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

Low-dose radiation therapy may do more than relieve pain from early knee osteoarthritis, with a long-term analysis suggesting it could also influence how the disease progresses. The findings come from a new analysis of a randomized trial conducted in Russia that followed nearly 300 patients for almost 12 years.

Patients who received low-dose radiation therapy had more sustained improvements in pain, physical function and quality of life than those who received medication alone, and MRI scans showed significantly less structural deterioration inside the knee.

Across the study population, low-dose radiation therapy was associated with a 67% lower adjusted hazard of government-certified disability due to knee osteoarthritis. The largest apparent benefit was seen among patients with grade 2 disease, in which osteoarthritis was established but not yet advanced.

Results were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

“The most compelling part of this study is how the outcomes fit together,” said Bobby (Nagendra) Koneru, MD, FASTRO, a study author and a radiation oncologist at Loyola University in Maywood, Illinois.

“Patients experienced sustained improvement in pain and function, MRI showed less joint deterioration and years later, we saw less disability and, in patients with grade 2 disease, fewer knee replacements. Together, these findings raise the possibility that treatment may influence the longer course of osteoarthritis. That prospect makes it important to confirm in a larger multicenter study whether these findings represent a disease-modifying effect.”

Knee osteoarthritis develops as cartilage and other tissues within the joint break down, causing pain and difficulty with movement. Inflammation also contributes to the disease and may help drive its progression. Over time, damage to cartilage or bone can become irreversible, and some patients eventually need a knee replacement.

Treatment for knee osteoarthritis typically begins with exercise, weight management and medications or injections to relieve symptoms. These approaches can reduce pain and improve function, but most do not reliably slow structural progression of the disease.

Low-dose radiation therapy has been used for decades in parts of Europe and increasingly in the U.S. to relieve pain from osteoarthritis and other noncancerous inflammatory conditions. The doses are a small fraction of those used to treat cancer and are thought to work by reducing inflammation.

“Radiation therapy works differently at very low doses,” Koneru said. “In cancer treatment, we use much higher doses to kill cancer cells or keep them from growing. At the doses used for osteoarthritis, the goal is to reduce inflammation inside the joint.”

Previous research demonstrated that low-dose radiation therapy can improve short-term pain and physical function in patients with mild-to-moderate knee osteoarthritis. The current analysis examined whether improvement in symptoms aligned with structural changes inside the joint and longer-term outcomes.

The trial included 292 patients with symptomatic knee osteoarthritis classified as Kellgren-Lawrence grade 0, 1 or 2. This ranges from no definite osteoarthritis visible on X-ray to definite bone spurs and possible early joint-space narrowing; patients with grade 0 disease had evidence of osteoarthritis on MRI. Patients with more advanced grade 3 and 4 disease were excluded.

Participants were relatively young, with a median age of 38. They were randomly assigned to a single institution in Russia to receive glucosamine and chondroitin alone or the same medications plus low-dose radiation therapy totaling 4.5 Gy in 10 treatments. Radiation therapy was delivered with an orthovoltage machine using low-energy X-rays.

Both groups reported less pain immediately after treatment, but the benefit was sustained over time only for the radiation therapy group. Patients who received radiation therapy also reported significantly greater and more durable improvements in physical function and quality of life than those who received medication alone.

MRI scans tracked for three years after treatment also showed significantly less structural deterioration after radiation therapy. At 12 months, MRI scores showed slight improvement among patients who received radiation therapy, compared with worsening in the medication-only group. The significant difference between the groups persisted through the follow-up period.

Researchers also examined regional health records for knee replacement and government-certified disability due to knee osteoarthritis over a median follow-up of 11.9 years.

Across the study population, radiation therapy was associated with a statistically significant 67% lower adjusted hazard of disability. Koneru noted that this outcome reflects an independently certified consequence of knee disease, complementing the improvements in symptoms and MRI findings.

The largest absolute reduction in disability occurred among the 78 patients with grade 2 disease. Disability developed in 31% of those who received radiation therapy versus 61% of those who received medication alone. Knee replacement was performed in 14% versus 36%, respectively. Both differences were statistically significant.

“Grade 2 disease may represent a window where osteoarthritis is established but extensive joint damage has not yet occurred,” Koneru said. “The combination of less disability and fewer knee replacements in these patients is particularly encouraging. It suggests an opportunity to study whether treating inflammation earlier can change the longer course of the disease.”

The study has important limitations, Koneru noted. Participants knew whether they received radiation therapy, and the control group received medication rather than simulated radiation. The long-term outcomes and grade 2 subgroup analyses were exploratory; the difference in knee replacement across the full study population did not reach statistical significance.

Follow-up MRI data were incomplete, although the imaging readers were blinded. The trial was conducted at a single institution in Russia, where differences in health care delivery or access to knee replacement may limit how broadly the results apply.

No acute radiation reactions or cancers within the treated area were reported during follow-up. The study was not designed to quantify rare late effects or lifetime cancer risk, however, particularly in this relatively young population, and larger prospective studies are needed to assess long-term safety alongside durability of benefit.

Koneru said the next step for this research should be a multicenter randomized trial using simulated radiation therapy as the control, with prospectively defined imaging and long-term clinical endpoints and a focus on patients with grade 2 disease.

“For osteoarthritis, we have treatments that can help patients feel better, but much less evidence that they can change what is happening inside the joint. What makes these findings interesting is that the patient-reported improvement was accompanied by a measurable difference on MRI,” said 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.

“That moves the question beyond pain relief alone. 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.”

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Sadie Harley

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