Association between global biomarkers of oxidative stress and hip fracture in postmenopausal women: a prospective study.

Human studies suggest that oxidative stress is a risk factor for osteoporosis, but its relationship with fracture risk is poorly understood. The purpose of the present study was to investigate the association between biomarkers of oxidative stress and hip fracture in postmenopausal women. We conducted a prospective study in the Nurses' Health Study among 996 women aged 60 years or older at baseline blood collection in 1989-1990. Plasma fluorescent oxidation products (FlOPs) were measured at three excitation/emission wavelengths (360/420 nm named as FlOP_360; 320/420 nm named as FlOP_320; and 400/475 nm named as FlOP_400). FlOPs are generated from many different pathways (lipid, protein, and DNA) and reflect a global oxidation burden. FlOP assay is 10-100 times more sensitive than measurement of malondialdehyde. We used Cox proportional hazards regression model to investigate the association between baseline plasma FlOPs and the risk of hip fracture, adjusting for multiple hip fracture risk factors such as age, history of osteoporosis, history of hypertension, prior fracture, and smoking status. Forty-four hip fractures (4.4%) were identified during the follow-up (maximum = 23 years). In the multivariable model, the hazard ratios (HRs) of hip fracture in the second and third tertiles of FlOP_320 were 2.11 (95% confidence interval [CI] = 0.88-5.10) and 2.67 (95% CI = 1.14-6.27), respectively, in comparison with the lowest tertile, and the risk increased linearly with increasing FlOP_320 (p for trend = 0.021). Neither FlOP_360 nor FlOP_400 was significantly associated with risk of hip fracture (tertile 3 versus tertile 1: HR = 0.70, 95% CI = 0.32-1.54, p for trend = 0.386 for FlOP_360; and HR = 0.88, 95% CI = 0.40-1.96, p for trend = 0.900 for FlOP_400). In this prospective study, higher plasma FlOP_320 was an independent risk factor for hip fracture. Our results need further confirmation.