Low serum concentrations of alpha-tocopherol are associated with increased risk of hip fracture. A NOREPOS study

We investigated the risk of hip fracture according to circulating alpha-tocopherol, a plant-derived substance with antioxidant properties, in community-dwelling older Norwegians. We found a linear increasing risk of hip fracture with lower serum alpha-tocopherol concentrations, with a 51 % higher risk in the lowest compared to the highest quartile. Oxidative stress is a suggested contributing cause of osteoporosis and fractures. Vitamin E (alpha-tocopherol) has potent antioxidant properties in humans. The relationship between circulating alpha-tocopherol and fracture risk is not established. The aim of this study was to investigate the association between serum alpha-tocopherol concentrations and risk of hip fracture during up to 11 years of follow-up. We performed a case-cohort analysis among 21,774 men and women aged 65-79 years who participated in four community-based health studies in Norway 1994-2001. Serum alpha-tocopherol concentrations at baseline were determined in 1,168 men and women who subsequently suffered hip fractures (median follow-up 8.2 years) and in a random sample (n = 1,434) from the same cohort. Cox proportional hazard regression adapted for gender-stratified case-cohort data was performed. Median (25, 75 percentile) serum alpha-tocopherol was 30.0 (22.6, 38.3) mu mol/L, and it showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11 (95 % confidence interval (CI) 1.04-1.20) per 10-mu mol/L decrease in serum alpha-tocopherol, adjusted for gender and study center. The lowest compared to the highest quartile conferred an HR of 1.51 (95 % CI 1.17-1.95), adjusted for gender and study center. Adjustment for smoking, month of blood sample, BMI, education, physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D) yielded similar results. Taking serum total cholesterol concentration into account attenuated the association somewhat: HR of hip fracture was 1.37 (95 % CI 1.05-1.77) in first versus fourth quartile of serum alpha-tocopherol/total cholesterol ratio. Low serum concentrations of alpha-tocopherol were associated with increased risk of hip fracture in older Norwegians.