The influence of weight-bearing impact exercise and muscle strength on bone properties in healthy humans: sex- and age-specific effects

运动和肌肉力量在发展骨骼强度、提供机械保护和保存骨骼组织方面起着关键作用。骨重塑受施加在骨上的机械力的影响，包括地面反作用力和内部肌肉力。负重冲击运动，包括中等到高强度负荷（=2-4倍体重）和多向运动模式，被认为是诱导骨材料和结构特性变化的最有效策略。肌肉力量可以通过施加张力刺激骨骼形成来影响骨骼强度，因此有助于骨骼强度的调节（称为功能性肌肉-骨骼单位理论）。肌肉来源的生长因子也可能独立于机械负荷刺激骨形成，进一步证明了肌肉-骨关系的证据。尽管有大量证据支持肌肉质量与力量和骨强度替代物之间的正相关，但我们对哪些机械和生化肌肉相关因素解释了骨强度真实估计的最大差异的理解有限。同样，肌肉和骨骼大小和强度之间的关系可能在性别之间有所不同，并随着年龄的增长而发生显著变化，但我们不知道这些与性别和年龄相关的差异如何影响骨骼对合成代谢刺激（例如运动）的反应能力。因此，本提案的目的是研究负重冲击运动和肌肉力量对健康个体骨骼特性的影响，并确定其影响是否因性别和年龄而异。拟议的研究计划的目标是检查肌肉骨骼调节机制的性别差异，并比较其在年轻人和老年人中的决定因素。我们还将进行一项试点随机研究，比较12个月阻力训练加高冲击负荷干预与单独阻力训练和注意力对照组。这些研究将为负重冲击运动和肌肉生成负荷对人类骨骼强度、几何形状和结构的独立和相互作用提供新的见解。结合量化骨材料和结构特性的专业措施，评估肌肉的机械和生化因素，我们的目标是为肌肉在骨代谢调控中的作用以及对骨强度的下游影响提供新的证据。这些研究的结果将增强我们对男性和女性在一生中对日常生活和运动中不同压力源的骨骼反应的基本理解。

Exercise and muscle strength play a critical role in developing bone strength, providing mechanical protection, and preserving skeletal tissue. Bone remodeling is influenced by mechanical forces applied to bone, including ground reaction forces and internal muscle forces. Weight-bearing impact exercise, involving moderate-to-high magnitude loads (=2-4 times body weight) and multidirectional movement patterns, is considered the most effective strategy for inducing changes in bone material and structural properties. Muscle forces can influence bone strength by applying strains to stimulate bone formation, and therefore contribute to the regulation of bone strength (known as the functional muscle-bone unit theory). Muscle-derived growth factors may also stimulate bone formation independent of mechanical loading, further demonstrating evidence of a muscle-bone relationship. Despite substantial evidence in support of a positive association between muscle mass and strength and surrogates of bone strength, we have limited understanding of which mechanical and biochemical muscle-related factors explain the most variability in true estimates of bone strength. As well, the relationship between muscle and bone size and strength may differ between sexes and change significantly with age, yet we do not know how these sex- and age-related differences impact the capacity of bone to respond to anabolic stimuli (e.g., exercise). Therefore, the purpose of this proposal is to examine the influence of weight-bearing impact exercise and muscle strength on bone properties in healthy individuals and to determine whether their effects differ between sexes and with age. The goals of the proposed research program are to examine the sex differences in the muscle-bone regulatory mechanism as well as compare its determinants in younger and older adults. We will also conduct a pilot randomized study comparing a 12-month resistance training plus high-impact loading intervention versus resistance training alone and an attentional control group. These studies will provide novel insight into the independent and interacting roles of weight-bearing impact exercise and muscle-generating loading on bone strength, geometry, and structure in humans. Combining specialized measures to quantify bone material and structural properties with assessments of mechanical and biochemical muscle factors, we aim to provide new evidence on the role of muscle in governing the regulation of bone metabolism and the downstream effects on bone strength. The results from these studies will enhance our fundamental understanding of bone responses to different stressors of daily life and exercise in men and women across the lifespan.