Augmentation of Peak Bone Mass

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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.