Patients with early, painful knee osteoarthritis had a 67% lower rate of disability if they received low-dose radiation along with glucosamine and chondroitin supplements compared with those who only received the same supplements, according to long-term data from an extension of a randomized trial presented at the American Society for Radiation Oncology (ASTRO) 2026 Annual Meeting.

“What we found was that patients that had low-dose radiation therapy for early-stage osteoarthritis of the knee had durable pain response with low-dose radiation therapy, overall better quality of life, less damage on MRI at 1 and 3 years, less progression of disease at 10-year imaging, less disability, and also fewer knee replacements for grade 2 disease,” Bobby N. Koneru, MD, radiation oncologist at Stritch School of Medicine, Loyola University in Chicago, and MercyOne Dubuque Cancer Center in Dubuque, Iowa, told attendees. “The concordance of all of these findings is what makes this very interesting and powerful. It sends a strong signal and ultimately validates that we need to have a confirmation multicenter randomized study here in the United States.”

However, the study included several substantial limitations that amounted to “fatal flaws,” Joel A. Block, MD, professor of medicine and director of the Division of Rheumatology at Rush University Medical Center in Chicago, told Medscape Medical News. The trial was an extension of a randomized, open-label trial published in 2023 that Block had already critiqued in a perspective article published in August in Arthritis & Rheumatology. “Osteoarthritis pain is exceptionally susceptible to the placebo effect,” Block wrote at the time, with formal pain trials consistently revealing “an extremely potent placebo response” of generally at least 40% and a “very high effect size” as high as 0.8, depending on the joints involved.

Block and Koneru both agree that there has long been a significant unmet need for pain control of osteoarthritis, and Koneru pointed to the need as well for finding ways to prevent progression of the disease. “Current treatments for early disease ease symptoms, but currently there has been no treatment to actually slow or modify the disease,” he told attendees.

Should the Results Prompt a US Sham-Controlled Randomized Trial?

Although low-dose radiation therapy has been used for decades, primarily in Europe, to relieve joint pain, he said, evidence from randomized controlled trials has remained sparse, with even less data for long-term outcomes. “The key question that we are asking is if low-dose radiation therapy can change the long-term course of knee osteoarthritis,” he said.

Koneru therefore presented data on an extension of a randomized trial in Arkhangelsk, Russia, that enrolled 292 patients with early, painful knee osteoarthritis (grade 0-2) between 2012 and 2014. The patients’ median age was about 38 years, and all received an x-ray and MRI before treatment. Half the patients were randomly assigned to receive supplemental glucosamine and chondroitin, while the other half received those supplements as well as 10 low-dose treatments of radiation spread over 3 weeks that totaled 4.5 Gy.

Outcomes included joint damage on MRI at 1 and 3 years and on x-ray at 10 years, pain and function through 3 years, and disability and knee replacement over up to 13 years. The imaging was read by radiologists who were blinded to the treatment groups, and disability was assessed by an independent government commission that was similarly blinded to treatment.

The original findings of the trial, previously published, showed that 25% of those receiving only supplements reported meaningful pain relief at 3 years compared with 69% of those who received low-dose radiation (P < .0001). About a third of those who received supplements alone (36%; 39 of 108 patients) showed marked worsening on x-ray at 10 years compared with 3% (3 of 99 patients) of those who received low-dose radiation (P = .003). 

The new long-term results included follow-up for a median of 11.9 years in 253 patients. Government-certified disability due to knee osteoarthritis was reported in 25% of those who received only supplements compared with 14% of those who received low-dose radiation (hazard ratio [HR], 0.33; 95% CI, 0.18-0.59; P < .001).

Among patients with grade 2 disease, 61% of those receiving supplements alone had disability compared with 31% of those receiving supplements and low-dose radiation, resulting in a number needed to treat of 3-4 patients for 1 patient spared disability (P = .005), Koneru reported.

Although knee replacement rates were lower for patients receiving low-dose radiation (8%) than supplements alone (16%), the difference was not significant (P = .089). When comparing patients with grade 2 disease, however, the results were significant, with 36% of those in the supplements-only group getting a knee replacement and 14% of the low-dose radiation group getting one (HR, 0.32; 95% CI, 0.12-0.84; P = .021).

Gopal K. Bajaj, MD, MBA, co-chair of ASTRO’s Functional Radiation Medicine Task Force and a radiation oncologist at Inova Schar Cancer Institute in Fairfax, Virginia, said in a formal statement that the measurable differences in MRI findings are what make these findings compelling.

“That moves the question beyond pain relief alone,” Bajaj said. “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.”

‘Fatal Flaws’

Koneru acknowledged that the study’s biggest limitations were being an open-label study at a single institution.

“Patients did know what treatment they were getting, so that may add a little bit of bias into this,” Koneru said. “The ideal study would be a completely sham-controlled, randomized study where the patients didn’t know at all if they were getting radiation, and long follow-up, just like this study had.”

Block noted in his article, however, that in addition to the lack of a sham control, “the study population did not represent a generalizable osteoarthritis study, as more than 70% of the study cohort had radiographic Kellgren-Lawrence grades of 0 or 1, and the rest were Kellgren-Lawrence grade 2.” He expressed skepticism about how the rates of disability were reported.

“Despite a group with exceptionally mild osteoarthritis at baseline, between 9.5% and 17.8% of the patients had progressed to disability during this time frame” of 10 years, he wrote. “Although these differences were statistically significant, it is unclear what the basis was for such dramatic progression of early osteoarthritis in this group and whether knowledge of the low-dose radiation therapy treatment influenced the diagnosed disability.”

In reference to the updated findings, he told Medscape Medical News that “there are obvious fatal flaws,” as there were in the main study. “I think that any dispassionate analysis would conclude that this study does not present a compelling case for low-dose radiation therapy efficacy.”

Koneru suggested that low-dose radiation should still remain an option for people with early knee osteoarthritis, albeit not first-line.

“Currently, in our treatment landscape, patients first are managed conservatively with exercise, weight loss, physical therapy. If that fails, they will receive pain medications like NSAIDs [nonsteroidal anti-inflammatory drugs] and Tylenol, and if that fails, there are other options that are slightly more invasive, like steroid injections,” he said. “I call this the care gap, and that’s where low-dose radiation therapy currently sits,” typically reserved for mild-to-moderate disease since patients with more advanced disease would need knee replacement. “What this study has shown, though, is that perhaps we should be treating them earlier,” he added. “That that’s where potentially the biggest gain can be found.”

The study received no external funding. Koneru reported being chief medical officer and an equity holder in JointGlow and serving on an advisory board for Varian Medical Systems. Block reported consulting for Apos USA, Haleon, Eupraxia Pharmaceuticals, and PK Med. 

Tara Haelle has been an independent science/health journalist for over 15 years, with work appearing in over two dozen trade and consumer publications. She is the author of Vaccination Investigation: The History and Science of Vaccines and The Informed Parent: A Science-Based Resource for Your Child’s First Four Years. Haelle is the public health beat leader for the Association of Health Care Journalists, where she develops resources to help other journalists report on medical studies and public health. She is based in Dallas.