Association Between Muscle Mass Determined by D3-Creatine Dilution and Incident Fractures in a Prospective Cohort Study of Older Men

The Osteoporotic Fractures in Men (MrOS) Study Research Group

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17 Scopus citations


The relation between a novel measure of total skeletal muscle mass (assessed by D3-creatine dilution [D3Cr]) and incident fracture is unknown. In 1363 men (mean age 84.2 years), we determined D3Cr muscle mass; Fracture Risk Assessment Tool (FRAX) 10-year probability of hip and major osteoporotic (hip, humerus, vertebral, forearm) fracture; and femoral neck bone mineral density (BMD) (by dual-energy X-ray absorptiometry [DXA]). Incident fractures were centrally adjudicated by review of radiology reports over 4.6 years. Correlations adjusted for weight and height were calculated between femoral neck BMD and D3Cr muscle mass. Across quartiles of D3Cr muscle mass/weight, proportional hazards models calculated hazard ratios (HRs) for any (n = 180); nonspine (n = 153); major osteoporotic fracture (n = 85); and hip fracture (n = 40) after adjustment for age, femoral neck BMD, recurrent fall history, and FRAX probability. Models were then adjusted to evaluate the mediating influence of physical performance (walking speed, chair stands, and grip strength). D3Cr muscle mass was weakly correlated with femoral BMD (r = 0.10, p < 0.001). Compared to men in the highest quartile, those in the lowest quartile of D3Cr muscle mass/weight had an increased risk of any clinical fracture (HR 1.8; 95% confidence interval [CI], 1.1–2.8); nonspine fracture (HR 1.8; 95% CI, 1.1–3.0), major osteoporotic fracture (HR 2.3; 95% CI, 1.2–4.6), and hip fracture (HR 5.9; 95% CI, 1.6–21.1). Results were attenuated after adjustment for physical performance, but associations remained borderline significant for hip and major osteoporotic fractures (p ≥ 0.05 to 0.10). Low D3Cr muscle mass/weight is associated with a markedly high risk of hip and potentially other fractures in older men; this association is partially mediated by physical performance.

Original languageEnglish (US)
Pages (from-to)1213-1220
Number of pages8
JournalJournal of Bone and Mineral Research
Issue number7
StatePublished - Jul 2022

Bibliographical note

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: R01 AG066671 (PMC ESO) and UL1 TR000128. Funding for the DCr muscle mass measure was provided by NIAMS (grant number R01 AR065268 (PMC)). GlaxoSmithKline provided in‐kind support by providing the D‐creatine dose and analysis of urine samples. 3 3

Publisher Copyright:
© 2022 American Society for Bone and Mineral Research (ASBMR).


  • bone-muscle interactions
  • epidemiology
  • fracture risk assessment
  • practice/policy-related issues
  • sarcopenia
  • skeletal muscle
  • systems biology - bone interactors
  • Bone Density
  • Prospective Studies
  • Risk Assessment
  • Humans
  • Risk Factors
  • Muscles
  • Male
  • Creatine
  • Absorptiometry, Photon
  • Aged, 80 and over
  • Hip Fractures/epidemiology
  • Aged
  • Osteoporotic Fractures/epidemiology

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


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