Balneotherapy in knee osteoarthritis: a review of therapeutic efficacy and inflammatory cytokine regulation

Abstract Knee osteoarthritis (KOA) is a common degenerative joint disease with an inflammatory component. Balneotherapy has been used for KOA, but its clinical efficacy and mechanisms remain uncertain. This narrative review summarizes clinical evidence and proposes a hypothesis-generating mechanistic framework. PubMed and CNKI were searched up to June 2026. Interventions were categorized as mineral-water bathing, aquatic exercise/hydrotherapy, mud therapy/pelotherapy, or multimodal spa programmes, and clinical studies were assessed for risk of bias. Randomized trials and meta-analyses suggest that balneotherapy may improve short-term pain and function, with benefits reportedly persisting for 3–9 months in some studies; however, most trials had high risk of bias, heterogeneous protocols, small samples, and short follow-up. Mechanistic evidence is largely preclinical or indirect. H₂S has the most consistent anti-inflammatory and anti-catabolic rationale, acting via NF-κB and MMP-13 inhibition. Calcium and magnesium may modulate TRPV4/NLRP3 and NF-κB signaling, but human balneotherapy evidence is lacking, and mineral synergy remains unverified. A three-tier “heat–mineral–signal” framework is proposed, but target engagement after bathing and causality between biomarker changes and clinical improvement have not been established. Overall, balneotherapy may offer symptomatic benefits in KOA, but current evidence is limited and heterogeneous. The proposed mechanistic model is hypothesis-generating; higher-quality trials with standardized protocols, long-term follow-up, and integrated clinical and mechanistic outcomes are needed.