A mechano-chemo-biological model for bone remodeling with a new mechano-chemo-transduction approach

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ORIGINAL PAPER

A mechano‑chemo‑biological model for bone remodeling with a new mechano‑chemo‑transduction approach Mehran Ashrafi1 · José Eduardo Gubaua2 · Jucélio Tomás Pereira2 · Farzan Gahlichi1 · Manuel Doblaré3,4,5  Received: 4 December 2019 / Accepted: 29 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Bone remodeling is a fundamental biological process that develops in bone tissue along its whole lifetime. It refers to a continuous bone transformation with new bone formation and old bone resorption that changes the internal microstructure and composition of the tissue. The main objectives of bone remodeling are: repair of the internal microcracks; adaptation of the macroscopic stiffness and strength to the actual changing mechanical demands; and control of the calcium homeostasis. Understanding this process and predicting its evolution is critical to reduce the effects of long-term disuse as happens during periods of reduced mobility. It is also important in the design of bone implants to avoid long-term stress shielding. Many mathematical models have been proposed from the earliest purely phenomenological to the latest that include biological knowledge. However, there still exists a lack of connection between the mechanical driving force and the biochemical and cell processes it triggers. Here, and following previous works that model independently the mechanobiological and biochemical processes in bone remodeling, we present a more complete model, useful for both cortical and trabecular bone, that uses a new mechanotransduction approach based on the effect of strains onto the bonding–unbonding rate of RANK/RANKL/OPG receptor–ligand reactions. We compare the results of this model with previous ones, showing a good agreement in similar conditions. We also apply it to realistic situations such as a femoral bone after implantation of a hip prosthesis, getting similar results to the clinical ones in the final bone density distribution. Finally, we extend this approach to the anisotropic case, getting not only the mean density, but also the directional homogenization of the microstructure. This biochemical approach permits, not only to predict the bone evolution under changes in the mechanical loads, but also, to consider anabolic and catabolic drugs to control bone density, such as those used in osteoporosis. Keywords  Bone remodeling · Mechano-chemo-biological model · Finite elements · Sensitivity analysis · Hip prosthesis

* Manuel Doblaré [email protected]

2



Federal University of Paraná, UFPR Polytechnic Center, Curitiba, Brazil

Mehran Ashrafi [email protected]

3



Aragón Institute of Engineering Research (I3A), University of Zaragoza, Mariano Esquillor s/n, 50018 Zaragoza, Spain

José Eduardo Gubaua [email protected]

4



Aragón Institute of Health Research (IIS-Aragón), Zaragoza, Spain

Jucélio Tomás Pereira [email protected]

5



Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Avda. de Monfor