Low-Dose Radiotherapy for Knee Osteoarthritis and the Growing Evidence Behind It

The Evidence for LDRT Did Not Begin With a Randomised Trial

Low-dose radiotherapy, or LDRT, for osteoarthritis can appear to be a new treatment.

It is not.

Radiotherapy has been used for painful benign musculoskeletal conditions in parts of Europe for many decades. What is relatively new is the effort to study the treatment using modern clinical trial methodology.

That distinction is important.

The evidence for LDRT has developed in stages.

It began with decades of clinical experience and large observational studies, particularly in Germany. More recently, treatment has been introduced into North American practice and evaluated using contemporary radiotherapy techniques. Randomised and sham-controlled trials have then asked a more difficult question.

Are patients improving because of the radiation itself, or because osteoarthritis symptoms naturally fluctuate and medical treatments can have substantial placebo effects?

The answer has not emerged in a straight line.

Some trials have been negative. Others have been encouraging. Newer studies have attempted to address weaknesses identified in earlier research.

Understanding LDRT therefore requires looking at how the evidence has evolved, rather than focusing on a single positive or negative trial.

Germany and Decades of Clinical Experience

Germany provides the starting point for much of the modern LDRT literature.

Unlike in many English-speaking countries, the use of radiotherapy for benign musculoskeletal conditions remained part of routine radiation oncology practice.

A national German patterns-of-care study gives some indication of the scale.

In 2014, participating German radiotherapy centres reported treating 14,936 patients with radiotherapy for osteoarthritis in a single year.

These included:

• 2,623 patients with knee osteoarthritis

• 2,230 with hip osteoarthritis

• 2,691 with shoulder osteoarthritis

• 2,440 with thumb-base osteoarthritis

• 2,297 with polyarthrosis

• more than 2,600 with other osteoarthritic conditions.

Thousands more were treated for conditions such as heel pain, shoulder syndromes and enthesopathies.

This tells us something important about the history of LDRT.

It was not an experimental treatment being occasionally offered by a handful of German centres. It had become a well-established part of clinical practice.

But widespread use does not itself prove that a treatment works.

For that, we need to look at outcomes.

What Did the Large German Series Show?

A frequently cited German study examined 1,037 patients with painful knee osteoarthritis who received LDRT between 1981 and 2008.

Across these patients, 1,659 courses of treatment were analysed.

Within two months of radiotherapy, 79.3% of treatment courses were associated with at least some degree of pain improvement, ranging from slight improvement through to complete pain relief.

That is an impressive clinical signal, particularly across more than one thousand patients.

Similar results were reported across numerous German retrospective and prospective series involving osteoarthritis and other painful musculoskeletal conditions.

German clinical guidelines subsequently incorporated LDRT for painful degenerative skeletal disorders, generally using individual fractions of approximately 0.5 to 1 Gy and total treatment doses in the range of 3 to 6 Gy.

There were also prospective studies.

One German prospective quality-assessment study followed 703 patients treated for several benign musculoskeletal conditions including knee osteoarthritis, heel pain, Achilles tendon pain, trochanteric bursitis and painful shoulder conditions.

Across the overall population, pain scores improved following treatment and some responses became more apparent with longer follow-up.

Interestingly, the pattern was not identical for every condition. The knee osteoarthritis group did not demonstrate the same increase in delayed response observed with some of the enthesopathy groups.

That is a useful reminder that LDRT should not be thought of as one treatment producing an identical response across every musculoskeletal condition.

What Could These Studies Tell Us?

Taken together, these studies suggested something clinically meaningful was occurring.

Across large numbers of patients, improvements in pain were being reported repeatedly.

But there was a significant scientific limitation.

Most of these studies did not include a control group.

Osteoarthritis symptoms fluctuate.

People also tend to seek additional treatment when their symptoms are particularly troublesome. Even without treatment, some of those symptoms may subsequently improve.

There is also a significant placebo response in studies of pain.

Therefore, if 70 or 80% of patients report feeling better after LDRT, it does not automatically follow that all of that improvement was produced by radiation.

By 2016, a systematic review reached essentially this conclusion.

The clinical studies suggested benefit, but the methodological quality of the available evidence was considered weak. The authors specifically called for properly designed, blinded and sham-controlled randomised trials using validated outcome measures.

That next stage of evidence was crucial.

The Dutch Trial Challenged the Existing Assumptions

In 2018, researchers in the Netherlands published one of the most important studies in the history of modern LDRT research.

They conducted a randomised, double-blind, sham-controlled trial in patients with symptomatic knee osteoarthritis who had not responded adequately to analgesics and exercise therapy.

Patients received either:

1 Gy per treatment for six treatments, giving a total dose of 6 Gy

or

sham treatment with no therapeutic radiation.

Only 55 patients were included, but the study design was much more rigorous than most previous observational research.

The result was striking.

At three months, approximately 44% of patients receiving LDRT responded, compared with approximately 43% receiving sham treatment.

There was essentially no difference.

Longer follow-up also failed to demonstrate a meaningful separation between the groups.

This trial could not simply be ignored.

For the first time, the improvement reported after radiotherapy looked very similar to improvement occurring after a simulated treatment.

It demonstrated why sham-controlled studies matter in a condition where pain can fluctuate considerably.

Did the Dutch Trial Prove That LDRT Does Not Work?

Not necessarily.

But it did show that the historical case-series evidence was insufficient to establish efficacy by itself.

A number of questions followed.

The study was relatively small.

The patient population differed from many earlier European series.

The treatment regimen was also different from the schedule increasingly used today. Patients received 1 Gy per treatment to 6 Gy, whereas many contemporary LDRT programs favour 0.5 Gy per treatment to a total dose of 3 Gy.

It is possible that dose, patient selection or other treatment factors contributed to the result.

But these remain potential explanations.

They should not be used to dismiss a properly conducted negative randomised trial.

Instead, the appropriate response was to design better studies that could investigate these questions directly.

ArthroRad Asked a Different Question

The German ArthroRad trial was another important step.

Rather than comparing radiotherapy with a true zero-radiation sham, researchers compared two different radiation doses in patients with knee and hand osteoarthritis.

Patients received either:

3 Gy using six 0.5 Gy treatments

or

0.3 Gy using six 0.05 Gy treatments.

Patients were unaware of which dose they received.

Both groups improved substantially over time.

However, there was no significant difference between the standard 3 Gy treatment and the much lower 0.3 Gy treatment, either in the initial analysis or at one-year follow-up.

That created another scientific puzzle.

There were several possible interpretations.

Perhaps both doses were biologically active.

Perhaps the radiation dose was less important than previously believed.

Or perhaps much of the improvement in both groups reflected nonspecific effects, natural variation in osteoarthritis symptoms or placebo response.

Because the comparator still received a small dose of radiation, ArthroRad could not completely resolve those possibilities.

What it did demonstrate was the need for trials capable of separating three things:

no radiation

an extremely low radiation dose

and

the standard therapeutic LDRT dose.

That is exactly the type of question newer studies have begun to address.

LDRT Begins to Re-Emerge in the United States

While this debate continued in Europe, something else began happening.

Interest in LDRT was returning to North America.

In 2025, Bobby Koneru, Richard Shaffer and colleagues published a contemporary American experience using LDRT for osteoarthritis.

The study included 69 patients and 168 treated joints.

Treatment was delivered using:

0.5 Gy per treatment for six treatments, giving a total dose of 3 Gy.

At completion of treatment, 80% of joints showed clinically meaningful pain improvement using the study’s response assessment.

At follow-up, 72% maintained meaningful improvement.

Approximately one third of treated joints went on to receive a second course, with additional pain improvement reported in selected patients.

This was important because it demonstrated that the clinical responses historically reported in European practice could also be observed in a modern American radiotherapy setting.

But again, there was a limitation.

It was a retrospective study without a sham control group.

It therefore strengthened the clinical signal, but it could not settle the central scientific question raised by the Dutch trial.

For that, additional randomised evidence was required.

Newer Randomised Evidence Begins to Appear

In 2025, researchers from Iran published another randomised study examining LDRT for knee osteoarthritis in older patients.

Patients receiving radiation were treated with 3 Gy over six fractions, the same overall dose now commonly used in contemporary LDRT programs.

Pain, function, performance status and analgesic use were followed for six months.

The radiation-treated group demonstrated significant improvements across these measures over follow-up, with no adverse effects reported in the study.

The authors concluded that 3 Gy LDRT may provide benefit for selected patients with knee osteoarthritis while also calling for further research.

This added another piece to the evidence base, but the study that attracted considerably more international attention was about to follow.

LoRD-KNeA Addressed Several Previous Questions at Once

The South Korean LoRD-KNeA trial represents an important development in contemporary LDRT research.

Rather than simply comparing radiotherapy with observation, it used a randomised sham-controlled design across three academic centres.

The trial included 114 patients with symptomatic knee osteoarthritis, predominantly Kellgren-Lawrence grade 2 or 3 disease.

Participants were allocated to one of three groups:

0 Gy sham treatment

0.3 Gy in six treatments

or

3 Gy in six 0.5 Gy treatments.

This design was particularly useful.

It included both a true sham group and the ultra-low 0.3 Gy dose that had previously created uncertainty in trials such as ArthroRad.

The results at four months showed a clear difference.

70.3% of patients receiving 3 Gy met the predefined OMERACT-OARSI criteria for clinical response.

In the sham group, the response rate was:

41.7%.

The 0.3 Gy group had a response rate of 58.3%, but this was not statistically significantly different from sham.

A clinically meaningful improvement in the WOMAC assessment of pain, stiffness and physical function was also more frequent following 3 Gy treatment, occurring in 56.8% compared with 30.6% following sham treatment.

No treatment-related toxicity was reported during the initial study period.

Why Is LoRD-KNeA Important?

The importance of the study is not simply that it was positive.

It addressed questions created by the preceding evidence.

Large German series had suggested that LDRT worked.

The Dutch trial had shown that improvement could be almost identical after sham treatment.

ArthroRad had shown similar improvement after both 3 Gy and 0.3 Gy, leaving open the possibility that either both radiation doses worked or neither was substantially different from nonspecific improvement.

LoRD-KNeA included all three relevant groups.

No radiation.

Very-low-dose radiation.

And the contemporary 3 Gy treatment schedule.

Only the 3 Gy group demonstrated a statistically significant improvement over true sham treatment for the primary clinical response endpoint.

That does not mean every question has been answered.

The study contained 114 patients, follow-up for the initial report was relatively short, and not every secondary outcome showed a significant difference.

But it represents an important progression in the quality of evidence supporting LDRT.

What About Systematic Reviews and Meta-Analyses?

This is where the chronology becomes particularly important.

A systematic review and meta-analysis published in 2025 included 12 studies involving 1,750 participants, with six studies contributing to the quantitative meta-analysis.

Its pooled analysis found no statistically significant advantage for LDRT over sham treatment for pain or physical function.

The authors concluded that the evidence did not support routine use of LDRT over established therapies and recommended that treatment remain investigational or be considered in selected refractory cases.

That is an important result and should be acknowledged.

However, evidence reviews are necessarily limited to the research available when their literature search closes.

The search for that meta-analysis ran through June 2025.

The initial LoRD-KNeA randomised results were not publicly presented until the ASTRO Annual Meeting in September 2025.

The meta-analysis therefore could not incorporate one of the most important newer sham-controlled trials.

That does not make the meta-analysis incorrect.

It demonstrates how quickly this area of research is changing.

A Field Moving From Observational Evidence to Randomised Evidence

Looking at the literature in chronological order helps explain why different clinicians can reach different impressions of LDRT.

Someone looking primarily at decades of German experience sees thousands of patients and repeatedly reported response rates in the region of 70 to 80%.

Someone looking primarily at the first Dutch sham-controlled study sees almost no difference between radiation and placebo.

Someone looking at ArthroRad sees similar improvement after standard-dose and ultra-low-dose radiation.

And someone looking at LoRD-KNeA sees a contemporary sham-controlled trial in which the standard 3 Gy regimen produced a significantly higher clinical response than sham.

These findings do not need to be forced into a simple narrative in which every study agrees.

Scientific evidence often develops by identifying weaknesses in earlier studies and then designing the next study to address them.

That appears to be what is happening with LDRT.

Contemporary North American Guidance

Another indication that the evidence base is changing came in 2026.

The American Radium Society published multidisciplinary Appropriate Use Criteria for LDRT in osteoarthritis.

The committee included radiation oncologists, rheumatologists, orthopaedic specialists and a patient advocate.

Using systematic review methodology, it considered more than 50 eligible studies across different levels of methodological quality.

Across the broader literature, the review reported overall treatment response rates of approximately 60% to 90%, with reported improvements in pain, mobility and quality of life.

Importantly, the authors also concluded that further high-quality studies remain necessary.

That balance is important.

The emergence of contemporary guidance does not mean the evidence debate is over.

It means that LDRT has accumulated enough contemporary evidence to warrant structured multidisciplinary assessment of where it may fit into osteoarthritis care.

The Next Generation of Trials Is Already Underway

The evidence is continuing to evolve.

At the 2026 American Society for Radiation Oncology Annual Meeting in Boston, a new randomised trial of LDRT for knee osteoarthritis has been selected for the Clinical Trials Session.

The study is being presented by Dr Bobby Koneru and is titled:

Randomized Trial of Low-Dose Radiotherapy for Knee Osteoarthritis Patient-Reported, Structural and Long-Term Clinical Endpoints

It is scheduled for presentation on 27 September 2026 and has also been selected for ASTRO’s official Annual Meeting press program.

At the time of writing, the results have not yet been presented.

The study is particularly interesting because the title indicates that researchers are moving beyond short-term pain scores to investigate long-term clinical outcomes and structural changes within the osteoarthritic knee.

These are exactly the questions the field now needs to answer.

Does improvement last?

Which patients benefit most?

Does the stage of osteoarthritis matter?

Does treatment affect anything beyond pain?

Can imaging or biological features help identify likely responders?

And what is the optimal radiation dose and treatment schedule?

So Does LDRT Work for Osteoarthritis?

The most accurate answer is more nuanced than either a simple yes or no.

There is a substantial history of clinical use, particularly in Germany.

Large observational studies have repeatedly reported improvements in pain following treatment.

Modern American experience has demonstrated similar responses using contemporary radiotherapy.

Early sham-controlled research challenged the assumption that all of this improvement was caused by radiation.

Dose-comparison studies raised further questions.

More recent randomised evidence, particularly LoRD-KNeA, has now provided encouraging evidence that 3 Gy delivered as six 0.5 Gy treatments can produce clinically meaningful improvement beyond sham treatment in selected patients with knee osteoarthritis.

At the same time, systematic reviews have highlighted heterogeneity between studies and the limitations of the overall evidence base.

Both of these things can be true.

The evidence supporting LDRT is becoming stronger, while further high-quality research remains necessary.

Why Patient Selection May Matter

One of the important lessons emerging from modern studies is that osteoarthritis should not be treated as a single uniform condition.

The degree of structural damage varies.

The amount of inflammation varies.

The duration and character of symptoms vary.

A patient with moderate osteoarthritis, persistent pain and an inflammatory component may represent a very different biological situation from someone with severe joint destruction and predominantly mechanical symptoms.

LoRD-KNeA concentrated on patients with Kellgren-Lawrence grade 2 and 3 disease, which is particularly relevant when considering how its results should be applied.

As research progresses, determining who is most likely to respond may prove just as important as determining whether LDRT works on average across a broad population.

Where We Are Now

The story of LDRT for osteoarthritis is not one of a forgotten treatment suddenly being rediscovered and proven by a single study.

It is a much more interesting scientific progression.

Decades of German clinical experience produced a consistent signal of pain improvement.

Large observational studies strengthened that signal but could not exclude placebo effects and natural variation in symptoms.

The first sham-controlled trial challenged the field.

Dose-comparison studies raised further questions.

Contemporary American experience demonstrated that similar responses could be observed outside Europe.

Newer randomised trials have begun to provide more encouraging controlled evidence, with LoRD-KNeA showing a significant benefit for the contemporary 3 Gy regimen compared with sham treatment.

Multidisciplinary guidance is now emerging, and another generation of prospective trials is investigating longer-term and structural outcomes.

The evidence has therefore not developed in a straight line.

That is not a weakness of medical research.

It is how a treatment moves from clinical observation toward a more rigorous understanding of when it works, how well it works and which patients are most likely to benefit.

LDRT at Pinpoint Radiotherapy

At Pinpoint Radiotherapy, LDRT is not presented as a treatment that will work for every person with osteoarthritis.

Patients are assessed individually, taking into account:

• the joint involved

• severity of symptoms

• duration of symptoms

• imaging findings

• degree of structural osteoarthritis

• treatments already tried

• age and general health

• other possible causes of pain.

Where LDRT is appropriate, a commonly used contemporary regimen is:

0.5 Gy per treatment for six treatments

giving a total dose of:

3 Gy.

This is the same total dose investigated in modern studies including LoRD-KNeA and contemporary North American series.

Some patients experience substantial improvement, some have a partial response and some do not respond.

Our approach is therefore to discuss both the potential benefits and the limitations of the current evidence, rather than promising a particular outcome.

For selected patients with persistent symptomatic osteoarthritis despite appropriate conservative treatment, LDRT represents an additional treatment option supported by a substantial historical experience and an increasingly rigorous modern evidence base.