After the occurrence of the first fracture, osteoporosis is no longer a "silent" disease, and the patient's risk for future fracture is increased several fold. We assessed the location of first osteoporotic fractures among women with osteoporosis. The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a fracture outcomes study of postmenopausal women with osteoporosis. All subjects received supplements containing 500 mg elemental calcium and 400-600 IU vitamin D. We assessed the location of first fractures among women with osteoporosis and no previous fractures at baseline from the placebo group of this trial after 3 years of follow-up. Prespecified fracture sites included vertebral fractures and nonvertebral fractures as defined in the MORE study protocol. Among 875 women (mean age, 64.5 +/- A 7.4 years) with no prevalent vertebral or nonvertebral fractures, 9% experienced their first fracture event during the trial. Fractures of radius and spine each occurred in 3% of patients. Fractures at other individual sites included ankle (0.6%), metatarsal (0.6%), humerus (0.5%), rib (0.5%), patella (0.3%), leg (0.2%), hip (0.2%), and clavicle (0.1%). These data suggest that for postmenopausal women with osteoporosis but no previous fractures, skeletal care should include a focus on preventing spine and radius fractures.