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: 10019331
• 负责人: JANE Ann CAULEY
• 金额: $ 39.79万
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019331
• 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; radius bone structure; 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实质上提高我们对骨骼相互作用的理解 和肌肉。骨头将其形态和力量适应长期的“机械仪表理论”提案 肌肉收缩执行的负载（1）。但是，肌肉和骨骼之间的双向信号传导 出现的范围扩大了纯粹的机械观点的关系（2）。我们建议 检查肌肉最大能力通过31p-magnetic产生ATP（ATP-MAX）的关联 共振光谱（31p –mrs），MRI的股四头肌收缩量，D3总肌肉质量（TMM） 肌酸稀释（D3CR）以及功能性肌肉力量和骨微体系结构和力量。这 基本的科学前提是，与年龄相关的肌肉，肌肉的ATP的能力下降 体积，TMM和功能功率导致骨骼强度和骨微体系结构差的下降。这 提案建立在肌肉，流动性和衰老（SOMMA）的基础上，这是肌肉的首次前瞻性研究 衰老旨在研究骨骼肌生物学和功能对主要活动性残疾的贡献。我们 提议扩展somma，以使用高分辨率来包括重要的骨骼强度骨骼测量 外围定量计算机断层扫描（HRPQCT）。据我们所知，没有研究与ATP-MAX联系在一起 股四头肌的股四头肌量为体积BMD，微结构和强度（评估的故障负载 通过有限元分析）。我们将在小梁和 皮质隔室，体重轴承（胫骨）和非重量轴承（半径）骨位点。 D3CR 测量TMM的方法仅限于在男性研究中入学的男性（MROS；平均值；平均值； 年龄84岁）。在Somma，我们将能够研究与HRPQCT参数的D3CR TMM关联 男女的更广泛年龄段。建立与TMM和功能能力的HRPQCT关系 从楼梯上攀登可以确定可以改善两种组织的干预措施的目标结果（2）。我们将 在匹兹堡的438名Somma受试者中有400名招募400名。我们的建议提供了一个成本效益的机会 使用最先进的测量结果研究老年人的骨肌肉相互作用。我们建议 以下特定目的：目标1：确定骨微结构，体积BMD和 骨强度（故障负荷）在全球和小梁和皮质室中分别以体内到体内ATP- 最大，收缩肌肉体积和总骨骼肌质量。目标2：确定关联 在功能性肌肉力量之间通过楼梯爬升到体积的HRPQCT参数 密度，微结构和力量。目标3，探索性：探索协会的性别差异 在目标1和2中进行了研究。总体影响：这项SOMMA辅助研究将是第一个研究新颖的研究 肌肉生物学，体积和功能能力的特性及其与骨骼强度的关系 年龄较大的男人和女人的人口。