Computed tomography muscle size and composition associations with hip and spine bone strength over 4 years: SOMMA-CT

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PROJECT SUMMARY Osteoporotic fractures are associated with significant morbidity and mortality, and their U.S. economic burden is projected to reach $20 billion by 2025. Aging accelerates the decline of both muscle and bone, increasing fracture risk. Understanding how muscle and bone interact anatomically, mechanically, and biochemically to reduce bone strength could profoundly advance fracture prevention by identifying new fracture risk screening and intervention targets to diagnose and treat age-related musculoskeletal decline. Computed tomography (CT) scans hold great promise for assessing regional muscle and bone phenotypes to identify older adults at high risk of fracture. Specifically, bone strength – a CT and finite element modeling assessment of 3D bone morphology, bone mineral density (BMD), and cortical thickness – is a stronger predictor of fracture risk than BMD alone. Building on the Study of Muscle, Mobility & Aging (SOMMA), the proposed SOMMA-CT ancillary study is uniquely positioned to explore how thigh and trunk muscle properties from CT (via automated and radiomic analysis), D3Cr muscle mass (D3-creatine dilution), muscle performance, as well as circulating muscle- bone crosstalk biomarkers, relate to changes in bone strength at the hip and spine (2 clinically-relevant fracture sites). SOMMA is a prospective study examining aging-related muscle biology contributions to mobility disability (R01 AG059416). This ancillary study in 360 SOMMA older men and women (ages 70-94) will employ an efficient and cost-effective longitudinal design that adds: 1) a 4th-year follow-up CT scan and blood draw, and 2) advanced processing of baseline and 4-year CT scans and blood samples to extract new longitudinal muscle and bone phenotypes. Specific Aims are to: 1) Determine if muscle quantity and composition (CT- derived thigh and trunk muscle area, muscle density, intermuscular fat, and radiomic texture features of muscle heterogeneity; D3Cr muscle mass) are associated with changes in hip and spine bone strength over 4 years of aging. 2) Determine if muscle performance (leg extensor specific power; 4-m gait speed; time to complete 5 chair stands) is associated with change in hip and spine bone strength over 4 years of aging. We will also explore how biomarkers of muscle-bone crosstalk (myokines: aminobutyric acids; osteokines: CTX-1, P1NP) relate to bone strength both cross-sectionally and longitudinally, and test if these biomarkers mediate the muscle-bone associations in Aims 1-2. The scientific premise is that thigh and trunk muscle degeneration will be associated with declining hip and spine bone strength, and that circulating biomarkers will offer mechanistic insights on muscle-bone crosstalk contributors to bone strength. This investigation in an aging cohort will increase our knowledge of the dynamic interrelationships and crosstalk between muscle and bone. New discoveries in this area could impact over 158 million older adults worldwide who are at high risk of osteoporotic fracture. This work has strong potential to shift clinical practice paradigms by improving predictive power in fracture risk screening and identifying new phenotypes in muscle and/or bone which could be targeted to prevent fracture.