Towards a virtual bone lab: multiscale interplay between architecture, complexity, and dynamics*

Trabecular bone is a flexible, lightweight tissue that exhibits hierarchical mechanisms of fracture resistance across scales. At the mesoscale, it resembles a web of interconnected struts (trabeculae) that erode with age and diseases such as osteoporosis, resulting in increased fracture propensity. Recent ex vivo experiments have indicated that the traditional macroscale diagnostic marker of osteoporosis, bone mineral density (BMD), correlates poorly with bone strength when used as a sole predictor, but that it can explain much of the variation in bone strength when considered in conjunction with architectural features. We introduce a novel approach to modeling trabecular bone that combines network analysis with simulations of mechanical loading and failure, enabling a unique characterization of how bone architecture contributes to robustness and resilience. We generate network models from tomographic images of real human vertebral bone. Weighted edges represent trabeculae and nodes represent branch points where trabeculae meet. We simulate loading and deformation on finite element models in which edges are replaced by beams, resulting in a considerable reduction in computation time in comparison with fine- grained models used for in silico validation. The beam-element analysis facilitates direct comparison of mechanics and topology at multiple scales ranging from that of individual edges (beams) to the network as a whole. In addition, we discuss implications of our work in the context of clinical application, facilitated by advances in data acquisition methods for assessing fine tissue structure, and we highlight future directions for integrating our results into a comprehensive characterization of bone that links its molecular constituents at the nanoscale to its architecture at large.