Osteoarthritis is considered an incurable disease as, to date, there has been no way to halt or reverse the pathological changes and effecting a ‘cure’. Most management efforts are focused on alleviating pain or symptoms of the disease. The ideal management method would do both – alleviate symptoms but also modify the disease process, slowing pathological changes and promoting tissue repair or regeneration. The disconnect between the pain a patient shows, and the pathology present must be noted here. Also note that most patients have advanced intra-articular pathology when they begin to show clinical signs.
We still do not fully understand exactly why a joint starts to develop OA or exactly where the process starts. Is it in articular cartilage? The subchondral bone? The synovium? We still do not fully understand the full pathophysiological changes that drive the disease, but we do know that it is characterised by chronic low-grade inflammation and that that is likely due to an imbalance of pro-and anti-inflammatory signalling involving various cytokines and other biochemical factors.
This is where pathophysiology becomes important as certain of these cytokines have become specific targets for precision medicine to manage OA. Traditionally anti-inflammatory agents such as corticosteroids and Non-Steroidal Anti-inflammatory Agents (NSAIDs) have been used successfully to manage inflammation and pain by targeting Prostaglandin -E. Novel treatments are being developed targeting other pro-inflammatory agents such as Interleukin-1 (IL-1), Interleukin -6 (IL-6) and Tumour Necrosis Factor (TNF-alpha). New targets for treatment have been identified such as Nerve Growth Factor (NGF) and treatments using anti -NGF mAbs have produced significant symptomatic benefits and are currently used widely in general practice.
Biological techniques utilising mesenchymal stem cells (MSC) or potentiated platelet preparations (PRP) also act to influence the innate immune system within the synovium by delivering packets of growth factors into the joint. These influence the cell population within the joint to retore an anabolic, anti-inflammatory environment to exact their effect.
Techniques are also being developed to harness the advantages of MSCs in a more controlled fashion and deliver long-acting modification solutions to counter the chronic long-acting pathophysiological actions in the disease 1 .
The exciting promise of these new immunotherapy techniques is that they may be able to alter the pathological change within the joint and effectively modify the disease. It is early days, but this is a glimmer of hope that we may have much more control over the disease by controlling the early pathophysiological changes.
We must understand however that this is much more likely in the very early disease before we have advanced pathology with the involvement of all the structures we have highlighted earlier in this Module.
References
- Drohat P et al (2025) Long-Acting Extracellular Vesicle-Based Biologics in Osteoarthritis Immunotherapy. Bioengineering 2025, 12, 525. https://doi.org/10.3390/bioengineering12050525