Free radicals have been shown to be involved in bone resorption in vitro and in rodents. We studied the effect of oxidative stress on bone mineral density (BMD) in 48 women and 53 men from a population-based study. The levels of 8-iso-PGF(2 alpha) (a major F-2-isoprostane and a biomarker of oxidative stress) and a control, 15-keto-dihydro-PGF(2 alpha) (a biomarker of inflammatory response), were measured in urinary samples and their association with BAM and quantitative ultrasound (QUS) measurements were examined. In multivariate linear regression analyses, 8-iso-PGF(2 alpha) levels were negatively associated with both BNM and QUS. In contrast, no association was found for 15-keto-dihydro-PGF(2 alpha). Our findings establish a biochemical link between increased oxidative stress and reduced bone density and provide a rational for further studies investigating the role of pro- and antioxidants in osteoporosis.