A Lattice-Based Computational Model of Microscopic Bone Resorption In Cortical Bone Multicellular Units

Bone resorption by osteoclasts is an essential phase in the bone remodelling cycle as it creates the physiological conditions for subsequent bone formation. While several properties of osteoclastic bone resorption in cortical Bone Multicellular Units (BMU) have been assessed experimentally, the precise spatio-temporal dynamics, movement pattern, apoptotic state (single nuclei vs. whole cell) of the osteoclasts remain to be elucidated. Furthermore, the individual effects that these behaviours confer on the shape and extent of the resorption cavity are unclear. In this work, we develop a lattice-based computational model focused on bone resorption in cortical BMUs to address these questions. Our model takes into account the interaction of osteoclasts with the bone matrix, the interaction of osteoclasts with each other, the production of osteoclasts from the tip of a growing blood vessel, apoptosis time of osteoclasts, and the renewal of osteoclasts’ nuclei by cell fusion. All these features are shown to strongly affect the geometrical properties of the developing resorption cavity including shape, size, and progression rate, but also the resorption pattern, lifespan and average resorption rate of individual osteoclasts, as well as their spatial distribution in the BMU. In particular, our numerical simulation results indicate that the growth of a blood vessel and the continual renewal of the osteoclasts’ nuclei are essential physiological features for functional resorption by cortical BMUs, without which balanced bone renewal may be compromised.