Low-Dose Radiation Shows Promise for Slowing Knee Osteoarthritis in Long-Term Trial

For millions of people living with knee osteoarthritis, treatment has long meant a choice between managing symptoms and waiting for the joint to wear out. A new long-term analysis of a randomized trial, presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting in Boston, suggests that a therapy usually associated with cancer care may do something standard treatments cannot: slow the structural deterioration of the joint itself. The study followed nearly 300 patients in Russia for almost 12 years and found that those treated with very low doses of radiation experienced sustained relief from pain, better physical function, measurably less joint damage on MRI scans, and, in the most encouraging subgroup, dramatically lower rates of disability and knee replacement surgery.

The trial enrolled 292 patients with symptomatic knee osteoarthritis classified as Kellgren-Lawrence grade 0, 1 or 2 on X-ray, a scale that ranges from no definite visible disease to definite bone spurs with possible early narrowing of the joint space. Notably, even patients with grade 0 X-rays showed evidence of osteoarthritis on MRI, meaning the study captured disease at its earliest stages. Patients with advanced grade 3 and 4 disease were excluded, keeping the focus squarely on early to moderate disease. The participants were unusually young for an osteoarthritis study, with a median age of just 38 years, a detail that makes the long follow-up period particularly valuable for tracking how the disease evolves over decades of life.

Participants were randomly assigned at a single institution in Russia to one of two treatment arms. The control group received glucosamine and chondroitin, two widely used dietary supplements often prescribed for joint health. The experimental group received the same medications plus a course of low-dose radiation therapy totaling 4.5 Gray, delivered in 10 treatments using an orthovoltage machine that generates low-energy X-rays. That total dose is a small fraction of what is used to treat cancer, where curative regimens often exceed 40 to 60 Gray. The rationale for using radiation at such low doses rests on a well-documented biological phenomenon: while high doses kill cells, very low doses can suppress inflammatory signaling, modulating the chronic inflammation that drives cartilage breakdown in osteoarthritis.

The short-term results reinforced what earlier studies had suggested. Both groups reported less pain immediately after treatment, but only the radiation arm sustained that benefit over time. Patients who received radiation therapy also reported significantly greater and more durable improvements in physical function and quality of life than those treated with medication alone. Because osteoarthritis has no cure and conventional therapies such as exercise, weight management, medications and injections relieve symptoms without reliably slowing structural progression, a treatment that could alter the disease course would represent a genuine shift in the field.

The structural evidence came from MRI scans tracked for three years after treatment. At 12 months, imaging scores showed slight improvement among patients who received radiation therapy, while the medication-only group continued to worsen. The significant difference between the groups persisted throughout the follow-up period. This alignment between what patients felt and what the scanner saw is what makes the study stand out, according to study author Bobby (Nagendra) Koneru, MD, FASTRO, a radiation oncologist at Loyola University in Maywood, Illinois. In his view, the most compelling aspect is how the outcomes fit together: sustained improvement in pain and function, less joint deterioration on MRI, and years later, less disability and fewer knee replacements among patients with grade 2 disease.

The long-term outcomes came from regional health records examined over a median follow-up of 11.9 years. Across the entire study population, radiation therapy was associated with a statistically significant 67 percent lower adjusted hazard of government-certified disability due to knee osteoarthritis. Koneru emphasized that this endpoint reflects an independently certified consequence of knee disease rather than a subjective report, complementing the improvements seen in symptoms and imaging. Because disability certification in the Russian system involves an external government assessment, the finding is less vulnerable to the placebo effects that can inflate patient-reported outcomes in unblinded trials.

The most striking results emerged among the 78 patients with grade 2 disease, where osteoarthritis was established but not yet advanced. Disability developed in 31 percent of patients who received radiation therapy compared with 61 percent of those on medication alone, and knee replacement was performed in 14 percent versus 36 percent respectively. Both differences were statistically significant. Koneru suggested that grade 2 disease may represent a window in which osteoarthritis is present but extensive joint damage has not yet occurred, offering an opportunity to study whether treating inflammation earlier can change the longer course of the disease. Across the full study population, however, the difference in knee replacement rates did not reach statistical significance, a caveat the researchers acknowledged.

The study carries important limitations that temper enthusiasm. Participants knew whether they had received radiation, and the control group received medication rather than simulated radiation, leaving open the possibility that expectation effects contributed to the symptom improvements. The long-term outcomes and the grade 2 subgroup analyses were exploratory rather than pre-specified primary endpoints. Follow-up MRI data were incomplete, although the imaging readers were blinded to treatment assignment. The trial was also conducted at a single institution in Russia, and differences in health care delivery or access to knee replacement may limit how broadly the results apply to other populations and health systems.

Safety data were reassuring within the limits of the study design. No acute radiation reactions or cancers within the treated area were reported during follow-up. Low-dose radiation therapy has been used for decades in parts of Europe and increasingly in the United States to relieve pain from osteoarthritis and other noncancerous inflammatory conditions. Still, the study was not designed to quantify rare late effects or lifetime cancer risk, a particularly relevant question in a population with a median age of 38, and larger prospective studies will be needed to assess long-term safety alongside the durability of benefit.

Experts outside the study team see the findings as a reason to push the science forward rather than a reason to change practice immediately. Gopal K. Bajaj, MD, MBA, FASTRO, co-chair of ASTRO’s Functional Radiation Medicine Task Force and a radiation oncologist at Inova Schar Cancer Institute in Fairfax, Virginia, noted that osteoarthritis treatments can help patients feel better but that there is far less evidence they change what is happening inside the joint. What makes these findings interesting, he said, is that the patient-reported improvement was accompanied by a measurable difference on MRI, moving the question beyond pain relief alone, and the long-term disability data add another reason to test whether low-dose radiation can affect the course of early osteoarthritis in a larger, rigorously controlled trial. Koneru agreed, calling for a multicenter randomized trial using simulated radiation as the control, with prospectively defined imaging and long-term clinical endpoints and a focus on patients with grade 2 disease. If such a trial confirms these results, a therapy borrowed from the cancer clinic could become a disease-modifying option for one of the world’s most common causes of chronic pain and disability.

Subject of Research: Low-dose radiation therapy for knee osteoarthritis progression

Article Title: Low-dose radiation therapy may slow progression of knee osteoarthritis, long-term study indicates

Article References: Low-dose radiation therapy may slow progression of knee osteoarthritis, long-term study indicates. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: low-dose radiation therapy, knee osteoarthritis, randomized trial, cartilage deterioration, MRI imaging, disability prevention, knee replacement, inflammation, orthovoltage X-rays, ASTRO, Kellgren-Lawrence grade, disease-modifying treatment