Fractures of the distal radius are a common consequence of falls in older adults. Exercise based interventions have been used to maintain and improve bone strength and prevent fall related fractures in older populations, based on evidence that bone adapts to the mechanical environment it experiences. This adaptive response takes place by bone modeling and remodeling, and is driven by the mechanical stimuli experienced by the bone. The magnitude of the adaptive response has been attributed to the characteristics of the mechanical stimulus in animals. However, the contribution of the different mechanical stimulus characteristics to the adaptive process is currently unknown in humans. The objective of this research was to understand the quantitative relationship of human bone to its mechanical environment, with the long term goal of designing and evaluating exercise interventions to prevent or slow bone loss that can lead to osteoporosis, and to improve fracture strength. A novel in-vivo wrist loading model was used to accomplish the objectives of this research. Methods for subject specific finite element model generation to predict the surface strains at the distal radius were validated with high accuracy (r=0.968, RMSE=11.1%), and were used to assess loading-induced bone strain in the subjects. An increase (or the prevention of a decrease) in ultra-distal radius size and mass was the primary adaptation response to the axial compression of the radius, and this response was more directly related to the strain magnitude than the force magnitude of the applied load. Additionally, small but significant correlations were observed between changes in bone mineral density and the mechanical measures of the applied loads at the local level within the bone. To our knowledge, this was the first time that the localized adaptation behavior of bone was tested in humans. In summary, we have developed an in vivo loading model of the human radius for the purpose of understanding the influence of mechanical environment on bone adaptation. In addition to its usefulness for exploring bone adaptation in humans, this research also acts as a step towards designing effective targeted mechanical interventions to increase (or prevent the decrease of) bone strength.