Crandall CJ, et al. - The performance of the Fracture Risk Assessment Tool (FRAX) and FRAX-based osteoporosis treatment thresholds under the US National Osteoporosis Foundation (NOF) and UK National Osteoporosis Guideline Group (NOGG) guidelines was assessed among women aged ≥40 years. Registry data were used for all women aged ≥40 years in Manitoba, Canada, with baseline bone mineral density (BMD) testing (n=54,459). According to results, all fracture outcomes at all ages could be forecast by femoral neck T-score and FRAX (with and without BMD). In FRAX-predicted vs observed 10-year major osteoporotic fracture and hip fracture probability, good calibration was noted. Sensitivity for recognizing incident major osteoporotic fracture varied by age, from 0.0% to 26.3% in women 40 to 49 years old and from 49.0% to 93.3% in women aged 80+ years. As continuous measures, the risk gradient for fracture prediction from femoral neck T-score and FRAX (with and without BMD) was strong throughout the age spectrum. Particularly among women aged 40 to 49 years (who have lowest incidence rates), the sensitivity and PPV of the approaches based on dichotomous cut-offs are low. Especially in younger women, threshold-based methods should be reassessed