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Coupling microporomechanics and multiscale systems biology for computer simulation-based prediction of bone remodeling

Bone remodeling is the mechanically and biochemically modulated process enabling the continuous renewal of the hierarchically composed material “bone”, which is key for maintaining its mechanical integrity, as well as for the adaption of the bone composition in response to a changing physical activity. Remarkably, many of the processes together referred to as “bone remodeling” are characterized by significant length scale transitions. For example, while mechanical loading acts onto the body macroscopically, the single components of bone are mechanically stressed based on the macroscopic loading, but also on their respective component stiffnesses, their volume fractions, and interactions with other components. Osteocytes, i.e. cells residing in the roughly 10 microns-sized lacunar pore space, sense local changes of the mechanical loading, and translate these changes into corresponding biochemical factors. In turn, these factors are perceived by the bone-building osteoblasts and bone-resorbing osteoclasts, both located in the 50 to 100 microns-sized vascular pore space. The interplay of osteoblasts and osteoclasts governs then the development of the bone composition, which determines how the macroscopic mechanical loading arrives locally; and so on and so forth.
Here a mathematical modeling strategy is presented, by means of which the progress of the bone remodeling-governing processes can be adequately predicted, namely on the correct length scales. In more detail, a microporomechanical model is utilized for estimating the cell activity-modulating local mechanical stimuli, in particular the hydrostatic pressure to which osteocytes are subjected. This model is coupled to a multiscale systems biology model, involving the activities and effects of the dominant biochemical factors and the bone cells, derived based on formulation of conservation laws, and on the principle of mass action kinetics. Finally, the model is applied for studying the development of the bone composition in the course of progressing osteoporosis, as well as of mechanical disuse and overuse.

Author(s):

Stefan Scheiner    
Vienna University of Technology
Austria

Maria Pastrama    
Vienna University of Technology
Austria

Peter Pivonka    
The University of Melbourne
Australia

Christian Hellmich    
Vienna University of Technology
Austria