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: 10237325
• 负责人: JANE Ann CAULEY
• 金额: $ 35.96万
• 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/10237325
• 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大幅提高我们对骨之间相互作用的理解 “力学调节器理论”提出，骨骼会长期适应其形态和强度。 肌肉收缩施加的负荷 (1) 然而，肌肉和骨骼之间的双向信号传导。 的出现拓宽了这种关系，超越了纯粹的机械视角（2）。 通过 31P-Magnetic 检查肌肉产生 ATP 的最大能力 (ATP-max) 之间的关联 共振光谱 (31P –MRS)、股四头肌收缩量（MRI）、总肌肉质量 (TMM)（D3） 肌酸稀释度 (D3Cr)、功能性肌肉力量以及骨微结构和强度。 基本的科学前提是，与年龄相关的肌肉中产生 ATP 的能力下降，肌肉 体积、TMM 和功能能力会导致骨强度下降和骨微结构不良。 该提案建立在肌肉、活动性和衰老研究 (SOMMA) 的基础上，这是第一个关于肌肉的前瞻性研究 衰老旨在研究骨骼肌生物学和功能对主要活动障碍的影响。 建议扩展 SOMMA 以包括使用高分辨率的骨强度的重要骨骼测量 据我们所知，尚无研究将 ATP-max 联系起来。 股四头肌收缩量与体积 BMD、微结构和强度（根据评估的失效负荷 通过有限元分析）我们将在小梁和小梁中分别检查这些特征。 皮质室和承重（胫骨）和非承重（桡骨）骨部位。 测量 TMM 的方法仅限于参加男性骨质疏松性骨折研究（MrOS；平均 84 岁）。在 SOMMA 中，我们将能够研究 D3Cr TMM 与 HRpQCT 参数的关联。 建立 HRpQCT 与 TMM 和功能力量的关系。 爬楼梯的结果可能会确定可以改善两种组织的干预措施的目标结果 (2)。 在匹兹堡招募 438 名 SOMMA 受试者中的 400 名，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-肌肉相互作用。 目标 1：确定骨微结构、体积 BMD 和骨密度之间的关系 整体骨强度（失效负荷）以及小梁和皮质区室分别与体内 ATP- 最大、收缩肌体积和总骨骼肌质量 目标 2：确定关联。 爬楼梯测量的功能性肌肉力量与容积 HRpQCT 参数之间的关系 密度、微结构和强度 目标 3，探索性：探索关联中的性别差异。 在目标 1 和 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性的研究 肌肉的生物学特性、体积和功能力量及其与良好骨骼强度的关系 老年男性和女性的特征人口。