Objective: The purpose of this study is to assess novel pharmacotherapies for osteoarthritis (OA) that attempt to slow disease progression and improve patient outcomes by targeting fundamental pathophysiological pathways, rather than simply relieving symptoms.

Methods: This review used PRISMA criteria to collect studies. The study included peer-reviewed articles, clinical trials, meta-analyses, and systematic reviews published between 2000 and 2023 on both traditional and innovative treatments for OA. A comprehensive PubMed search yielded publications employing keywords linked to specific OA pharmacotherapies, resulting in 76 eligible studies once exclusion criteria were applied.

Results: Conventional medications for pain management, such as NSAIDs, paracetamol, and corticosteroids, continue to be helpful, but they have severe adverse effects. Novel pharmacotherapies provide promise for disease modulation. Fibroblast growth factor 18 (FGF-18) and Wnt pathway modulators such as lorecivivint show promise in cartilage regeneration and joint health. Matrix extracellular phosphoglycoprotein (MEPE)-derived peptides and matrix metalloproteinase (MMP) inhibitors, notably selective MMP-13 inhibitors, target cartilage breakdown mechanisms and have demonstrated promising preclinical results. RNA-based treatments and aggrecanase inhibitors have also shown promise in decreasing OA progression, however clinical validation is still awaited.

Conclusion: While traditional treatments are important for symptom alleviation, new pharmacotherapies offer exciting opportunities for disease modification in OA. Continued clinical trials are required to ensure efficacy and safety. Integrating these innovative techniques with standard medicines and personalised care has the potential to transform OA therapy and improve long-term patient outcomes.