An Agent-based Model for Evaluating Cellular Mechanisms of Bone Remodeling

iii Acknowledgements I would like to thank Dr. Hollinger for his financial support, academic knowledge, and enthusiasm for this project. Without his help, none of this thesis would exist. I `would also like to thank my committee—Dr. Dr. Lance Davidson—for all their expert advice and tireless patience. It requires a sincere devotion to education to teach a biochemist like myself to setup and analyze a model of this complexity. Every instance of the correct technique or method of analysis is a sign of their help. I also wish to thank my family for all their support and kindness. This project is a reflection of all the Sutton's, Peatman's, and Schutte's love for learning and knowledge. I would not still be in school, nor would I have wandered so far into the medically unknown without your influence and support. Life might have been easier sticking to what I already knew or doing what we knew could be done, but what kind of an adventure would that be? A giant thanks goes out to all my friends and labmates. This would not have been nearly as fun without you. Amy Donovan in particular—I think you've edited everything I've had to write (which is fantastic since you are the best scientific editor I've ever met); thank you. Ivan Jager—thank you for being marvelous, for putting up with the thesis sucking away all our free time, for setting up the linux cluster (seriously, that would have taken me days), and for lovingly teasing me into writing scripts for all the data manipulations. I would have been here till 2013 with those eight thousand spreadsheets. Lastly, I'd like to thank my God for challenging me to think deeper, for being such a solid center, and for making me into a better person than I am. iv v Abstract In this thesis I present a mechanistic computational model of the cells and processes involved in bone remodeling. Despite decades of progress uncovering the mysteries of bone biology and developing a wide base of information on the cells and processes involved in bone maintenance, the most popular hypotheses for how bone cells interact and orchestrate controlled remodeling remain controversial and unverified. In order to leverage the primary literature towards testing the feasibility of two particular hypotheses, I created an agent-based model (ABM) structured on the known locations, properties, and behaviors of osteoclasts, osteocytes, and osteoblasts. Bone's ability …