Osteoporosis and its consequent increase in fracture risk is a major health concern for postmenopausal women and older men and has the potential to reach epidemic proportions. The "gold standard" for osteoporosis diagnosis is bone densitometry. However, economic issues or availability of the technology may prevent the possibility of mass screening. The goal of this study was to develop and validate a clinical scoring index designed as a prescreening tool to help clinicians identify which women are at increased risk of osteoporosis [bone mineral density (BMD) T-score -2.5 or less] and should therefore undergo further testing with bone densitometry. Records were analyzed for 1522 postmenopausal females over 50 years of age who had undergone testing with dual-energy X-ray absorptiometry (DXA). Osteoporosis risk index scores were compared to bone density T-scores. Hologic QDR 4500 technology was used to measure BMD at the femoral neck and lumbar spine (L1-L4). Participants who had a previous diagnosis of osteoporosis or were taking bone-active medication were excluded. Receiver-operating characteristic (ROC) analysis was used to identify the specific cutpoint value that would identify women at increased risk of low BMD. A simple algorithm based on age, weight, history of previous low impact fracture, early menopause, and corticosteroid therapy was developed. Validation of this five-item osteoporosis prescreening risk assessment (OPERA) index showed that the tool, at the recommended threshold (or cutoff value) of two, had a sensitivity that ranged from 88.1 [95% confidence interval (CI) for the mean: 86.2-91.9%] at the femoral neck to 90% (95% CI for the mean: 86.1-93.1%) at the lumbar spine area. Corresponding specificity values were 60.6 (95% CI for the mean: 57.9-63.3%) and 64.2% (95% CI for the mean: 61.4-66.9%), respectively. The positive predictive value (PPV) ranged from 29 at the femoral neck to 39.2% at the lumbar spine, while the corresponding negative predictive values (NPVs) reached 96.5 and 96.2%, respectively. Based on this cutoff value, the area under the ROC curve was 0.866 (95% CI for the mean: 0.847-0.882) for the lumbar spine and 0.814 (95% CI for the mean: 0.793-0.833) for the femoral neck. We conclude that the OPERA is a free and effective method for identifying Italian postmenopausal women at increased risk of osteoporosis. Its use could facilitate the appropriate and more cost-effective use of bone densitometry in developing countries.