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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要骨质疏松性骨折与显着的发病率和死亡率及其美国经济负担相关预计到 2025 年将达到 200 亿美元。衰老会加速肌肉和骨骼的衰退，增加了解肌肉和骨骼如何在解剖学、机械和生化方面相互作用，以预防骨折风险。降低骨强度可以通过识别新的骨折风险筛查来深刻促进骨折预防诊断和治疗与年龄相关的肌肉骨骼衰退的干预目标。 (CT) 扫描对于评估区域肌肉和骨骼表型以识别老年人有很大希望具体来说，骨强度 – 3D 骨的 CT 和有限元建模评估。形态、骨矿物质密度 (BMD) 和皮质厚度——是骨折风险更强的预测指标仅 BMD。以肌肉、活动性和衰老研究 (SOMMA) 为基础，提出了 SOMMA-CT 辅助方案。该研究的独特定位是探索 CT 中大腿和躯干肌肉的特性（通过自动化和放射组学分析）、D3Cr 肌肉质量（D3-肌酸稀释）、肌肉性能以及循环肌肉- 骨串扰生物标志物，与髋部和脊柱骨强度的变化有关（2 例临床相关骨折） SOMMA 是一项前瞻性研究，探讨衰老相关的肌肉生物学对行动障碍的影响 (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具有成本效益的纵向设计增加了：1) 第 4 年的随访 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，以提取新的纵向数据肌肉和骨骼表型具体目标是： 1) 确定肌肉数量和成分（CT-）衍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组学纹理特征异质性；D3Cr 肌肉质量）与 4 年内髋部和脊柱骨强度的变化相关。 2) 确定肌肉性能（腿部伸肌比功率；4 米步态速度；完成 5 个椅子的时间）。站立）与 4 年衰老过程中髋部和脊柱骨强度的变化有关。肌骨串扰的生物标志物（肌因子：氨基丁酸；骨因子：CTX-1、P1NP）与横截面和纵向的骨强度，并测试这些生物标志物是否介导肌肉骨骼目标 1-2 中的关联科学前提是大腿和躯干肌肉退化会相关。随着髋部和脊柱骨强度的下降，循环生物标志物将提供以下机制的见解这项针对衰老队列的研究将增加我们对骨骼强度的影响。关于肌肉和骨骼之间的动态相互关系和串扰的知识这方面的新发现。该地区可能会影响全球超过 1.58 亿骨质疏松性骨折高风险的老年人。这项工作具有通过提高骨折风险预测能力来改变临床实践范式的巨大潜力筛选和识别肌肉和/或骨骼中的新表型，可用于预防骨折。