Bone tissue adapts to loads that are placed on it. For that reason, loss of functional weight-bearing and mobility (disuse) induces deterioration in weight-bearing skeletal sites, by disruption of the balance of bone formation and resorption towards net tissue loss. Ultimately, individuals that experience disuse (e.g. bedrest patients, spaceship crews) are threatened by increased risk of mechanical failure upon returning to regular weight bearing activities (reambulation) under traumatic or atraumatic loading. Furthermore, reambulation facilitates bone regain in smaller magnitude compared to tissue deterioration during disuse, and often individuals may not regain the entire bone tissue that was wasted during disuse. On the other hand, exogenous mechanical loading is anabolic to bone tissue. For example, organisms that are subjected to mechanical loading in vibratory form with low magnitude and high frequencies show increased bone formation that ultimately increases bone quantity and quality. As a non-invasive and non-pharmaceutical intervention, vibratory stimulus also induces very small deformations to bone tissue; therefore its applications are safe in mechanical perspective to bones of any size and shape, including those that suffer from extensive bone loss.

The overall objective of this dissertation was to determine: (1) the extent of coupling between morphological and micro-mechanical parameters during disuse and reambulation. Also if any of the parameters pertaining to either morphology or micro-mechanical properties can be used as a predictor of tissue response to upcoming disuse or reambulation (2) tissue- and cellular-level deterioration during disuse and if that could be prevented using high frequency low magnitude vibratory stimulus.

Results showed that disuse induced deterioration in bone morphology and micro-mechanical properties were not recovered for the similar duration of reambulation. Also, it was found that neither morphological nor micro-mechanical properties can fully predict bone's upcoming response to changes in mechanical environment. On the other hand, vibratory stimulus applied during disuse was found to be affecting bone marrow cells to maintain their osteogenic potential. Upon reambulation, the maintenance of osteogenic potential in bone marrow cells increased the bone mass that was regenerated.

Overall, results imply the importance of preventing disuse induced bone loss since regeneration of lost bone tissue may not always possible. However, in the absence of preventive measures, daily application of vibratory stimulus can increase bone tissue's capabilities of regeneration, offering a non-invasive and non-pharmaceutical remedy for disuse induced bone loss.