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

该项目的长期目标是大大提高我们对骨与骨之间相互作用的理解。 和肌肉“机械稳定器理论”提出，骨适应其形态和强度，以长期 肌肉收缩产生的负荷（1）。然而，肌肉和骨骼之间的双向信号， 已经出现了拓宽的关系超越了一个纯粹的机械的角度（2）。我们建议 通过31 P-磁共振成像检查肌肉产生ATP的最大能力（ATP-max） 磁共振波谱（31 P-MRS）、MRI测量的四头肌收缩量、D3测量的总肌肉质量（TMM） 肌酸稀释（D3 Cr）和功能性肌肉力量以及骨微结构和强度。的 基本的科学前提是，年龄相关的能力下降，产生ATP的肌肉，肌肉 体积、TMM和功能功率导致骨强度降低和骨微结构不良。这 该提案建立在肌肉，流动性和衰老研究（SOMMA）的基础上，这是第一个肌肉前瞻性研究 老化的目的是研究骨骼肌生物学和功能对主要活动能力残疾的贡献。我们 建议扩展SOMMA，以包括使用高分辨率测量骨强度的重要骨骼措施 外周定量计算机断层扫描（HRpQCT）。据我们所知，没有研究表明 和股四头肌收缩体积与体积BMD、微结构和强度（评估的失效载荷 有限元分析）。我们将全面和单独地检查这些特征， 皮质隔室以及承重（胫骨）和非承重（桡骨）骨部位。D3Cr 测量TMM的方法仅限于男性骨质疏松性骨折研究中招募的男性（MrOS;平均值 年龄84岁）。在SOMMA中，我们将能够研究D3 Cr TMM与HRpQCT参数的相关性， 更广泛的男女年龄组。建立HRpQCT与TMM和功能功率的关系 从爬楼梯可以确定干预的目标结果，可以改善两种组织（2）。我们将 在匹兹堡招募了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骼-肌肉相互作用。我们建议 以下具体目的：目的1：确定骨微结构、体积BMD和 整体骨强度（失效载荷）以及分别在骨小梁和皮质间室中与体内ATP- 最大值、收缩肌体积和总骨骼肌质量。目标2：确定关联 通过爬楼梯测量的功能性肌肉力量与容积的HRpQCT参数之间的关系 密度、微结构和强度。目的3，探索性：探索关联中的性别差异 研究目的1和2。总体影响：这项SOMMA辅助研究将是第一项研究新型 肌肉生物学特性，体积和功能功率及其与骨强度的关系， 老年男性和女性的特征人口。

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.