Physical activity is important for the overall health of individuals. Impacts that occur when the foot hits the ground have the potential to be an influential factor in both the etiology of overuse injury and the promotion of bone health. Stress injury to bone is considered the ultimate overuse injury and accounts for the nearly one fourth of injuries in active populations. This dissertation evaluates bone loading in three ways: in vivo strain gage measurement, a combination of experimental and modeling techniques, and tibial accelerometry. Emphasis was placed on the clinical implication of findings from such techniques on the treatment and prevention of bone stress injury. The first study assessed the influence of orthotics on bone strain. The results of this study indicated that bone strain and strain rates were minimized with the use of orthotics. Secondly, the use of custom orthotics was more effective in minimization of strains and strain rates than semi-custom orthotics. The second and third studies used a combination of experimental data and musculoskeletal modeling to estimate combined loading, internal bone forces, moments and stresses. The findings from these studies were 1) the tibia is predominately undergoes in-phase loading of axial and torsional loads 2) gait mechanics can independently influence bone stresses and stress rates in the distal tibia 3) runners with a history of stress fracture demonstrate only moderately elevated internal bone forces and moments in the distal tibia. The final study of this dissertation evaluated injury more globally and assessed variability of stride time output. The patterned behavior of stride time variability was sensitive to fatigue and group differences. The results of these studies add to an ever growing body of knowledge of gait and injury and suggest that the internal loads of bone can be influenced by external support and gait mechanics. However, the multifactoral nature of injury cannot be ignored in the study of stress fracture. Additionally, fatigue and injury status play a role in the neuromuscular control system output during running and influence overall gait dynamics.