Despite the use of exercise countermeasures, bone mineral density (BMD) and bone strength changes which have been shown to occur at a rate of ~ ‐1 to ‐3% per month are a potentially serious medical scenario that may lead to increased fracture risk. These decrements in bone are likely due to the decrease in mechanical loading experienced by the musculoskeletal system while living on‐orbit.

The primary objective of this dissertation is to shed light on the effects of altered gravity environments on the mechanobiology of bone. This objective is explored through surrogate measures using the bedrest model of bone loss, direct measures on‐ board the International Space Station (ISS) and theoretical calculations using Finite Element (FE) and musculoskeletal modeling techniques.

Through the enhancement of previous algorithms relating daily mechanical loading to bone homeostasis, we have developed the Enhanced Daily Load stimulus (EDLS) as a method of prescribing exercise in a “dose” based manner during bedrest. We were able, on average, to prevent bone loss in exercise subjects. To expand the examination of the efficacy of exercise countermeasures beyond the limitations of BMD measures, we developed subject specific, voxel‐ and Computed Tomography (CT)‐based Finite Element (FE) models of the proximal femur. With these models, we were able to account for the 3D geometry of the bone and calculated bone strength and show that, on average, exercise subjects had lower decrements in bone strength than control subjects.

The FE models used to examine strength changes during space flight use boundary conditions that are in the context of Earth gravity (1g), thus these models are likely not relevant when examining fracture risk in crewmembers living on other planets or in reduced gravity. Therefore, we combined FE and musculoskeletal modeling to develop a preliminary modeling framework that would allow the examination of tissue level stresses that may occur in the femur during a more operationally relevant movement that may occur in these altered gravity environments.

In chapter 5, we examined the loading that actually occurs during exercise on board the ISS. We used in‐shoe force sensors to measure the envelope of lower extremity mechanical loads that the available exercise devices could generate. We were able to provide a benchmark that will enable future researchers to judge whether or not new generations of exercise countermeasures are superior to those used at the time the data for the present experiments were collecte