Muscle mass assessed by the D3-creatine dilution method and incident self-reported disability and mortality in a prospective observational study of community-dwelling older men

Peggy M. Cawthon, Terri Blackwell, Steven R. Cummings, Eric S. Orwoll, Kate A. Duchowny, Deborah M. Kado, Katie L. Stone, Kristine E. Ensrud, Jane A. Cauley, William J. Evans

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5 Scopus citations


Background: Whether low muscle mass is a risk factor for disability and mortality is unclear. Associations between approximations of muscle mass (including lean mass from dual-energy x-ray absorptiometry [DXA]), and these outcomes are inconsistent. Methods: Muscle mass measured by deuterated creatine (D3Cr) dilution and appendicular lean mass (ALM, by DXA) were assessed at the Year 14 Visit (2014–2016) of the prospective Osteoporotic Fractures in Men study (N = 1,425, age 77–101 years). Disability in activities of daily living (ADLs), instrumental ADLs, and mobility tasks was self-reported at the Year 14 visit and 2.2 years later; deaths were centrally adjudicated over 3.3 years. Relative risks and 95% confidence intervals (CI) were estimated per standard deviation decrement with negative binomial, logistic regression, or proportional hazards models. Results: In age- and clinical center-adjusted models, the relative risks per decrement in D3Cr muscle mass/wgt was 1.9 (95% CI: 1.2, 3.1) for incident self-reported ADL disability; 1.5 (95% CI: 1.3, 1.9) for instrumental ADL disability; and 1.8 (95% CI: 1.5, 2.2) for mobility disability. In age-, clinical center-, and weight-adjusted models, the relative risks per decrement in D3Cr muscle mass was 1.8 (95% CI: 1.5, 2.2) for all-cause mortality. In contrast, lower DXA ALM was not associated with any outcome. Associations of D3Cr muscle mass with these outcomes were slightly attenuated after adjustment for confounding factors and the potentially mediating effects of strength and physical performance. Conclusions: Low muscle mass as measured by D3Cr dilution is a novel risk factor for clinically meaningful outcomes in older men.

Original languageEnglish (US)
Pages (from-to)123-130
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number1
StatePublished - 2020

Bibliographical note

Funding Information:
Dr. Cawthon is a consultant to BioAge Labs and has grants from Abbott and Nestle to her institution, all for work unrelated to this paper. Although Dr. Evans is listed as an inventor on the issued patents, he derives no income from this intellectual property. Dr. Stone and Ms. Blackwell receive salary support through a grant from Merck, Inc. to their institution for work unrelated to this paper. All other authors report nothing to disclose.

Funding Information:
The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. Funding for the D3Cr muscle mass measure was provided by NIAMS (grant number R01 AR065268). GlaxoSmithKline provided in-kind support by providing the d3-creatine dose and analysis of urine samples.

Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.


  • Death
  • Disability
  • Muscle mass


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