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

Abstract

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 (AE SD): 54 AE 4 years] with a mean follow-up period of 13.4 years (AE1.4 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 ¼ 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% (AE2.4%). 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. ß

Potential role of FRAX analysis in postmenopausal women with osteopenia

“…However, only 68 patients, during this follow up period, were hospitalized at the Institute for Prevention, Treatment and Rehabilitation of Rheumatic and Cardiovascular Diseases "Niška Banja", which may explain the high incidence of the corticosteroids administration, and rheumatoid arthritis presence, in the subject's group, as a risk factors for the fractures. Previous fracture as the most common risk factor for the fracture development, obseved in our study, is in agreement with previous reports [11,12]. Namely, these studies, which prospectively followed up 2631 women with early menopause or in perimenopause, in addition of the fracture in the personal anamnesis, demostrated that the number of pregnancies, as well as the intake of hormonal substitution in the early perimenopause, represents a significant risk factor for the future fractures.…”

“…The presented results showed that the previous fracture was present in 108 (28,05%) women, indicating that patients were relatively late sent to DXA examination. Late DXA diagnostics is in line with long duration of menopause (10.36 ± 6.7) in subjects, before BMD evaluation, while other studies were conducted in women with early menopause or in perimenopause [11,12]. Analysis of DXA results, in patients where only L spine BMD was evaluated, demonstrated that osteopenia, but not osteoporosis, was the most common DXA finding, indicating that hip BMD evaluation may significantly improve sensitivity of the DXA analysis.…”

Absolute fracture risk assessment using lumbar spine and femoral neck bone density measurements: Derivation and validation of a hybrid system

“…(5) Attempts to confirm this in additional cohorts have met with mixed results. Tré mollieres and colleagues (29) did not demonstrate value in using FRAX over BMD alone, but a recent report from Manitoba did find that FRAX with BMD provided better stratification for major osteoporotic and hip fractures than BMD or FRAX clinical risk factors alone. (21) Limitations to this analysis are acknowledged.…”

Increasing body fat mass reverses bone loss in osteopenia as detected by dual-energy X-ray absorptiometry scans

“…Many tools exist to help estimate the risk of future fragility fractures so that preventative treatment can be appropriately targeted (3,4). However, while these tools are often very specific, there is doubt regarding their sensitivity compared with BMD measurement alone (5,6). To accurately predict the future risk of fracture, we need to understand better the factors that affect the change in BMD.…”