Low-Dose Radiation Therapy for Peripheral Joint Osteoarthritis: Early United States Community Experience With Pain, Function, and Medication Outcomes

Abstract

Purpose

This study aimed to evaluate the real-world effectiveness and feasibility of low-dose radiation therapy (LDRT) for peripheral joint osteoarthritis (OA) in a United States community oncology setting, focusing on pain, function, and analgesic outcomes.

Methods and Materials

We retrospectively analyzed 30 consecutive patients (55 joints) treated with LDRT (3 Gy in 6 fractions; 0.5 Gy per fraction) for OA. Pain was assessed using a 0 to 10 numeric rating scale. Global improvement was captured with the von Pannewitz score (0-4; lower = greater improvement). Analgesic change was abstracted from the medical record. Paired tests compared pre- and posttreatment outcomes.

Results

Mean baseline pain was 8.1 ± 1.4, improving to 3.5 ± 1.7 at early follow-up (Δ−4.6; P < .001). von Pannewitz score indicated improvement in 92% of treated joints. Twenty-three percent of patients reduced analgesic use; none required analgesic escalation. All patients completed treatment without interruptions, and no acute toxicities were recorded.

Conclusions

In a community oncology setting, LDRT was feasible and associated with clinically meaningful reductions in pain and analgesic use for peripheral joint OA. These findings support prospective trials to validate benefits and define optimal patient selection and retreatment strategies.

Introduction

Osteoarthritis (OA) is a leading cause of disability and health care utilization among older adults in the United States.1, 2, 3 Conventional management typically begins with lifestyle modification, physical therapy, and nonsteroidal anti-inflammatory drugs, with intra-articular injections and surgery reserved for refractory cases. Surgical management and pharmacologic interventions can be effective but carry procedural and systemic risks.² Yet, many patients experience limited pain relief, medication intolerance, or lack access to timely orthopedic intervention. Emerging evidence suggests that low-dose radiation therapy (LDRT) may exert anti-inflammatory and analgesic effects in degenerative and inflammatory musculoskeletal conditions.4, 5, 6 Although widely practiced in parts of Europe, adoption in the United States (US) has been limited by historical and evidentiary factors.^4,6

Recently, modern series have demonstrated clinically meaningful pain reductions with LDRT across multiple joint sites using standardized fractionation (3 Gy in 5 or 6 fractions per series), with acceptable safety and the potential benefit of a second series in selected cases. Building on this literature, we report an early community oncology experience implementing LDRT for peripheral joint OA, emphasizing pain relief, patient-assessed improvement, and changes in analgesic use.

Methods and Materials

Study design and oversight

We performed a retrospective analysis of consecutive patients treated with LDRT for symptomatic peripheral joint OA in a community oncology setting between 2023 and 2025. The study followed institutional policies for retrospective research, including privacy safeguards, and it was approved by the institutional review board (UNLV IRB #UNLV-2025-460).

Eligibility

Adults with clinically and/or radiographically confirmed peripheral joint OA were eligible if they experienced persistent pain despite conservative therapy, including nonsteroidal anti-inflammatory drugs, physical therapy, and/or intra-articular injections. Patient selection reflected routine physician-directed clinical practice rather than predefined prospective study criteria. Exclusion criteria included active malignancy within the treatment field, pregnancy, age <50 years, and axial skeleton or pelvic sites. Referral for LDRT occurred at the discretion of the treating radiation oncologist after documented failure, intolerance, or patient preference against further pharmacologic escalation or surgical intervention. Table 1 shows the patient and treated joint characteristics.

Table 1.

Patient and treated joint characteristics (N = 30 patients, 55 joints)

Characteristic	Value
Age (y), median (range)	76 y (54-93)
Sex, n (%)	Female, 21 (70%); Male, 9 (30%)
Baseline analgesic use	100% of patients
Prior therapies	NSAIDs, physical therapy, and/or intra-articular injections
Treated joints per patient	Median 2 (range, 1-4)
Joint location, n(%)	Knee 31 (56%) Hip 7 (13%) Hand 6 (11%) Shoulder 6 (11%) Ankle/other peripheral 5 (9%)

Joint counts reflect clinically treated joints; some patients received treatment to multiple joints.

Abbreviation: NSAID, nonsteroidal anti-inflammatory drug.

Radiographic severity grading (eg, Kellgren-Lawrence classification) was not uniformly available due to external referral patterns and variability in prior imaging documentation; therefore, formal severity stratification was not performed.

Treatment

Patients received LDRT to a total dose of 3 Gy delivered in 5 to 6 fractions (0.5 Gy per fraction) on nonconsecutive days. All treatments were computed tomography–simulated and planned using 3-dimensional conformal radiation therapy with photon energies ranging from 6 to 18 MV, tailored to joint size, depth, and surrounding anatomy. Table 2 shows the radiation treatment and follow-up characteristics.

Table 2.

Radiation treatment and follow-up characteristics

Parameter	Description
Total dose/fractionation	3 Gy total in 5-6 fractions (0.5 Gy/fraction)
Fractions delivered	6 fractions in 29 patients; 5 fractions in 1 patient
Energy	6-18 MV photons
Simulation and planning	CT-simulated with 3-dimensional conformal radiation therapy planning
Immobilization	Joint-specific positioning devices as needed
Bolus use	Applied when appropriate for superficial joints (eg, hand)
Second LDRT course	None; all 55 treated joints received first-course LDRT
Median follow-up time	7 wk (range, 5-14 wk)
Outcome reporting unit	Per treated joint

Abbreviations: CT = computed tomography; LDRT = low-dose radiation therapy.

Joint-specific immobilization devices were used as needed. Surface bolus was applied when appropriate for superficial joints, such as the hand, to ensure adequate dose coverage of the joint capsule. Radiosensitive structures were shielded when feasible.

No treated joints in this cohort represented retreatment; all 55 joints received first-course LDRT.

Assessments

Pain intensity was assessed using a 0 to 10 numeric rating scale (NRS), a validated patient-reported outcome measure that captures the patient’s primary pain component, defined as the most relevant or bothersome aspect of their pain. The NRS is widely used in both clinical practice and OA research because it is simple to administer, can be completed verbally or in writing, and is sensitive to clinically meaningful changes in pain severity over time. The NRS has demonstrated strong reliability and validity in OA populations and has been used to evaluate treatment effectiveness in observational and interventional studies of knee and hip OA.7, 8, 9, 10

Global improvement was assessed using the von Pannewitz score (VPS), a categorical physician-assessed response scale commonly used in LDRT studies for benign musculoskeletal conditions, defined as follows: 0 = complete response (pain-free), 1 = marked improvement, 2 = moderate improvement, 3 = no change, and 4 = worsening of symptoms.^11,12

Follow-up assessments were abstracted primarily from radiation oncology clinic documentation. When available, follow-up information from referring providers, including primary care and orthopedic notes, was reviewed to corroborate symptom trajectory and analgesic use.

Early follow-up was defined as the first posttreatment clinical assessment occurring within 4 to 14 weeks after completion of LDRT (median, 7 weeks). When multiple assessments occurred within this window, the best reported pain score was used for analysis, consistent with prior LDRT OA series. Outcomes were analyzed per treated joint.

Statistics

Descriptive statistics were used to summarize patient and treatment characteristics. Paired t tests compared baseline versus follow-up NRS. VPS distributions and analgesic changes were reported descriptively. Statistical significance was set at 2-sided P < .05. Outcomes were analyzed on a per-treated-joint basis. Because multiple joints were treated in several patients, formal adjustment for within-patient clustering was not performed. This may introduce correlation between observations and represents a statistical limitation of the analysis. Exploratory analysis performed at the patient level demonstrated similar direction and magnitude of effect.

Results

Cohort

Thirty patients (55 treated joints) received first-course LDRT. The most frequently treated sites were the knee and hand, followed by hip and shoulder. No joints represented retreatment. All patients completed radiation without interruption.

Pain relief

Mean NRS improved from 8.1 ± 1.4 at baseline to 3.5 ± 1.7 at early follow-up (mean change −4.6; P < .001). The median reduction in NRS was −4 points (IQR, −5-−3), corresponding to a large standardized effect size (Cohen’s d = 2.9). Table 3 shows the pain and analgesic outcomes after LDRT for osteoarthritis

Table 3.

Pain and analgesic outcomes after LDRT for osteoarthritis (N = 30 patients, 55 joints)

Measure	Baseline	Follow-up	Change/result
NRS (0-10)	8.1 ± 1.4	3.5 ± 1.7	Δ −4.6, P < .001
VPS improved (%)	–	92%	–
Analgesic use decreased (%)	–	23%	7 of 30 patients reduced use
Analgesic escalation (%)	–	0%	None escalated

Values are expressed as mean ± SD, unless otherwise indicated. VPS, 0-4; lower = greater improvement. Analgesic use based on documentation of pain medication changes between baseline and follow-up.

Abbreviations: LDRT = low-dose radiation therapy; NRS = numeric rating scale; VPS = von Pannewitz score.

Global improvement

VPS indicated improvement (scores 0-2) in 92% of treated joints at early follow-up.

Analgesic use

Seven of 30 patients (23%) reduced analgesic use; no patients required escalation.

Safety

There were no acute radiation toxicities or unplanned treatment breaks.

Discussion

In this US community experience, LDRT for peripheral joint OA was feasible and associated with clinically meaningful reductions in pain and analgesic reliance. The magnitude of early pain relief (Δ−4.6 on a 0-10 scale) is consistent with effect sizes reported in contemporary series using similar dosing schemas from academic and community settings. These results align with emerging randomized evaluations of LDRT in OA, including the Fazilat-Panah trial,¹³ although effect magnitude and durability vary across studies. The 92% global improvement rate by VPS and the absence of analgesic escalation are consistent with a clinically meaningful signal, although the absence of a control arm precludes definitive causal attribution. All outcomes in this series reflect first-course LDRT, allowing interpretation of treatment effect without confounding from retreatment.

These findings align with modern single-institution series demonstrating significant pain reduction across joint sites and support that benefits may be observed early in the posttreatment window. Mechanistically, low-dose irradiation modulates inflammatory pathways and immune cell composition, providing a biologic rationale for symptomatic improvement in OA. These findings are further supported by long-term orthovoltage series and mechanistic analyses.^14,15 The absence of acute toxicity and uninterrupted treatment in our cohort mirrors the favorable safety profile reported in the literature13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and a minimal long-term risk of radiation-induced toxicity.¹⁶

A recently reported multicenter randomized, sham-controlled trial from Korea building on the (LoRD-KNeA, Low-dose RaDiation therapy for patients with KNee osteoArthritis) protocol and related preliminary findings presented at ASTRO 2025^17,18 included 114 patients with mild-to-moderate knee OA. Total doses of 0.3 Gy or 3 Gy in 6 fractions had a significantly higher responder rate in the 3 Gy arm (70.3 %) versus sham (41.7 %; P = .014) at 4 months, with meaningful improvement in Western Ontario and McMaster Universities Arthritis Index (WOMAC) total score in 56.8 % versus 30.6 % in the sham arm (P = .024). These data suggest a potential dose-response relationship in favor of a 3 Gy regimen and support the feasibility of rigorous controlled trials in this domain. Our community-based series (Δ pain −4.6 NRS) aligns with these findings and suggests that LDRT may be broadly translatable beyond academic settings. However, unlike the Korean trial, which restricted analgesics during the first 4 months, our real-world cohort allowed standard analgesic use (with only abstracted usage changes). Thus, our findings complement and extend the emerging evidence base. The Korean study did not yet demonstrate significant analgesic-reduction endpoints or long-term structural imaging outcomes, so our study’s emphasis on analgesic use reduction (23%) adds novel real-world context. Longer-term follow-up and imaging-correlated endpoints remain key outstanding questions, as the Korean trial authors note.^17,18 Taken together, the combined evidence strengthens the rationale for LDRT as a viable nonpharmacologic and nonsurgical adjunct in patients with mild-to-moderate peripheral joint OA, but highlights the ongoing need for prospective randomized studies to establish durability, optimal dose/fractionation, and refined patient selection criteria.

This analysis has several limitations, including its retrospective design, modest cohort size, nonrandomized setting, and short follow-up duration, which preclude definitive conclusions regarding durability. The absence of a control or sham arm introduces the possibility of placebo effects. Given the well-documented placebo response observed in OA pain trials, the magnitude of improvement reported here must, therefore, be interpreted cautiously. Additionally, follow-up was limited to early posttreatment assessment (median, 7 weeks), and durability beyond this interval cannot be determined from the present analysis. Follow-up timing was not standardized, and outcome assessment relied on routine clinical documentation rather than uniform prospective patient-reported outcome instruments. Although analgesic reduction was abstracted from the medical record as a pragmatic real-world functional surrogate, validated functional instruments (eg, WOMAC and Knee Injury and Osteoarthritis Outcome Score) were not systematically collected. Radiographic disease severity and structural imaging outcomes were not systematically captured. The low rate of retreatment in this cohort likely reflects limited follow-up duration and evolving clinical practice patterns rather than definitive absence of symptom recurrence. Accordingly, these findings should be interpreted as hypothesis-generating observational data reflecting real-world community practice rather than confirmatory evidence of efficacy.

Future work should incorporate validated patient-reported outcome instruments (eg, WOMAC and Knee Injury and Osteoarthritis Outcome Score), standardized timing of follow-up, and eligibility enrichment (eg, excluding advanced deforming OA unlikely to respond). Pragmatic designs that allow a second series based on early symptom trajectory may better reflect routine clinical practice and could clarify the role of retreatment. Ongoing international randomized studies, including Investigation of the Clinical Efficacy of Low-dose Ionizing Radiation in the Treatment of Osteoarthritis (IMMO-LDRT02),¹⁹ will help resolve remaining uncertainty regarding dose-response relationships, patient selection, and the magnitude of benefit relative to sham or standard care.

In the context of constrained analgesic strategies and surgical backlogs for older adults with OA, LDRT may represent an accessible, noninvasive adjunct in multidisciplinary care when applied judiciously and within evidence-informed parameters.

Conclusions

LDRT was safe and feasible and was associated with substantial early reductions in patient-reported pain and decreased analgesic use in this US community cohort. These findings support continued prospective evaluation of LDRT in controlled trials and provide a pragmatic template for responsible implementation in community oncology practice.

Declaration of AI and AI-Assisted Technologies in the Writing Process

During the preparation of this work the authors used ChatGPT in order to improve text readability, correct grammatical errors, and format the manuscript according to the journal's guidelines. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Disclosures

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.