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

4 年来计算机断层扫描肌肉大小和成分与髋部和脊柱骨强度的关系：SOMMA-CT

• 批准号: 10741630
• 负责人: Ashley Weaver
• 金额: $ 79.57万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-05 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10741630
• 关键词: 3-Dimensional; Acceleration; Adult; Age; Aging; American; Aminobutyric Acids; Anatomy; Ancillary Study; Area; Biochemical; Biological Assay; Biological Markers; Biology; Biomedical Engineering; Biometry; Blood; Blood specimen; Body mass index; Bone Density; Clinical; Creatine; Cyclophosphamide; Data; Detection; Diagnosis; Dual-Energy X-Ray Absorptiometry; Economic Burden; Elderly; Elements; Extensor; Fatty acid glycerol esters; Fracture; Gait speed; Heterogeneity; Hip region structure; Intervention; Investigation; Knowledge; Leg; Longitudinal Studies; Measures; Mechanics; Mediating; Mediation; Modeling; Morbidity - disease rate; Morphology; Muscle; Muscular Atrophy; Musculoskeletal; Open Fractures; Osteoporosis; Patients; Performance; Phenotype; Population; Positioning Attribute; Prevention; Property; Prospective Studies; Research; Research Personnel; Risk; Sampling; Scanning; Site; Skeletal Muscle; Testing; Texture; Thick; Thigh structure; Time; Treatment Efficacy; Vertebral column; Woman; Work; X-Ray Computed Tomography; age related; aging population; biobank; bone; bone health; bone loss; bone mass; bone strength; circulating biomarkers; clinical care; clinical practice; clinically relevant; cohort; cost; cost effective; density; disability; follow-up; forest; fracture risk; gamma-Aminobutyric Acid; high dimensionality; high risk; hip bone; human old age (65+); improved; insight; longitudinal design; men; mortality; multidisciplinary; muscle aging; muscle degeneration; muscle form; novel; older men; older women; osteoporosis with pathological fracture; performance tests; prevent; primary outcome; radiomics; remediation; sarcopenia; screening; therapeutic target; uptake

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.

项目总结 骨质疏松性骨折与严重的发病率和死亡率及其在美国的经济负担有关 预计到2025年将达到200亿美元。衰老会加速肌肉和骨骼的衰退，增加 骨折风险。了解肌肉和骨骼如何在解剖、机械和生化方面相互作用 通过识别新的骨折风险筛查，降低骨强度可以深刻地促进骨折预防 以及诊断和治疗与年龄相关的肌肉骨骼衰退的干预目标。计算机断层扫描 (CT)扫描在评估区域肌肉和骨骼表型以识别老年人方面大有可为 骨折的风险很高。具体地说，骨强度--3D骨的CT和有限元建模评估 形态、骨密度(BMD)和皮质厚度--是骨折风险的更强预测因子 只有BMD。在肌肉、行动能力和衰老(Somma)研究的基础上，拟议的Somma-CT辅助 这项研究的独特之处在于探索如何通过CT(通过自动化和 放射学分析)、D3Cr肌肉质量(D3-肌酸稀释)、肌肉性能以及循环肌肉- 骨串扰生物标记物，与髋部和脊柱骨强度的变化有关(2个临床相关的骨折 站点)。Somma是一项前瞻性研究，旨在研究与衰老相关的肌肉生物学对行动能力障碍的贡献。 (R01 AG059416)。这项针对360名Somma老年男性和女性(70-94岁)的辅助研究将采用 高效且经济实惠的纵向设计，增加了：1)4年随访CT扫描和抽血，以及 2)对基线和4年CT扫描和血液样本进行高级处理，以提取新的纵向 肌肉和骨骼的表型。具体目标是：1)确定肌肉数量和组成(CT- 派生的大腿和躯干肌肉面积、肌肉密度、肌间脂肪和肌肉的放射状纹理特征 异质性；D3Cr肌肉质量)与4年来髋部和脊柱骨强度的变化有关 衰老。2)确定肌肉性能(腿部伸肌比功率；4米步速；完成5个椅子的时间 站立)与4年后髋部和脊柱骨强度的变化有关。我们还将探索 肌肉-骨骼串扰的生物标志物(肌肉因子：氨基丁酸；骨因子：CTX-1、P1NP)与 横截面和纵向的骨强度，并测试这些生物标记物是否调节肌肉-骨骼 AIMS 1-2中的协会。科学的前提是大腿和躯干肌肉的退变将会相关 随着髋骨和脊柱骨强度的下降，循环中的生物标记物将提供对 肌肉-骨骼相声对骨骼力量的贡献。这项在老龄化队列中的调查将增加我们的 了解肌肉和骨骼之间的动态相互关系和串扰。在这方面的新发现 该地区可能会影响到全世界超过1.58亿的老年人，他们面临着骨质疏松性骨折的高风险。这 这项工作有很大的潜力通过提高骨折风险的预测能力来改变临床实践范式 筛选和确定肌肉和/或骨骼中可作为预防骨折靶点的新表型。