Molecular hydrogen and osteoarthritis: multi-target mechanisms and therapeutic effectiveness

Osteoarthritis is a prevalent degenerative joint disease characterized by a self-perpetuating cycle of chronic inflammation, oxidative stress, and extracellular matrix degradation. Current therapies provide only symptomatic relief and do not alter disease progression, highlighting the urgent need for effective disease-modifying osteoarthritis drugs. Molecular hydrogen has emerged as a promising therapeutic candidate due to its unique selective antioxidant, anti-inflammatory, and anti-apoptotic properties. This review summarizes the multi-target mechanisms of molecular hydrogen and highlights innovative delivery technologies designed to overcome its key pharmacokinetic limitations, especially rapid diffusion and short residence time in the joint. We critically evaluate advanced strategies ranging from sustained-release injectable depots to stimulus-responsive nanocarriers and cell-based delivery systems. Clinical translation remains at an early stage; progress will depend on integrating intelligent, localized delivery systems with rigorously designed clinical trials to validate molecular hydrogen as a safe and effective disease-modifying osteoarthritis drug.