Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

The aim of this prospective study was (1) to identify significant and independent clinical risk factors (CRFs) for major osteoporotic (OP) fracture among peri- and early postmenopausal women, (2) to assess, in this population, the discriminatory capacity of FRAX and bone mineral density (BMD) for the identification of women at high risk of fracture, and (3) to assess whether adding risk factors to either FRAX or BMD would improve discriminatory capacity. The study population included 2651 peri- and early postmenopausal women [mean age (+/- SD): 54 +/- 4 years] with a mean follow-up period of 13.4 years (+/-1.4 years). At baseline, a large set of CRFs was recorded, and vertebral BMD was measured (Lunar, DPX) in all women. Femoral neck BMD also was measured in 1399 women in addition to spine BMD. Women with current or past OP treatment for more than 3 months at baseline (n = 454) were excluded from the analyses. Over the follow-up period, 415 women sustained a first low-energy fracture, including 145 major OP fractures (108 wrist, 44 spine, 20 proximal humerus, and 13 hip). In Cox multivariate regression models, only 3 CRFs were significant predictors of a major OP fracture independent of BMD and age: a personal history of fracture, three or more pregnancies, and current postmenopausal hormone therapy. In the subsample of women who had a hip BMD measurement and who were not receiving OP therapy (including hormone-replacement therapy) at baseline, mean FRAX value was 3.8% (+/-2.4%). The overall discriminative value for fracture, as measured by the area under the Receiver Operating Characteristic (ROC) curve (AUC), was equal to 0.63 [95% confidence interval (CI) 0.56-0.69] and 0.66 (95% CI 0.60-0.73), respectively, for FRAX and hip BMD. Sensitivity of both tools was low (ie, around 50% for 30% of the women classified as the highest risk). Adding parity to the predictive model including FRAX or using a simple risk score based on the best predictive model in our population did not significantly improve the discriminatory capacity over BMD alone. Only a limited number of clinical risk factors were found associated with the risk of major OP fracture in peri- and early postmenopausal women. In this population, the FRAX tool, like other risk scores combining CRFs to either BMD or FRAX, had a poor sensitivity for fracture prediction and did not significantly improve the discriminatory value of hip BMD alone.