A systems approach to bone pathophysiology

With evolving interest in multiscalar biological systems one could assume that reductionist approaches may not fully describe biological complexity. Instead, tools such as mathematical modeling, network analysis, and other multiplexed clinical- and research-oriented tests enable rapid analyses of high-throughput data parsed at the genomic, proteomic, metabolomic, and physiomic levels. A physiomic-level approach allows for recursive horizontal and vertical integration of subsystem coupling across and within spatiotemporal scales. Additionally, this methodology recognizes previously ignored subsystems and the strong, nonintuitively obvious and indirect connections among physiological events that potentially account for the uncertainties in medicine. In this review, we flip the reductionist research paradigm and review the concept of systems biology and its applications to bone pathophysiology. Specifically, a bone-centric physiome model is presented that incorporates systemic-level processes with their respective therapeutic implications.