ABSTRACT: BACKGROUND: Oxidative stress (OxS) has recently been linked with osteoporosis; however, we do not know the influence of OxS as an independent risk factor for this disease. METHODS: We conducted a case-control study in 94 subjects > or =60 years of age, 50 healthy and 44 with osteoporosis. We measured total antioxidant status, plasma lipid peroxides, antioxidant activity of superoxide dismutase and glutathione peroxidase (GPx), and calculated the SOD/GPx ratio. Bone mineral density was obtained at the peripheral DXA in calcaneus using a portable Norland Apollo Densitometer. Osteoporosis was considered when subjects had a BMD of 2.5 standard deviations or more below the mean value for young adults. RESULTS: GPx antioxidant activity was significantly lower in the group of subjects with osteoporosis in comparison with the group of healthy subjects (p < 0.01); in addition, the SOD/GPx ratio was significantly higher in the group of individuals with osteoporosis (p < 0.05). In logistic regression analysis, we found OxS to be an independent risk factor for osteoporosis (odds ratio [OR] = 2.79; 95% confidence interval [95% CI] = 1.08-7.23; p = 0.034). CONCLUSION: Our findings suggest that OxS is an independent risk factor for osteoporosis linked to increase of SOD/GPx ratio.