Successful skeletal aging: a marker of low fracture risk and longevity. The Study of Osteoporotic Fractures (SOF).

Successful aging is multidimensional, and many phenotypes have been proposed. We examined a biomarker of aging based on repeated measures of BMD for up to 15 yr and hypothesized that maintenance of BMD will be associated with low fracture risk and disability and improved survival. We studied 9704 women recruited at four U.S. clinical centers and enrolled in the Study of Osteoporotic Fractures, a longitudinal cohort study. Of these, 8224 women had at least one hip BMD measurement. Hip BMD was measured a maximum of five times over 15 yr. Random effects regression was used to determine a BMD slope for each subject. Three groups were formed-"maintained" BMD: slope >or=0, n = 724 (9%); "expected" BMD loss: slope <0 to <1 SD below mean, n = 6478 (79%); and "accelerated" BMD loss: slope >or=1 SD below mean, n = 1022 (12%). Cox proportional hazards models were used to compare the relative hazard (RH; 95% CI) of fracture, incident mobility disability, and mortality in the maintained and accelerated groups compared with the expected. A 1 SD decrease in the BMD slope was associated with an increased risk of all outcomes. In multivariate models, the RH of nonspine fracture was 0.81 (0.71-0.93) and of hip fracture was 0.36 (0.25-0.53) for women in the maintained compared with the expected group. The incidence of mobility disability was lower in the maintained versus expected group (RH = 0.70; 95% CI = 0.59-0.83), but this was largely explained by other factors. Women who experienced accelerated bone loss were more likely to develop disability (RH = 1.56; 95% CI: 1.33-1.84). Mortality risks were lower in the maintained compared with the expected group (RH = 0.49; 95% CI: 0.42-0.58). In conclusion, a subset of older women maintained their BMD up to 15 yr, suggesting that bone loss is not an inevitable consequence of aging. These women experienced a lower risk of fractures, disability, and mortality, suggesting that this phenotype may be a marker of successful aging.