3D model of bone remodeling coupled with a drug effect

Total hip replacement, which is a successful solution for restoring movement to damaged joints, becomes nowadays a common surgical procedure. However the lifespan of hip implants is limited, because of pathologic strain distribution in bone inducing bone-resorption and limiting the long-term stability of implant in bone. Currently research is being done to enhance the lifespan of these implants by their use as drug delivery system. However, a real need of understanding how the used drug behaves and affects bone remodeling still remains. Mathematical modeling and numerical simulations of the drug effect coupled with bone remodeling help in reducing and orienting animal experimentations needed for the development of drug delivery implants. In this project, a numerical model, that includes bone remodeling due to mechanical loadings extended with a drug effect, was implemented in Abaqus finite element program. The drug effect encompassed the drug diffusion and a supplemental stimulus that is function of drug concentration. After implementation, the model was applied to an in vivo study in order to validate its predictability of bone density evolution due to zoledronate, which was locally delivered in rat tibias by PLA-coated implants. The numerical results obtained open the doors to new perspectives. Indeed, the implementation of the remodeling and the diffusion of the drug were successfully achieved and reveal a large precision, less than 1% error between analytical solutions and model predictions. Nevertheless, the experimental validation of the drug effect has revealed that zoledronate is not the most suitable drug, to which the model could be applied. Besides, some key parameters of the model must be determined in order to give the best model-predictions of bone density. The key parameters of the model that have been identified in this project are: rate of drug release, drug diffusivity and the interpolated function of drug stimulus. The model developed in this project may be an interesting tool for determining optimal considerations of a drug delivery device