WHI observational study: Fracture risk in younger women using the Garvan and FRAX Risk Calculators without DXA-derived BMD
Fracture risk assessment after menopause is generally advised. The study  applied risk assessment by FRAX and Garvan to 63723 women, aged 50-64 years, in the WHI observational study to predict hip fractures and major osteoporotic fractures (MOF) during a 10-year follow-up and to compare it to actual incidental fractures. The specificity of both tools for detecting incident hip fracture was low: Garvan 30.6% (95% confidence interval [CI] 30.3–31.0%) and FRAX 43.1% (95% CI 42.7–43.5%). Both models discriminated poorly between postmenopausal women aged 50–64 years who do and do not experience hip fracture, MOF or clinical fractures during a 10-year follow-up. Specificity was even worse in women of African American and Hispanic ethnicity.
The need for fracture risk assessment at age 50-64 is widely accepted but the method remains controversial. The present study illustrated that FRAX and Garvan without DXA is insufficient. The authors conclude that additional risk factors should be explored. The obvious question is when DXA-derived BMD should be added. All major societies agree that it should be based on risk factors but the threshold for action is ill defined. IMS , NAMS , NOF (US) , and ACOG  regard the presence of two risk factors, in addition to being postmenopausal, as an indication for DXA. IOF recommends that risk be calculated by FRAX (without DXA) but provides no cut-off point.
The United States Preventive Services Task Force (USPSTF)  recommends DXA-screening in women younger than 65, whose fracture risk (based on FRAX®) is equal to or greater than that of a 65-year-old white woman who has no additional risk factors. Based on the U.S. FRAX ® tool, a 65-year-old white woman with no other risk factors has a 9.3% 10-year risk for any osteoporotic fracture. White women between the ages of 50 and 64 years with equivalent or greater 10-year fracture risks based on specific risk factors include but are not limited to the following subtypes: 1) a 50-year-old current smoker with a BMI less than 21 kg/m2, daily alcohol use, and parental fracture history 2) a 55-year-old woman with a parental fracture history 3) a 60-year-old woman with a BMI less than 21 kg/m2 and daily alcohol use; 4) a 60-year-old current smoker with daily alcohol use. Even when DXA is added to FRAX in the younger women, the question remains whether calculated risk is underestimated, especially as FRAX solely uses the femur neck value and does not incorporate spinal osteopenia. There is also the question of whether the fixed threshold probability for pharmacological intervention of a 10-year risk of hip fracture (3%) or MOF (20%) is appropriate in the younger patient. The issue becomes even more complicated when deciding on suitable therapy. Alendronate was shown in the FIT 2 study not to be effective at T-scores > -2.5. For many years menopausal hormone therapy was the only therapy with proven fracture reduction efficacy in osteopenic women. A recent publication has shown the efficacy of zolendronic acid infusion in osteopenic patients, aged 65 years and older, to reduce fractures . In addition to always advocating a bone-friendly lifestyle to all menopausal patients, the presence of risk factors for fracture should be an indication for DXA in women 50-64 years of age. In the osteopenic women MHT can be considered regardless of specific probability thresholds.
Tobie De Villiers
Stellenbosch University, Cape Town, South Africa
- Crandall CJ, Larson J, LaCroix A, Cauley JA, LeBoff MS, Li W, LeBlanc ES, Edwards BJ, Manson JE, Ensrud K. Predicting Fracture Risk in Younger Postmenopausal Women: Comparison of the Garvan and FRAX Risk Calculators in the Women's Health Initiative Study.J Gen Intern Med. 2018 Oct.
- De Villiers TJ, Pines A, Panay N et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric 2013; 16:316–337.
- Shifren J, Gass M. The North American Menopause Society Recommendations for Clinical Care of Midlife Women. Menopause 2015;21:1038-62.
- Cosman F, de Beur S, LeBoff M et al. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int 2014;25:2359-2381.
- ACOG Osteoporosis Guidelines.
- U.S. Preventive Services Task Force: Osteoporosis Screening.
- Reid IR, Horne AM, Mihov B, et al. Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med.