Targeting ferroptosis: A novel therapeutic avenue in osteoarthritis and bone degeneration

Abstract

Osteoarthritis (OA) and bone degeneration are progressive musculoskeletal disorders that compromise joint function, cause chronic pain, and reduce quality of life in aging populations. While current therapeutic approaches aim to manage symptoms, there remains a significant unmet need for disease-modifying treatments. Ferroptosis, a distinct iron-dependent form of regulated cell death  characterized by lipid peroxidation, has emerged as a crucial pathological mechanism in multiple degenerative diseases. Recent advances suggest that ferroptosis contributes to chondrocyte death, subchondral bone remodeling, and the inflammatory milieu observed in OA and other bone degenerative conditions. This review consolidates current knowledge on the molecular mechanisms linking ferroptosis to bone tissue pathology, highlights key regulatory pathways involved, and discusses emerging therapeutic interventions aimed at modulating ferroptotic activity. We also explore the potential of ferroptosis-targeting agents as novel disease-modifying drugs in OA and bone degeneration, and outline future research directions and translational implications.