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: 9901926
• 负责人: JANE Ann CAULEY
• 金额: $ 41.27万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901926
• 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大提高我们对骨骼之间相互作用的理解