Predictive, multi-scale, multi-factorial Mathematical modeling of Knee OsteoArthritis

Osteoarthritis (OA) is one of the leading causes of disability worldwide with pain and reduced function as hallmark symptoms. OA can currently not be cured, and the available treatments are focused on improving symptoms. OA is a multi-scale and multi-factorial degenerative joint disease with knee OA (KOA) being the most frequent. Biomechanical factors play an important role in maintaining joint homeostasis and several early KOA interventions are aimed at altering the bodylevel biomechanics to reduce joint degeneration that occurs largely due to changes at the cell level. However, the relationship between levels, i.e. body, joint, tissue and cell, and its relationship to pain response, is currently poorly understood.

To tackle this challenge, we are bringing together mathematical modeling experts whose combined expertise cover multi-scale modelling, including mechanobiology and experimental tissue characterization of bone, cartilage and tendons with the world's leading scientist in pain mechanisms in KOA to establish the first comprehensive predictive model of KOA, capturing also the interaction between loading and pain. In addition to a fundamental understanding, the mathematical model also enables personalization of the treatments based on prediction of expected outcome.

Initially, we will develop clinically feasible measurement techniques to obtain model inputs. Hereafter, mathematical models of the body, joint, tissue and cell levels are researched and coupled to a model of the pain response to enable investigations of the relationship between KOA interventions and the multi-scale response. Validation activities are conducted to evaluate the accuracy of the sub-level models as well as the predictive capabilities of the multi-scale model in a cohort study initiated during the project. Finally, the predictive capabilities of the model are applied to design novel, personalized KOA interventions with the ultimate goal to improve patient care.

Mathematical Modeling, Knee, Osteoarthritis, Multi-scale