Augmentation of Peak Bone Mass

与骨质疏松性骨折相关的主要风险因素之一是在成年早期未能获得足够的骨量。运动具有非侵入性骨增长的巨大潜力，但一般的运动方案仅最低限度地提高骨量超过正常水平，并依赖于高冲击，高幅度的负载来实现这些骨增益。最近，我们发现，在低幅度负荷方案的每个负荷循环之间插入短暂的休息时间足以将方案从不影响骨细胞群的方案转变为有效成骨的信号。因此，该方案可能特别适合于在需要增强骨特性但高冲击运动不可行的情况下应用。根据我们的初步数据和文献综述，我们假设，低幅度，休息插入，骨骼生长过程中开始的机械负荷将提高成年哺乳动物的皮质骨性能。为了探索这一假设，我们将利用我们最近开发的非侵入性小鼠胫骨加载装置。设计了一系列五个特定目标，以确定静息插入、低幅度载荷是否可用于在雌性C57BLI6J小鼠中构建和维持增强的胫骨皮质骨特性。这些研究最终达到了我们的最终目标，我们将评估由剩余插入负载诱导的增强的皮质骨特性是否足以抵消由老化和雌激素消耗引起的退化。在基本水平上，这些研究将提供关于年轻生长的骨骼如何对机械负荷作出反应的独特见解，并将提供一个基线信息，我们将在未来开始探索特定的遗传改变（例如，通过转基因或敲除小鼠）影响骨中的机械传导。在应用水平，结果，其中休息插入，低幅度，非侵入性负载显着增加和保持小鼠皮质骨的属性将放置我们的小组在位置开始，以探讨这一概念在人类受试者的疗效。

One of the primary risk factors associated with osteoporotic fractures is the failure to achieve sufficient bone mass during early adulthood. Exercise holds substantial potential for non-invasive bone accretion, but general exercise protocols only minimally enhance bone mass over normal levels and rely upon high impact, high magnitude loading to achieve these bone gains. Recently, we found that inserting a brief rest interval between each load cycle of a low magnitude loading regimen is sufficient to transform the protocol from one that does not influence bone cell populations into a signal that is potently osteogenic. This regimen may therefore be particularly amenable to application in conditions where enhanced bone properties are desirable, but high impact exercise is not feasible. Based upon our preliminary data and a review of the literature, we hypothesize that low magnitude, rest-inserted, mechanical loading initiated during skeletal growth will enhance the cortical bone properties of adult mammals. To explore this hypothesis, we will capitalize on our recently developed non-invasive murine tibia loading device. A series of five Specific Aims have been designed to determine if rest-inserted, low magnitude loading can serve to build and maintain augmented tibial cortical bone properties in female C57BLI6J mice. The studies culminate with our final Aim, in which we will assess whether enhanced cortical bone properties induced by the rest-inserted loading are sufficient to counteract the degradation caused by aging and estrogen depletion. At a basic level, these studies will provide unique insight toward how young growing bones respond to mechanical loading, and will provide a baseline of information from which we will, in the future, begin to explore how specific genetic alterations (e.g., via transgenic or knockout mice) affect mechanotransduction in bone. At the applied level, an outcome in which rest-inserted, low magnitude, non-invasive loading significantly augments and maintains murine cortical bone properties would place our group in position to begin to explore the efficacy of this concept in human subjects.