Abstract
ABSTRACTIn the Women's Health Initiative (WHI), we investigated associations between baseline dual‐energy X‐ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height2) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height2 (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow‐up time, and randomization group), greater ALM/height2 was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T‐score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height2 and incident falls. However, there was a 7% to 15% increase in risk of death during follow‐up for each SD greater ALM/height2, depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA‐ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T‐score. However, intriguing positive, but modest, associations between ALM/height2 and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Highlights
Adjustment for FRAX probability of major osteoporotic fracture calculated with or without femoral neck bone mineral density (BMD) attenuated the associations to close to unity except for hip fracture (GR = 0.88 [95% confidence intervals (CI) 0.78–1.00] and gradient of risk (GR) = 0.86 [95% CI 0.76–0.98]) for FRAX with and without BMD, respectively)
For each standard deviation greater appendicular lean mass (ALM)/height2, the risk of death during follow-up was 13% higher (GR = 1.13 [95% CI 1.08–1.18]; Table 3). This was not materially changed by adjustment for either prior falls, FRAX, or femoral neck BMD. We investigated whether this positive association between ALM/height2 and death might be explained by Dual-energy X-ray absorptiometry (DXA) total fat mass or measured waist/hip ratio, but additional adjustment for these variables did not materially alter the relationship; waist/hip ratio GR = 1.07 [95% CI 1.02–1,12])
Consistent with our findings in older men, we have demonstrated that greater DXA ALM/height2 is modestly predictive of lower risk of incident fractures but that this association is markedly attenuated by adjustment for femoral neck BMD
Summary
Dual-energy X-ray absorptiometry (DXA)–derived appendicular lean mass (ALM) is central to the more than 10 current operational definitions of sarcopenia.[1,2] Concerns over the predictive value of DXA ALM for incident health outcomes such as fractures, falls, and death have led to more recent sarcopenia definitions incorporating measures of physical performance/function and muscle strength, rather than being based solely on ALM.[1,2] the most recent European working group consensus definition focuses principally on physical function as the initial criterion for sarcopenia definition[3] and the 2020 US Sarcopenia Definitions and Outcomes Consortium approach dispenses with ALM entirely.[4,5] There is evidence that DXA ALM is variably predictive of fracture outcomes in men, when femoral neck bone mineral density (BMD) is included in the analyses.[1]. Given that the acquisition of DXA ALM requires an additional scan, which may take between 5 and 15 minutes depending on the instrument and the size of the participant, if it does not add useful risk information for a particular outcome over and above more obtainable measures, such as femoral neck BMD (for which the scanning time is usually less than 30 seconds), FRAX probability, or history of falls, its value as part of sarcopenia definitions is questionable, at least in the context of that outcome.[1] Building on our previous findings in men, the aim of the present study was to examine, in a large population of older women, first whether DXA ALM is predictive of incident fractures independent of current measures such as femoral neck BMD, prior falls, and FRAX probability, and second to elucidate associations between baseline DXA ALM and incident falls and mortality
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