Studies of the association between the presence of osteoarthritis (OA) and the risk of osteoporotic fractures have produced conflicting results. To address this question further, we have examined the association between self-reported, validated fractures and radiological OA at multiple sites in a large population of normal Caucasian women aged 45-65 yr. Despite having increased bone mineral density (BMD) of 5.3%, subjects with hip OA had a significantly increased risk of fracture [odds ratio (OR) 2.38, 95% CI 1.06-5.35] compared to controls. Subjects with lumbar spine OA, however, had a significantly reduced risk of fracture (OR 0.45, 95% CI 0.23-0.80) compared to controls. This association was not explained by differences in BMD, weight, sex hormones or physical activity. No clear association was seen with fracture for hand or knee OA. These data suggest that the increased risk of fracture in subjects with OA of the hip is most likely to be due to mechanical and locomotor factors, such as the risk of falling.