Low-dose radiotherapy in osteoarthritis: a comprehensive review of immunological and molecular mechanisms

Osteoarthritis (OA) is a disabling joint disease that is often accompanied by progressive cartilage loss and chronic inflammation, commonly causing pain and decreased mobility. While traditional treatments, pain relief through the use of analgesics, corticosteroid injections, and joint replacement, primarily control symptoms, they do not halt disease progression. Low-dose radiotherapy (LDRT) is an emerging non-surgical therapy of immense potential, particularly in patients unresponsive to conventional treatment. This review synthesizes current knowledge of the mechanistic rationale and clinical utility of LDRT as an adjunctive OA treatment.

Recent findings illustrate LDRT's ability to modulate significant immunological and molecular processes involved in OA pathogenesis, such as suppressing pro-inflammatory cytokines (e.g. TNF-α, IL-1β, IL-6), increasing anti-inflammatory mediators (e.g. IL-10, TGF-β), suppressing matrix-degrading enzymes (e.g. MMP-13), and restoring mitochondrial activity through modulation of oxidative stress. Additionally, LDRT influences inflammatory cell activity within the local joint microenvironment without inducing systemic immunosuppression. While available data suggest a favorable safety profile, standardized protocols and long-term outcomes are still lacking, necessitating further high-quality randomized controlled trials.