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_2α (a major F₂-isoprostane and a biomarker of oxidative stress) and a control, 15-keto-dihydro-PGF_2α (a biomarker of inflammatory response), were measured in urinary samples and their association with BMD and quantitative ultrasound (QUS) measurements were examined. In multivariate linear regression analyses, 8-iso-PGF_2α levels were negatively associated with both BMD and QUS. In contrast, no association was found for 15-keto-dihydro-PGF_2α. 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.