A protocol for remote collection of skeletal muscle mass via D3-creatine dilution in community-dwelling postmenopausal women from the Women's Health Initiative

Background There is emerging evidence that cancer and its treatments may accelerate the normal aging process, increasing the magnitude and rate of decline in functional capacity. This accelerated aging process is hypothesized to hasten the occurrence of common adverse agerelated outcomes in cancer survivors, including loss of muscle mass and decrease in physical function. However, there is no data describing age-related loss of muscle mass and its relation to physical function in the long-term in cancer survivors. Methods This study protocol describes the use of a novel method of muscle mass measurement, D3- creatine dilution method (D3Cr), in a large sample (n∼6000) of community dwelling postmenopausal women from the Women's Health Initiative (WHI). D3Cr will be used to obtain a direct measure of muscle mass remotely. Participants will be drawn from two sub-cohorts embedded within the WHI that have recently completed an in-home visit. Cancer survivors will be drawn from the Life and Longevity After Cancer (LILAC) cohort, and cancer-free controls will be drawn from the WHI Long Life Study 2. The overall objective of this study is to examine the antecedents and consequences of low muscle mass in cancer survivors. The study aims are to: 1) create age-standardized muscle mass percentile curves and z-scores to characterize the distribution of D3- muscle mass in cancer survivors and non-cancer controls, 2) compare muscle mass, physical function, and functional decline in cancer survivors and non- cancer controls, and 3) use machine learning approaches to generate multivariate risk-prediction algorithms to detect low muscle mass. Discussion The D3Cr method will transform our ability to measure muscle mass in large-scale epidemiologic research. This study is an opportunity to advance our understanding of a key source of morbidity among older and long-term female cancer survivors. This project will fill knowledge gaps, including the antecedents and consequences of low muscle mass, and use innovative methods to overcome common sources of bias in cancer research. The results of this study will be used to develop interventions to mitigate the harmful effects of low muscle mass in older adults and promote healthy survivorship in cancer survivors in the old (>65) and oldest-old (>85) age groups.