Muscle quantity, quality, function, and biomarker associations with longitudinal preservation of bone microarchitecture and bone strength in older adults - the long-term goal of the project is to…

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) awarded the University of Pittsburgh a $1.61 million Project Grant (CFDA 93.846: Arthritis, Musculoskeletal and Skin Diseases Research) beginning September 15, 2025, and concluding August 31, 2029. This research initiative examines the longitudinal associations between muscle characteristics and bone health preservation in older adults. The project leverages the Study of Muscle, Mobility and Aging (SOMMA), a prospective cohort of 294 participants aged 76+ years in Pittsburgh, Pennsylvania. The research will deliver comprehensive scientific analysis of muscle energetics (ATP maximum capacity via 31P-magnetic resonance spectroscopy), muscle mass (via D3 creatine dilution), quadriceps volume (via MRI), muscle function (strength and power), and myokine biomarkers (D-, L-BAIBA, GABA, and L-AABA aminobutyric acids) with respect to 5-year longitudinal changes in bone density, microarchitecture, and strength outcomes measured by high-resolution peripheral quantitative computed tomography.

The project incorporates two primary research aims: (1) determining associations between muscle energetics, mass, volume, and function with 5-year changes in bone parameters; and (2) evaluating whether specific myokines are associated with cross-sectional and longitudinal changes in bone health. Sub-awards to Wake Forest University Health Sciences (March 16, 2026) and California Pacific Medical Center Research Institute/Sutter Bay Hospitals (September 15, 2025) will provide collaborative research infrastructure, data analysis, and study coordination support to advance understanding of the mechanistic connections between muscle decline and age-related bone loss through both mechanical loading and biochemical signaling pathways.

Muscle quantity, quality, function, and biomarker associations with longitudinal preservation of bone microarchitecture and bone strength in older adults - the long-term goal of the project is to substantially improve the understanding of how muscle impacts bone loss. Muscle and bone may be connected via mechanostat loading, as bone adapts its morphology and strength from muscle contraction, or by bidirectional muscle-bone signaling, which occurs beyond a purely mechanical perspective. We propose to examine comprehensive muscle associations of maximal capacity of muscle to generate ATP (ATP max) by 31P-magnetic resonance spectroscopy (31P-MRS), quadriceps (THIGH) contractile volume by MRI, total muscle mass by D3 creatine dilution (D3CR), muscle function (strength and power), and myokines with 5-year longitudinal change in bone density, microarchitecture and strength outcomes. The underlying scientific premise is that age-related decreases in the muscle ATP, volume, total mass, function and myokines lead to declines in bone density, microarchitecture and strength. This project leverages the recent renewal of the study of muscle, mobility and aging (SOMMA), the first prospective study of muscle aging, which evaluates the role of skeletal muscle to major mobility disability. In the first follow-up, we added measures of bone density, microarchitecture and strength (failure load by finite element analysis) using high-resolution peripheral quantitative computed tomography (HR-PQCT) in 327/385 (85%) of men and women (76+5 years; 61% women) in pittsburgh, PA. We anticipate 294 will repeat an HR-PQCT scan at visit 6 to determine: aim 1, muscle energetics, mass, volume, and function (power, strength) associations with 5-year change in HR-PQCT bone density, microarchitecture, and strength; and aim 2, if myokines (D-, L-baiba, gaba, and L-aaba aminobutyric acids) are associated with cross-sectional and 5-year change in HR-PQCT bone parameters. We will examine trabecular and cortical bone parameters in a weight bearing (TIBIA) and non-weight bearing (RADIUS) bone site, adjust for key risk factors (e.g., BMI, physical activity) and evaluate if bone biomarkers (CTX-1, P1NP) explain associations. To our knowledge, no studies have linked ATP-max and THIGH contractile volume to longitudinal changes volumetric BMD, microarchitecture and strength, or evaluated D3CR and these longitudinal HR-PQCT changes on both older men and women. Our SOMMA ancillary study offers a cost-efficient opportunity to investigate muscle- bone longitudinal change using state-of-the-art measures. We will be the first to study novel properties of muscle energetics, mass, volume and function, and myokines, in association with changes in bone strength and microarchitecture in a well-characterized population of older men and women. We may potentially identify targeted muscle pathways that improve bone tissue.