Predictive value of DXA appendicular lean mass for incident fractures, falls and mortality, independent of prior falls, FRAX and BMD: Findings from the Women's Health Initiative (WHI).

In the Women's Health Initiative (WHI), we investigated associations between baseline DXA appendicular lean mass (ALM) and risk of incident fractures, falls and mortality (separately for each outcome) amongst older postmenopausal women, accounting for bone mineral density (BMD), prior falls and 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 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%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 7-15% 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 (MrOS 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. This article is protected by copyright. All rights reserved.