Discussion
This longitudinal study found that, among postmenopausal women aged 50 to 64 years without osteoporosis on their first BMD test, less than 1% experienced a hip or clinical vertebral fracture and less than 3% experienced a major osteoporotic fracture by 7 years. The analysis accounted for different clinical trajectories (ie, incident osteoporosis, death, or initiation of treatment before a first major osteoporotic fracture was modeled as a competing risk). Our results suggest that younger postmenopausal women without osteoporosis on their first BMD scan are unlikely to benefit from frequent rescreening before age 65 years. Adjustment for several clinical risk factors for fracture did not substantially alter these findings. Women with osteoporosis on their first BMD test (8.5% of the cohort) had a significantly higher risk of fracture before age 65 years than women without osteoporosis.
Empirical data on age-appropriate osteoporosis screening are important because of substantial underutilization of BMD testing in women aged 65 years or older and inappropriate use in other postmenopausal women who do not meet screening criteria in published clinical practice guidelines. In 2011, the National Physicians Alliance initiated a project titled "Promoting Good Stewardship in Clinical Practice" that aimed to develop a list of the top five activities in family medicine, internal medicine, and pediatrics where quality of care could be improved. This list included the recommendation, "don't use DEXA screening for osteoporosis in women under age 65 years or men under 70 years with no risk factors," citing the lack of cost-effectiveness in these groups. Although the project's focus on cost control was understandable, the BMD testing recommendations were not based on original studies testing this hypothesis. Our results substantiate that DXA BMD testing has a lower yield for younger postmenopausal women than for women aged 65 years or older. However, because hip and spine fractures would be catastrophic for working adult women who are otherwise healthy, we do not interpret our results to mean that no postmenopausal women younger than 65 years should have a DXA test. Instead, the data suggest that postmenopausal women would be unlikely to have a major fracture before age 65 years, but development of osteoporosis by BMD criteria remains important because it confers a higher immediate risk of major fracture compared with greater BMD levels. Our results are generalizable to younger postmenopausal women with good general health who are candidates for BMD screening in primary care practice. Our results should not be applied to individuals with existing fragility fractures or secondary causes of osteoporosis who are seen in subspecialty clinics or to individuals who have taken antifracture treatment agents. Those individuals are no longer candidates for screening because they have higher baseline risk for subsequent fractures and thereby different testing and treatment criteria.
Current clinical practice guidelines encourage the use of risk factors for fracture to select postmenopausal women younger than 65 years who are good candidates for DXA testing. Two analyses of large cohorts of postmenopausal women aged 50 to 64 years at baseline suggest that simple fracture risk assessment tools (including one calculated from age and weight) perform as well as more complicated tools for this purpose. Our data can help inform a BMD testing interval for postmenopausal women who are screened before age 65 years. Using the more conservative time estimates for major osteoporotic fracture, clinicians might allow women aged 50 and 54 years without osteoporosis on their first BMD test to wait 10 years for their next test. Similarly, women aged 60 to 64 years without osteoporosis on their first BMD test might wait until after age 65 years for their next test. Other approaches have been considered. For example, Reid and Gamble's modeling study based on doubling time for predicted hip fracture risk suggested that a BMD screening interval of 5 to 6 years may be appropriate for many intermediate-risk women aged 65 years or older. This 5- to-6-year interval might be interpreted as a conservative estimate for intermediate-risk younger postmenopausal women.
Women found to have osteoporosis in this age range are no longer candidates for a routine screening schedule. We included these women in the analysis because if they had osteoporosis but did not sustain a fracture until well after age 65 years, the value of any BMD screening before age 65 years would be questioned. Instead, we found that all (3 of 3) of the women aged 50 to 54 years and more than half (16 of 28) of women aged 55 to 64 years with baseline osteoporosis who had a major osteoporotic fracture during follow-up had the fracture before age 65 years. This suggests that clinicians should promptly counsel younger postmenopausal women with osteoporosis regarding the benefits and harms of treatment, rather than assuming that this discussion can be deferred. Although women with osteoporosis had a substantially higher risk of fracture, most of the hip and clinical vertebral fractures in the cohort as a whole occurred in women with baseline T scores higher than −2.50 (ie, 65 of 3,724 [1.7%] women with baseline T scores > −2.50 vs 25 of 344 [7.3%] women with baseline T scores ≤ −2.50 had a hip or clinical vertebral fracture). These results are consistent with other longitudinal studies of postmenopausal women and demonstrate that BMD testing cannot identify every individual who will have a future fragility fracture. Such findings emphasize the importance of further investigations of risk factor assessment and screening methods to identify poor bone quality that also contributes to increased fracture risk.
According to current clinical practice guidelines, women with asymptomatic radiographic vertebral fractures should also receive osteoporosis treatment regardless of BMD T-score level. Radiographic vertebral fracture data were not available in the WHI study, but a US population—based study reported very low vertebral fracture incidence rates for this age range of women (215-349 per 100,000 [0.35%] women aged 50-64 y). Considering that one third or fewer of incident radiographically identified vertebral fractures are clinically diagnosed, clinicians may consider additional imaging (lateral thoracic and lumbar spine radiographs or densitometric vertebral fracture assessment imaging) in postmenopausal women with BMD T scores between −1.5 and −2.4 who demonstrate height loss or other risk factors that may suggest prevalent radiographic vertebral fracture.
The low incidence rates of hip or clinical vertebral fractures in our analysis are consistent with the 2008 Cochrane review of alendronate treatment, which showed very low absolute risk reductions (ARRs) for hip and clinical vertebral fractures in younger postmenopausal women. Women aged 50 to 54 years who were treated with alendronate had 5-year ARRs of 0.1% for first spine fracture and 0.0% for first hip fracture, with analogous figures of 0.5% and 0.1% for women aged 60 to 64 years and 0.7% and 0.4% for women aged 65 to 69 years. In contrast, the ARR for alendronate-treated women aged 90 years or older was 11.1% for spine fracture and 2.1% for hip fracture. The very low treatment efficacy of alendronate in younger women was probably attributable to their low baseline (untreated) fracture rates, such that treatments did not confer a significant absolute fracture risk reduction. Because of these low fracture rates, BMD screening and treatment in younger postmenopausal women are likely to have less of an impact on the population burden of fracture compared with screening and treatment in women aged 65 years or older. Careful selection of women for screening and treatment is especially important before age 65 years because the risk of complications, such as atypical femoral fractures and osteonecrosis of the jaw, seems to rise with increasing duration of exposure to bisphosphonates. The 3% fracture threshold used in our analysis of major osteoporotic fractures was much lower than the 20% estimated fracture risk threshold for which treatment may be recommended according to the World Health Organization FRAX fracture risk algorithm. Thus, our time estimates for the major osteoporotic fracture endpoint should not be viewed as an estimated time until treatment initiation.
Our study had several limitations. Our time estimates were based only on transitions to major fracture; the full benefits and risks of screening and cost-effectiveness were not considered. The analysis had inadequate power to study fracture risk in subgroups defined by individual risk factors. For example, a higher proportion of women with osteoporosis and current hormone therapy use at baseline had a hip or clinical vertebral fracture during follow-up compared to women with osteoporosis and without current hormone therapy use at baseline. This might have represented confounding by treatment indication or mere variability in an estimate based on very few fracture events. More than 97% of the original WHI participants were not eligible for this analysis because they were not part of the BMD cohort. However, our study population included 89.9% (4,068 of 4,527) of the WHI participants with technically adequate BMD measurements at one or more study examinations. Seventy-four percent of our sample comprised white women, and 15% comprised black women; because the prevalence of hip osteoporosis in white women is lower than the prevalence of hip osteoporosis in African-American women by National Health and Nutrition Examination Survey estimates, our calculated estimates of time to major fracture are likely to be reasonable estimates for women of all races. Because of rare fracture events in lowest-risk women, some of our time estimates were extrapolations with wide CIs. Strengths of the analysis include the large size of the cohort and the long follow-up period involving repeated BMD testing, fracture ascertainment between study visits, inclusion of the lumbar spine in BMD measurements, and inclusion of mortality as a competing risk.