Modeling treatment of osteoarthritis with standard therapy and senolytic drugs

by Nourridine Siewe, Avner Friedman

Osteoarthritis (OA), the most common form of joint disease, involves the progressive degradation of articular cartilage and is a major cause of chronic disability in aging populations. Since OA is associated with severe deficiency of collagen type II, clinical trials considered treatment of OA by injection with undenatured collagen type II (UC-II). Recent studies consider also injection of senolytic drugs, like fisetin, that eliminates senescent chondrocytes in aging patients, to reduce the negative effect of these senescent cells on cartilage structure. In this paper we develop a mathematical model of OA for men and, separately, for women, and use the model to assess the efficacy of treatment by UC-II and by fisetin, alone or in combination. Our computations show the benefits of starting treatment early. They also show that although the effect of treatment by fisetin on slowing the progression of OA is much smaller compared to UC-II treatment, its effect in combination with UC-II is significantly increased.