4.6 Article

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

Journal

JOURNAL OF BONE AND MINERAL RESEARCH
Volume 37, Issue 7, Pages 1213-1220

Publisher

WILEY
DOI: 10.1002/jbmr.4505

Keywords

skeletal muscle; sarcopenia; systems biology; bone interactors; bone-muscle interactions; epidemiology; practice; policy-related issues; fracture risk assessment

Funding

  1. National Institutes of Health
  2. National Institute on Aging (NIA)
  3. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  4. National Center for Advancing Translational Sciences (NCATS)
  5. NIH Roadmap for Medical Research [R01 AG066671, UL1 TR000128]
  6. NIAMS [R01 AR065268]

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The study investigates the relationship between total skeletal muscle mass and incident fractures. The findings indicate that low D3Cr muscle mass is associated with an increased risk of hip and potentially other fractures in older men, and this association is partially mediated by physical performance.
The relation between a novel measure of total skeletal muscle mass (assessed by D-3-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. (c) 2022 American Society for Bone and Mineral Research (ASBMR).

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