From Pathogenesis to Therapy in Knee Osteoarthritis: Bench-to-Bedside

Abstract

Osteoarthritis (OA) is currently the most widespread musculoskeletal condition and primarily affects weight-bearing joints such as the knees and hips. Importantly, knee OA remains a multifactorial whole-joint disease, the appearance and progression of which involves the alteration of articular cartilage as well as the synovium, subchondral bone, ligaments, and muscles through intricate pathomechanisms. Whereas it was initially depicted as a predominantly aging-related and mechanically driven condition given its clear association with old age, high body mass index (BMI), and joint malalignment, more recent research identified and described a plethora of further factors contributing to knee OA pathogenesis. However, the pathogenic intricacies between the molecular pathways involved in OA prompted the study of certain drugs for more than one therapeutic target (amelioration of cartilage and bone changes, and synovial inflammation). Most clinical studies regarding knee OA focus mainly on improvement in pain and joint function and thus do not provide sufficient evidence on the possible disease-modifying properties of the tested drugs. Currently, there is an unmet need for further research regarding OA pathogenesis as well as the introduction and exhaustive testing of potential disease-modifying pharmacotherapies in order to structure an effective treatment plan for these patients.

Keywords: bone remodeling; cartilage; disease modifying drugs; hyaluronic acid; inflammation; knee joint; mesenchymal stem cells; osteoarthritis; ozone; platelet-rich plasma.

Figure 1

Therapeutic interventions targeting cartilage breakdown, bone remodeling, and inflammation in knee osteoarthritis (OA).

Figure 2

Therapeutic options targeting cartilage damage in knee OA.

Figure 3

The main structural changes in the subchondral bone occurs in OA depending on the stage of the disease (early or late). In the early stage, there is an increase in subchondral bone turnover characterized by thinning of the subchondral bone plate and by increasing porosity associated with impairment of the trabeculae: thickness decreasing and separation increasing. The late stage of OA is characterized by thickening of the plate and trabecular layers, by decreasing bone marrow spacing, by sclerosis of the subchondral bone, and by decreased mineralization.

Figure 4

Therapeutic options targeting subchondral bone remodeling for knee OA.

Figure 5

Drugs, dietary supplements, and other interventions contributing to a reduction in inflammation in knee OA.