Several epidemiological studies have identified clinical factors that predict the risk of hip fractures in elderly women independently of the level of bone mineral density (BMD), such as low body weight, history of fractures, and clinical risk factors for falls. Their relevance in predicting all fragility fractures in all postmenopausal women, including younger ones, is unknown. The objective of this study was to identify independent predictors of all osteoporosis-related fractures in healthy postmenopausal women. We prospectively followed for 5.3 +/- 1.1 years a cohort of 672 healthy postmenopausal women (mean age 59.1 +/- 9.8 years). Information on social and professional conditions, demographic data, current and past medical history, fracture history, medication use, alcohol consumption, caffeine consumption, daily calcium intake, cigarette smoking, family history of fracture, and past and recent physical activity was obtained. Anthropometric and total hip bone mineral density measurements were made. Incident falls and fractures were ascertained every year. We observed 81 osteoporotic fractures (annual incidence, 21 per 1000 women/year). The final model consisted of seven independent predictors of incident osteoporotic fractures: age > or = 65 years, odds ratio estimate (OR), 1.90 [95% confidence interval (CI) 1.04-3.46], past falls, OR, 1.76 (CI 1.00-3.09), total hip bone mineral density (BMD) < or = 0.736 g/cm(2), OR, 3.15 (CI 1.75-5.66), left grip strength < or = 0.60 bar, OR, 2.05 (CI 1.15-3.64), maternal history of fracture, OR, 1.77 (CI 1.01-3.09), low physical activity, OR, 2.08 (CI 1.17-3.69), and personal history of fragility fracture, OR, 3.33 (CI 1.75-5.66). In contrast, body weight, weight loss, height loss, smoking, neuromuscular coordination assessed by three tests, and hormone replacement therapy were not independent predictors of all fragility fractures after adjustment for all variables. We found that some--but not all--previously reported clinical risk factors for skeletal fragility predicted all fragility fractures independently of BMD in healthy postmenopausal women, although they differed somewhat from those predicting specifically hip fractures in elderly women. These risk factors appear to reflect quality of bone structure (previous fragility fracture), lifestyle habits (physical activity), muscle function and health status (grip strength), heredity (maternal history of fracture), falls, and aging. Measurements of these variables should be included in the clinical assessment of the risk of osteoporotic fractures in postmenopausal women.