Outcomes of FRAX-Predicted Risk Treatment Thresholds in Women

Predicting the risk for hip fracture or major osteoporotic fracture based on the Fracture Risk Assessment Tool (FRAX) or femoral neck bone mineral density (BMD) T-score is better in older women compared with women age 40 to 49. According to study results published in Journal of Bone and Mineral Research, both femoral BMD T-score threshold ≤-2.5 and FRAX-based osteoporosis treatment thresholds have low sensitivity for fracture in younger women.

According to the investigators, the FRAX is based on clinical risk factors and can predict the 10-year absolute risk for hip or major osteoporotic fracture (humerus, hip, clinical vertebral, forearm). Prospective cohort studies have shown FRAX can predict occurrence of fracture in adult women and men.

The United Kingdom National Osteoporosis Guideline Group (NOGG) recommends the use of FRAX alone in treatment decisions in patients without prior fracture and with an age-dependent treatment threshold. The National Osteoporosis Foundation (NOF) recommends the use of FRAX with BMD only in postmenopausal women with osteopenia, with the treatment threshold set at 10-year hip fracture risk of ≥3% and/or major osteoporotic fracture risk of ≥20%.

In this large registry-based cohort of women aged ≥40 from Manitoba, Canada, the researchers examined the outcomes in 54,459 participants (mean age, 63.9 years) who had undergone BMD measurement and completed at least 5 years of follow-up. They collected data from health services regarding incidence of hip fracture, major osteoporotic fracture, and clinical fracture during the follow-up period (mean follow-up, 10.5 years).

FRAX-predicted risk threshold was defined as 10-year risk for major osteoporotic fracture ≥20% or 10-year risk for hip fracture ≥3% (NOF threshold) or age-dependent risk (NOGG threshold). Women were stratified into decades of age based on age at BMD testing.

Incidence of major osteoporotic fracture during follow-up was 11.4%, with a fracture incidence of 3.5% for hip fracture and 14.9% for any clinical fragility fracture. The incidence of hip, major osteoporotic, and any clinical fragility fracture increased with increased age at baseline.

For every 1 standard deviation (SD) higher FRAX score there was a 1.5- to 4.7-fold increased fracture risk and for every 1 SD lower femoral neck BMD there was a 1.6- to 3.0-fold increased fracture risk.

The sensitivity of femoral neck BMD T-score ≤-2.5, FRAX-predicted major osteoporotic fracture ≥20% (NOF threshold) or FRAX risk above age-dependent cutoff (NOGG threshold) was higher for prediction of hip fracture (BMD T-score ≤-2.5: 38.1%; NOF threshold: 62.2%; NOGG threshold: 59.0%) than for prediction of major osteoporotic fracture (25.7%, 20.3%, and 27.3%, respectively).

All 3 strategies had age-dependent sensitivity, with much lower sensitivity for women aged 40 to 49 compared with older women. The incidence of major osteoporotic fracture was between 0.0% and 26.3% in women aged 40 to 49 compared with incidence between 49.0% and 93.3% in women aged 80 and older.

The study had a few limitations, including a nonrandomized design and indirect assessment of fracture based on administrative databases without reviewing the imaging studies.

According to the researchers, “previous prospective studies have not performed similar direct comparisons of the performance and potential implications of threshold-based and osteoporosis treatment algorithms.” They believe these results will help to inform future guidelines for the management of osteoporosis.

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Reference

Crandall CJ, Schousboe JT, Morin SN, Lix LM, Leslie W. Performance of FRAX and FRAX-based treatment thresholds in women aged 40 and older: the Manitoba BMD registry [published online March 28, 2019]. J Bone Miner Res. doi:10.1002/jbmr.3717