Iron as a Key Mediator of Chronic Joint Damage: Insights from Hemophilic Arthropathy and Implications for Osteoarthritis

Background and Objectives: Osteoarthritis (OA) is the most common degenerative joint disease and a leading cause of pain and disability worldwide. Increasing evidence indicates that dysregulated iron metabolism contributes to joint degeneration by promoting inflammation, oxidative stress, and cartilage damage. Hemophilic arthropathy (HA), a severe complication of hemophilia caused by recurrent hemarthroses, represents a unique model of iron-driven joint degeneration. This narrative review summarizes current evidence on the contribution of iron deposition to the pathogenesis of hemophilic arthropathy and discusses its relevance to knee osteoarthritis (KOA). Materials and Methods: The literature was reviewed using the PubMed, Scopus, and Web of Science databases, focusing on published studies addressing iron deposition, synovial inflammation, angiogenesis, oxidative stress, cartilage degeneration, subchondral bone remodeling, and dysregulated iron metabolism. Results: Current evidence indicates that iron stored primarily as hemosiderin promotes persistent synovial inflammation and progressive joint destruction. Several pathological pathways associated with iron accumulation, including chronic low-grade inflammation, extracellular matrix degradation, and altered bone remodeling, are shared by HA and KOA. Conclusions: These findings suggest that iron-mediated mechanisms may provide important insights into OA pathogenesis and support further investigation of iron as a potential diagnostic and therapeutic target in degenerative joint diseases.