Mechanical loading conditions are known to influence the fracture healing process. Therefore, the way that daily activities such as gait are performed directly effect musculoskeletal loading. The purpose of this study has been to explore the relationships between natural, preferred loading and pathological loading during fracture healing and their effect on biomineralization of the fracture callus and surrounding muscles. Within this research, there were three specific aims. The first was to create a novel model for prediction of biomineralization following fracture. The other two specific aims were associated with two separate studies, exploring the following hypotheses:​ 1. Abnormal loading, through altered gait, following fracture will inhibit biomineralization and, therefore, healing. 2. A decrease in oxidative capacity is associated with inactivity during fracture healing.

A combination of experimental approaches and mathematical modeling was used in the three related but separate studies. These studies resulted in a new analysis methodology which quantifies three-dimensional biomineralization of a fracture callus, an analysis of adaptations in muscle mitochondrial content to gain insight into how inactivity is reflected in the physiology of the muscles surrounding the fracture site, and development of a dynamic model which solves for the load vector on the fracture callus due to musculoskeletal loading during fracture healing. The load vector is the input for a finite element analysis on fracture callus geometry determined via synchrotron xray-based microtomography. Physiologically-realistic inputs for the model have been measured experimentally. This approach incorporates a forward- dynamic biomineralization function to mimic the healing;​ process.

Through the first study, a new quantity, the “mineralization vector”, has been defined. Loading treatments can be distinguished in terms of their effect on biomineralization of a fracture callus with the use of the mineralization vector calculation. We conclude from the second study that femoral fracture, patellar tenotomy, or both significantly reduce citrate synthase activity in the knee flexors, indicating a reduction in these muscles ability to produce force. Tenotomy, regardless of fracture, seems to be a major factor in maintaining a decreased citrate synthase activity, whereas the effects of fracture alone were more transient. In the third study, the approach of combining technologies and modeling techniques was validated and shown to be a viable method of simulating and visualizing aspects of fracture rehabilitation. Together, the results of these three studies contribute to the visualization and prediction of biomineralization of the fracture callus and muscular adaptation during fracture healing, useful for optimizing treatm ent following fracture.