Bone microarchitecture and bone strength relationships to muscle quantity, quality and function in older adults

老年人骨微结构和骨强度与肌肉数量、质量和功能的关系

• 批准号: 10616465
• 负责人: JANE Ann CAULEY
• 金额: $ 37.02万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-18 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10616465
• 关键词: Age; Aging; Ancillary Study; Biology; Biopsy; Bone Density; Characteristics; Clinical; Complex; Creatine; Data; Elderly; Enrollment; Failure; Fatty acid glycerol esters; Finite Element Analysis; Fracture; Funding; Funding Opportunities; Goals; Hip region structure; Individual; Intervention; Investigation; Lead; Link; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mechanics; Methods; Mission; Morphology; Movement; Muscle; Muscle Contraction; Musculoskeletal Diseases; Musculoskeletal System; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Observational Study; Older Population; Outcome; Participant; Peripheral; Physical activity; Prevention; Process; Property; Prospective Studies; Radial; Research Support; Resolution; Resources; Science; Sex Differences; Signal Transduction; Site; Skeletal Muscle; Testing; Thick; Time; Tissues; Weight-Bearing state; Woman; X-Ray Computed Tomography; age group; age related; bone; bone strength; cost efficient; density; disability; improved; in vivo; men; muscle aging; muscle form; muscle strength; novel; older men; older women; osteoporosis with pathological fracture; quadriceps muscle; recruit; sex; skeletal; theories; tibia

The long-term goal of the project is to substantially improve our understanding of the interaction between bone and muscle. The “mechanostat theory” proposes that bone adapts its morphology and strength to long-term loads exerted by muscle contraction (1). However, the bidirectional signaling between muscle and bone that has emerged broadens the relationship beyond that of a purely mechanical perspective (2). We propose to examine the association between maximal capacity of muscle to generate ATP (ATP-max) by 31P-Magnetic Resonance Spectroscopy (31P –MRS), quadriceps contractile volume by MRI, total muscle mass (TMM) by D3 creatine dilution (D3Cr), and functional muscle power and bone microarchitecture and strength. The underlying scientific premise is that age related declines in the capacity to generate ATP in muscle, muscle volume, TMM and functional power lead to decreases in bone strength and poor bone microarchitecture. This proposal builds on the Study of Muscle, Mobility and Aging (SOMMA), the first prospective study of muscle aging aimed to study the contributions of skeletal muscle biology and function to major mobility disability. We propose to extend SOMMA to include important skeletal measures of bone strength using high-resolution peripheral quantitative computed tomography (HRpQCT). To our knowledge, no studies have linked ATP-max and quadriceps contractile volume to volumetric BMD, microarchitecture and strength (failure load as assessed by finite element analysis). We will examine these characteristics globally and separately in the trabecular and cortical compartments and in a weight bearing (tibia) and non-weight bearing (radius) bone site. The D3Cr method of measuring TMM is limited to men enrolled in the Osteoporotic Fractures in Men study (MrOS; mean age 84 yrs). In SOMMA we will be able to study the D3Cr TMM associations with the HRpQCT parameters on a wider age group of both men and women. Establishing HRpQCT relationships to TMM and functional power from the stair climb may identify target outcomes for interventions that can improve both tissues (2). We will recruit 400 of the 438 SOMMA subjects in Pittsburgh. Our proposal offers a cost-efficient opportunity to investigate the bone-muscle interaction in older adults using state-of-the-art measurements. We propose the following specific aims: Aim 1: To determine the association of bone microarchitecture, volumetric BMD, and bone strength (failure load) globally and in the trabecular and cortical compartments separately to in-vivo ATP- max, contractile muscle volume and total skeletal muscle mass. Aim 2: To determine the association between functional muscle power as measured by the stair climb to HRpQCT parameters of volumetric density, microarchitecture and strength. Aim 3, Exploratory: To explore sex differences in the associations studied in Aims 1 and 2. OVERALL IMPACT: This SOMMA ancillary study will be the first to study novel properties of muscle biology, volume, and functional power and their relationships to bone strength in a well- characterized population of older men and women.

该项目的长期目标是大幅提高我们对骨骼之间相互作用的理解。 和肌肉。“恒力理论”认为，骨骼的形态和强度能够适应长期的变化。 肌肉收缩所施加的负荷(1)。然而，肌肉和骨骼之间的双向信号传递 已经出现了超越纯粹机械观点的关系(2)。我们建议 用31P-Magic检查肌肉最大生成ATP能力(ATP-max)之间的关系 磁共振波谱(31P-MRS)，MRI测量股四头肌收缩体积，D3测量总肌量(TMM) 肌酸稀释度(D3Cr)、功能性肌力、骨微结构和力量。这个 潜在的科学前提是与年龄相关的肌肉、肌肉中产生三磷酸腺苷的能力下降 体积、TMM和功能功率导致骨强度下降，骨微结构不良。这 该提案建立在肌肉、活动能力和衰老研究(Somma)的基础上，这是第一项关于肌肉的前瞻性研究 衰老的目的是研究骨骼肌生物学和功能在主要活动障碍中的作用。我们 建议将Somma扩展到包括使用高分辨率的骨骼强度的重要骨骼测量 外周定量计算机断层扫描(HRpQCT)。据我们所知，没有研究将三磷酸腺苷-最大 股四头肌收缩体积与体积骨密度之比、微结构和强度(失效负荷评估 通过有限元分析)。我们将在全球范围内和在小梁和 皮质室和承重(胫骨)和非承重(桡骨)骨部位。D3Cr型 测量TMM的方法仅限于参加男性骨质疏松性骨折研究(MROS；Mean)的男性 84岁)。在Somma，我们将能够研究D3CrTMM与HRpQCT参数之间的关系 男性和女性都有更广泛的年龄段。建立HRpQCT与TMM和职能权力的关系 从楼梯上爬可以确定可以改善两个组织的干预措施的目标结果(2)。我们会 在匹兹堡招募438名索玛受试者中的400人。我们的建议提供了一个具有成本效益的机会 使用最先进的测量方法研究老年人的骨骼-肌肉相互作用。我们建议 以下具体目标：目标1：确定骨微结构、体积骨密度和骨密度之间的关系 骨强度(破坏负荷)在骨小梁和皮质室分别与体内的ATP- 最大值、收缩肌体积和骨骼肌总质量。目标2：确定两者之间的联系 功能肌力以楼梯爬高到HRpQCT的容积参数测量 密度、微架构和强度。目标3，探索性：探索关联中的性别差异 在目标1和目标2中研究。总体影响：这项Somma辅助研究将是第一个研究小说 井中肌肉生物学、体积和功能力量的特性及其与骨强度的关系- 以老年男女为特征的人群。