A single course of low-dose radiation therapy has demonstrated significant pain relief and functional improvement in patients with knee osteoarthritis, according to results from a randomized, placebo-controlled clinical trial presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting. The study, led by Seoul National University College of Medicine, offers new hope for the estimated 32.5 million U.S. adults living with osteoarthritis.
Trial Design and Patient Population
The multicenter trial enrolled 114 patients with moderate-to-mild knee osteoarthritis across three academic centers in Korea. Participants were diagnosed based on moderate damage visible on X-rays and significant pain with walking. They were randomly assigned to one of three groups: very low-dose radiation (0.3 Gy total over six sessions), low-dose radiation (3 Gy total over six sessions), or a sham treatment that simulated radiation therapy without delivering any actual radiation.
"People with painful knee osteoarthritis often face a difficult choice between the risks of side effects from pain medications and the risks of joint replacement surgery," said Byoung Hyuck Kim, MD, PhD, the trial's principal investigator and assistant professor of radiation oncology at Seoul Metropolitan Government-Seoul National University Boramae Medical Center. "There's a clinical need for moderate interventions between weak pain medications and aggressive surgery, and we think radiation may be a suitable option for those patients, especially when drugs and injections are poorly tolerated."
Radiation Dosing and Safety Profile
The radiation doses used in the study were substantially lower than those employed in cancer treatment. Each treatment session delivered 500 milligray (mGy), equivalent to approximately 5,000 times the radiation dose of a chest X-ray and around 70 times that of a chest CT scan. However, the total 3 Gy dose represents less than 5% of the 50-70 Gy typically used in cancer radiotherapy.
"There is a misconception that medicinal, or therapeutic, radiation is always delivered in high doses," Kim explained. "But for osteoarthritis, the doses are only a small fraction of what we use for cancer, and the treatment targets joints that are positioned away from vital organs, which lowers the likelihood of side effects."
Clinical Outcomes and Efficacy
To ensure accurate assessment of treatment effects, participants were restricted from taking regular pain medications during the first four months, with only acetaminophen allowed as needed. Response to treatment was measured using internationally accepted criteria that classify patients as "responders" if they achieve meaningful improvement in at least two of three areas: pain, physical function, and overall assessment of their condition.
After four months, 70% of patients in the 3 Gy group met responder criteria, compared to 42% in the placebo group (p=0.014). The very low-dose 0.3 Gy group showed 58% improvement, which was not statistically significant compared to the control group (p=0.157).
Meaningful improvements in the composite score of pain, stiffness, and physical function were reported more frequently in the 3 Gy group (57%) compared to the placebo group (31%, p=0.024). No treatment-related side effects or toxicity were reported throughout the study period.
Distinguishing Treatment Effects from Placebo Response
The study's design addressed a critical challenge in osteoarthritis research by including a true placebo control group. "The sham-controlled design helped rule out placebo effects, and we limited stronger analgesics, which made differences between groups more clearly attributable to the radiation itself," Kim noted.
The substantial placebo response rate of approximately 40% was consistent with rates reported in prior osteoarthritis trials involving injections or medications. "It was surprising, and it underscores how important placebo-controlled designs are in osteoarthritis research," Kim observed.
Patient Selection and Treatment Limitations
The researchers emphasized that radiation therapy may be most effective for patients with underlying inflammation and preserved joint structure. "For severe osteoarthritis, where the joint is physically destroyed and cartilage is already gone, radiation will not regenerate tissue," Kim explained. "But for people with mild to moderate disease, this approach could delay the need for joint replacement."
Kim stressed that low-dose radiation should be considered as part of shared decision-making alongside standard measures such as weight loss, physiotherapy, and medications. "In clinical practice, responses could be even stronger when radiation is properly combined with other treatments, and patient satisfaction may be higher than with current options alone."
Future Research Directions
The research team is conducting 12-month follow-up assessments to evaluate the durability of treatment benefits and correlate symptom relief with imaging-based measures of joint structure. Planned studies include larger, pragmatic trials to evaluate outcomes in specific patient subgroups and health-economic analyses comparing low-dose radiation with injections and medication regimens.
While low-dose radiation therapy for joint pain is regularly used in European countries such as Germany and Spain, awareness remains limited among healthcare professionals in other countries. The positive results from this placebo-controlled trial may help establish the treatment as a viable option for patients seeking alternatives to conventional pain management approaches or surgical intervention.
