Osteoarthritis (OA) is the most common form of arthritis. It is characterized by progressive destruction of articular cartilage and the development of chronic pain and constitutes a considerable socioeconomic burden. Currently, pharmacological treatments mostly aim to relieve the OA symptoms associated with inflammation and pain. However, with increasing understanding of OA pathology, several potential therapeutic targets have been identified, enabling the development of disease-modifying OA drugs (DMOADs). By targeting inflammatory cytokines, matrix-degrading enzymes, the Wnt pathway, and OA-associated pain, DMOADs successfully modulate the degenerative changes in osteoarthritic cartilage. Moreover, regenerative approaches aim to counterbalance the loss of cartilage matrix by stimulating chondrogenesis in endogenous stem cells and matrix anabolism in chondrocytes. Emerging strategies include the development of senolytic drugs or RNA therapeutics to eliminate the cellular or molecular sources of factors driving OA. This review describes the current developmental status of DMOADs and the corresponding results from preclinical and clinical trials and discusses the potential of emerging therapeutic approaches to treat OA.

Osteoarthritis is a significant global health problem. Many patients seek more effective alternatives to nonsteroidal anti-inflammatory medicines or commercial supplements to manage joint pain and inflammation. FlexPro MD^® (FP-MD) combines krill oil, astaxanthin, and lower molecular weight hyaluronic acid to support joint health. A 12-week, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of FP-MD and placebo once daily in participants (n = 100) with mild osteoarthritis of the knee or hip joint. For the primary endpoint of joint pain score, per-protocol participants (n = 75) in the FP-MD group (n = 37) had a statistically significantly greater mean reduction from baseline in the Korean Visual Analog Scale (K-VAS) at week 12 compared with participants in the placebo group (n = 38) (20.8 ± 16.16 mm vs. 10.6 ± 17.58, p = 0.0105). The Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC) total score was also significantly improved in the FP-MD group at week 12 compared with placebo (−13.0 ± 13.62 vs. −5.5 ± 18.08, p = 0.0489), especially an improvement in pain score (−2.5 ± 2.92 vs. −1.3 ± 3.94, p = 0.02635). FP-MD group had greater improvement in joint function scoring by investigator assessment (p = 0.0127) and by group participants (p = 0.0070). A statistically significantly greater number of patients reported adverse events in the placebo group compared with the FP-MD group (16% vs. 4%, p = 0.0455), most commonly gastrointestinal disorders in both of the groups. These findings suggest that FP-MD is well tolerated and can be effectively used to address joint pain in patients diagnosed with mild osteoarthritis, the main symptom of this condition.