Target the Knee as a Whole: Multimodal Approach to Injections in Osteoarthritis
To date, there is no proven effective pharmacological treatment to initiate regeneration of joint tissues, and thus to change the course of the disease. Nevertheless, promising therapeutic modalities have been developed in recent years including mesenchymal stem cells (MSCs) and scaffolds, treatment with small molecules, and gene therapy.
Changing the course of KOA, however, may necessitate a multimodal approach towards the knee joint including a combination of intra-articular with interventions on modifiable risk factors. Importantly, our understanding of OA has evolved redefining the concept of the disease, being in interaction with the human body as a whole. Any future conservative disease-modifying treatment of KOA should aim at a multimodal, holistic approach towards the knee joint including but not limited only to intra-articular injections. A combination with other interventions should be further researched. A recent review by Georgiev et al considers the combination of intra-articular injections with other modalities in the treatment of osteoarthritis of the knee.
The increasing incidence of KOA in the population necessitates immediate measures to bring about a change in the status quo and to achieve the much-needed catharsis in the theory and practice of diagnosing and treating this socially significant disease. Thanks to the recent advances in understanding the nature of the disease and multifactor mechanisms for its origin and development, the first steps have already been taken in the right direction. The new concept of OA as a whole joint disease is crucial to the development of new, targeted therapeutic interventions. Targeting the joint from inside, intra-articular injections for delivery of drugs and macromolecules is a reasonable treatment approach. However, the almost 30-year-old experience with hyaluronic acid-based viscosupplements did not meet the initial expectation of a revolution in the therapy of KOA.
The use of hyaluronans has been seriously criticized for its relative invasiveness, its short period of effectiveness, and its limited impact on joint structures. Intra-articular delivery of novel biologics presents a new alternative for the treatment of KOA. According to EMA, a biological medicinal product (‘biological’) is a medicinal product that contains an active substance that is produced by or extracted from a biological source. In this broad sense, injectable biologics may include stem cells, ortho-biologics, gene therapy, and classical biological disease-modifying antirheumatic drugs (bDMARDs).
In their review, Georgiev et al have stated that: 1) MSCs can lead to favorable clinical results when injected at optimal concentration; 2) scaffolds have the potential to restore osteochondral defects and at least partially affect altered homeostasis of the osteoarthritic knee; 3) inhibition of different signal pathways from small molecules may have an anti-inflammatory and chondroprotective effect; 4) genetic reprogramming of chondrocytes or synoviocytes or the implantation of cells with a new functional role may be the key to non-invasive and long-lasting management of inflammatory and degenerative processes of osteoarthritis. In addition to the many unresolved issues, the sole use of injectable drug delivery may not lead to the desired revolution in the treatment of KOA. Joint injections could not possibly target the variety of pathological changes inherent to the disease process. Their most efficient implementation in the routine clinical practice can be only achieved in multimodal, holistic treatment programs including other comprehensive interventions to ensure joint management as a whole.