matched controls (mean age: 68.2 years) were included. After covariate adjustment (i.e., body mass index, physical activity, and smoking), higher FlOP_360 (OR = 1.85; 95% CI = 1.03 – 3.34) and FlOP_400 (OR = 13.29; 95% CI = 3.48 – 50.69) levels, but not FlOP_320 (OR = 0.56; 95% CI = 0.27 – 1.15), were associated with increased fracture risk. Subgroup analyses by fracture site and unmatched case-control study found comparable associations of FlOP_360 and FlOP_400 with hip and non-hip fractures.

Conclusions: Higher FlOP_360 and FlOP_400 levels were associated with increased risk of fracture, and this association was comparable for hip and non-hip fractures. Prospective studies are warranted to confirm this finding.