Low-Dose Radiation Therapy for Osteoarthritis: A Critical Review and Proposal for Integration Into Contemporary Care

Osteoarthritis (OA) is a leading cause of pain and disability and continues to grow as a global health burden, yet many patients remain symptomatic despite guideline-directed pharmacologic, injectable, and surgical treatments. Low-dose radiation therapy (LDRT) has long been used in parts of Europe for benign painful joint disease and is now re-emerging as a noninvasive option for OA, although it remains underutilized and somewhat controversial in the United States. In this critical review, we synthesize mechanistic, clinical, and safety data for LDRT in OA, appraise standard therapies and key randomized controlled trials (RCTs) of LDRT, and position LDRT within a multidisciplinary care pathway. Preclinical and translational studies indicate that doses of 0.3-0.7 gray (Gy) per fraction (3-6 Gy total) reduce proinflammatory cytokine expression, blunt leukocyte-endothelial adhesion, and shift macrophages toward an anti-inflammatory phenotype, with concordant systemic immune changes documented in the immune modulation by low-dose radiation therapy (IMMO-LDRT01) cohort. Large European observational series report 60-80% pain response with minimal acute toxicity and a very low absolute rate of in-field second malignancy (three events, 0.064%, in a 4,699-patient orthovoltage cohort followed for a median of more than a decade) but are vulnerable to placebo effects and regression to the mean. Early sham-controlled RCTs were neutral, yet more recent randomized trials, including a double-blind sham-controlled study from Iran, the Korean low-dose radiation therapy for patients with knee osteoarthritis (LoRD-KNeA) trial, and a Russian RCT with a nine-year follow-up, demonstrate clinically meaningful improvements in pain and function and a possible reduction in arthroplasty and disability. Pooling the three sham-controlled trials that report an estimable between-group effect on pain yields a standardized mean difference of -0.19 (95% CI -0.72 to +0.33) with substantial heterogeneity (I² = 66%), indicating that the randomized signal is dose- and population-dependent rather than uniformly positive. We conclude that LDRT, prescribed as 3 Gy in six 0.5 Gy fractions, is a reasonable non-surgical option to offer selected patients aged ≥50 years with refractory OA as a second- or third-line option, provided outcomes are captured prospectively.