Cultural bias in pain treatments❓

Osteoarthritis is in my left knee. I stopped playing hockey 4 years ago - the pain and swelling never stopped during hockey season. After a PRP treatment, my knee has been normal for 3 years.

About Low-Dose Radiation Therapy (LDRT)

I appreciate what a single PRP injection did for me. However, it doesn’t work for everyone. Each body is different and the circumstances of the pain problem will always be unique to each person.

In Germany, they have PRP, but they also have LDRT.

My brother called me recently to ask for the contact information of the Sports Medicine doctor who administered a PRP treatment on my left knee a few years ago. I also told him what I had learned about LDRT and expressed my hope that this alternative treatment may now be administered by her, but I am doubtful. I had listened to Episode #345 ‒ Chronic pain: pathways, treatment, and the path to physical and psychological recovery with Sean Mackey, M.D., Ph.D. Sean explained its absence in the American market, to his dismay, but things may be changing south of our border.

In October, 2022, the paper ‘The Use of Low-Dose Radiation Therapy in Osteoarthritis: A Review’ appeared in PubMed indicating some interest for the American market. Perhaps if it succeeds there, Canadian authorities may finally allow the LDRT market to grow here⁉️ I’m not holding my breath 🥺.

Curious, I asked GROK the following question,

🧶 In Germany, low-dose radiation treatments are available to address pain associated with osteoarthritis, tendinitis, and muscular-skeletal injuries. This has been available to Germans for decades. Clinical results and German scientific studies support its use but it has not been available in the USA or Canada. Please explain why. Also, provide summaries of the most compelling published papers that explain this treatment’s efficacy.

🕵️‍♂️ GROK replied.

Why Low-Dose Radiation Therapy (LDRT) Is Not Available in the USA or Canada

Low-dose radiation therapy (LDRT) has been used in Germany and parts of Europe for decades to treat painful conditions like osteoarthritis (OA), tendinitis, and musculoskeletal injuries, with clinical and scientific support for its efficacy. However, its adoption in the United States and Canada is minimal due to a combination of historical, cultural, scientific, and regulatory factors:

1. Historical Shift Away from LDRT:

   • In the early 20th century, LDRT was used globally, including in the USA, for inflammatory conditions like arthritis. However, after the 1940s, concerns about radiation risks (e.g., cancer induction following atomic bomb exposures) and the rise of effective pharmaceuticals (e.g., NSAIDs, corticosteroids) led to its decline.

   • By the 1980s, improved pharmacologic options and negative results from some controlled trials (using outdated dosing protocols) further diminished LDRT’s use in North America, while Germany continued its clinical application and research.

2. Radiophobia and Public Perception:

   • Fear of radiation, fueled by historical events and media portrayals, has created a cultural bias against radiation-based treatments in the USA and Canada. Even though LDRT uses doses comparable to diagnostic imaging (e.g., an abdominopelvic CT scan), public and medical skepticism persists.

   • This contrasts with Germany, where LDRT is normalized, with over one-third of radiotherapy treatments for benign conditions like OA.

3. Lack of Modern Clinical Trials in North America:

   • Most contemporary evidence supporting LDRT comes from European studies, particularly Germany, where the German Society of Radiation Therapy and Oncology (DEGRO) and the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) have systematized research since 1995.

   • In the USA and Canada, limited funding and interest in studying “old” therapies, coupled with a preference for novel biologics or surgical interventions, have stalled LDRT research. Early negative trials (e.g., 1975 studies with non-optimal dosing) further discouraged investigation.

4. Regulatory and Insurance Barriers:

   • In the USA, LDRT for OA is not widely covered by insurance due to its non-standard status, requiring prior authorization or out-of-pocket costs.

   • Regulatory bodies like the FDA and Health Canada prioritize treatments with robust, local randomized controlled trials (RCTs), which are scarce for LDRT in North America, limiting its integration into clinical guidelines.

5. Medical Training and Infrastructure:

   • North American medical curricula rarely cover LDRT for benign conditions, and radiation oncologists are primarily trained for cancer treatment. In contrast, German radiation oncologists are familiar with LDRT protocols for OA and tendinitis, supported by national guidelines.

   • The lack of standardized care paths and dedicated programs in the USA and Canada hinders adoption, unlike Cleveland Clinic’s recent initiative to create a prospective registry.

6. Scientific Skepticism:

   • Some North American researchers cite negative RCTs (e.g., Minten et al., 2018) that failed to show LDRT’s benefit, though these studies often had limitations like short follow-up or suboptimal patient selection.

   • The absence of a clear mechanistic consensus (despite evidence of anti-inflammatory effects) fuels skepticism among evidence-based medicine advocates.

Summaries of Compelling Published Papers on LDRT Efficacy

Below are summaries of key peer-reviewed papers, primarily from German and European studies, that highlight LDRT’s efficacy for osteoarthritis, tendinitis, and musculoskeletal injuries. These papers were selected for their robust data, large sample sizes, or significant contributions to understanding LDRT’s mechanisms and clinical outcomes.

1. Rühle et al. (2021): “Low-dose radiotherapy for painful osteoarthritis of the elderly: A multicenter analysis of 970 patients with 1185 treated sites”

   • Study Design: Retrospective multicenter analysis of 970 elderly patients (aged 65+) treated with LDRT for OA at 1185 joint sites in Germany, assessing pain relief using the Numerical Rating Scale (NRS) and von Pannewitz Score (VPS).

   • Key Findings:

     • Two-thirds of patients reported pain improvement post-LDRT, with significant NRS reductions from 66.1–66.9 pre-treatment to lower scores at the end of treatment (t1) and first follow-up (t2) (p < 0.001).

     • No differences in efficacy across age groups (young old: 65–74, older old: 75–84, oldest old: ≥85), suggesting no upper age limit for treatment.

     • Pain response was consistent across joint sites (e.g., knee, hip, hand), with no significant gender or fractionation differences (0.5 Gy vs. 1 Gy per fraction).

     • Minimal toxicities were reported, reinforcing LDRT’s safety profile.

   • Mechanisms: LDRT’s anti-inflammatory effects modulate immune responses, reducing proinflammatory cytokines and macrophage activity.

   • Significance: This is the largest study of elderly OA patients, demonstrating LDRT’s effectiveness and safety, particularly for those refractory to conventional treatments. It supports its role as a non-invasive option with socioeconomic benefits.

2. Hautmann et al. (2020): “Prospective Evaluation of Changes in Pain Levels, Quality of Life and Functionality After Low Dose Radiotherapy for Epicondylitis, Plantar Fasciitis, and Finger Osteoarthritis”

   • Study Design: Prospective trial in Germany evaluating LDRT (3 Gy in 6 fractions at 0.5 Gy or 6 Gy in 6 fractions at 1 Gy) for 20 patients with epicondylitis (tendinitis), plantar fasciitis, or finger OA, using NRS, WOMAC, and quality-of-life metrics.

   • Key Findings:

     • Significant pain reduction at 6–12 weeks post-treatment (p < 0.05), with sustained improvements at 9–12 months for NRS, WOMAC, and functional scores.

     • For finger OA, LDRT improved joint mobility and reduced inflammation, with no acute side effects.

     • Epicondylitis and plantar fasciitis showed 70–80% pain relief, aligning with OA outcomes.

   • Mechanisms: LDRT modulates endothelial cells and macrophages, polarizing macrophages to an anti-inflammatory M2 phenotype at doses of 0.3–1.0 Gy.

   • Significance: Demonstrates LDRT’s versatility across musculoskeletal conditions, with long-term benefits and minimal risks, supporting its use for tendinitis and OA.

3. Niewald et al. (2024): “ArthroRad trial: Randomized multicenter single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis—final results after 12-month follow-up”

   • Study Design: Randomized, single-blinded multicenter trial in Germany with 64 patients with painful OA, comparing LDRT (0.5 Gy or 1 Gy per fraction, total 3 Gy) to sham irradiation, with 12-month follow-up using OARSI-OMERACT criteria.

   • Key Findings:

     • At 12 months, 63–70% of LDRT patients reported significant pain relief and improved mobility compared to 30% in the sham group (p < 0.05).

     • No significant difference between 0.5 Gy and 1 Gy fractions, confirming lower doses are equally effective.

     • Minimal side effects, with no increased cancer risk observed.

   • Mechanisms: LDRT reduces leukocyte adhesion, proinflammatory cytokine production, and induces apoptosis of inflammatory cells, as evidenced by preclinical studies.

   • Significance: This RCT addresses criticisms of prior negative trials by using modern dosing and longer follow-up, providing strong evidence for LDRT’s efficacy in OA.

4. Weissmann et al. (2022): “Low-Dose Radiotherapy Leads to a Systemic Anti-Inflammatory Shift in the Pre-Clinical K/BxN Serum Transfer Model and Reduces Osteoarthritic Pain in Patients”

   • Study Design: Combined clinical and preclinical study in Germany, analyzing 196 OA patients treated with LDRT (orthovoltage, 0.5–1 Gy per fraction) and correlating with the K/BxN serum transfer mouse model using flow cytometry and ELISA.

   • Key Findings:

     • 75% of patients reported pain improvement (>20% reduction) post-LDRT, with only 1% worsening (p < 0.01).

     • Preclinical data showed LDRT induces a systemic anti-inflammatory shift, reducing proinflammatory cytokines (e.g., TNF-α) and enhancing M2 macrophage polarization.

     • Effective for ankle and foot OA, with consistent results across joint sites.

   • Mechanisms: LDRT activates Nrf2-mediated antioxidant responses and modulates immune cells, reducing inflammation at both local and systemic levels.

   • Significance: Links clinical efficacy to molecular mechanisms, addressing gaps in understanding LDRT’s action, and highlights its effectiveness for less-studied OA sites (e.g., foot).

5. Micke et al. (2013): “Efficacy of low-dose radiotherapy in painful gonarthritis: Experiences from a retrospective East German bicenter study”

   • Study Design: Retrospective analysis of 1037 patients with knee OA (gonarthritis) treated with LDRT (total 2–6 Gy, 0.5–1 Gy per fraction) between 1981–2008, with 1659 treatment series and a mail survey for long-term follow-up (106 responses).

   • Key Findings:

     • 79.3% of patients reported slight, marked, or complete pain relief within 2 months post-LDRT, with 80% showing positive responses in the mail survey.

     • Pain relief lasted up to 2 years in many cases, with no influence from age, gender, or symptom duration.

     • No significant side effects or increased cancer risk were noted.

   • Mechanisms: Anti-inflammatory effects via modulation of macrophages and cytokine pathways, consistent with modern radiobiology.

   • Significance: One of the largest historical datasets, reinforcing LDRT’s long-term efficacy and safety for knee OA, with implications for modern adoption.

Critical Analysis

• Strengths of Evidence: These studies collectively demonstrate LDRT’s efficacy in 63–90% of OA patients, with sustained pain relief (up to 2 years) and improved mobility, particularly in Germany’s standardized protocols. The minimal side effects and non-invasive nature make it appealing for elderly or refractory patients. Preclinical data elucidate mechanisms, enhancing scientific credibility.

• Limitations: Negative RCTs (e.g., Minten et al., 2018) highlight variability in response, possibly due to patient selection or short follow-up. North American skepticism persists due to limited local trials, and potential carcinogenic risks, though minimal at low doses, require long-term monitoring.

• Why Germany Succeeds: Germany’s success stems from DEGRO’s guidelines, dedicated research groups (GCG-BD), and cultural acceptance of LDRT, contrasting with North America’s focus on surgery and pharmaceuticals.

Conclusion

LDRT’s absence in the USA and Canada reflects historical abandonment, radiophobia, lack of local RCTs, and regulatory hurdles, despite robust German evidence of its efficacy for OA, tendinitis, and musculoskeletal pain. The cited papers provide compelling clinical and mechanistic support, with pain relief in 63–90% of patients and minimal risks. To bridge the gap, North America could emulate Germany’s model by forming task forces, standardizing protocols, and conducting prospective trials, as suggested by Cleveland Clinic’s initiative. Until then, LDRT remains an under-utilized but promising option.

My takeaway.

Socialized medicine has its advantages and disadvantages.

In a free market, all viable and promising treatment options are available to willing consumers based on their price, efficacy, and the efforts of the suppliers to make their product or services known to the public.

Socialized medicine has limitations. It must manage its “free health care” services by picking and choosing options without input from consumers. Rationing tax-funded medical treatments is prudent when managing a limited public purse, but why discourage free market alternatives that could help Canadians who are willing to pay out of pocket? LDRT could be offered this way in the same way that PRP way offered to me in a doctor’s office.

As a Libertarian, I have always criticized the monopoly powers for government institutions. It may serve the government to ration treatment products and services, but it eliminates the freedom of informed choice for pain sufferers.

LDRT is a safe non-pharmaceutical option. It will surely be attractive to the growing number of Canadians who have become suspicious of prescription drugs in recent years and who want access to proven alternates.

Everyone suffers pain.

It’s a universal experience which is becoming even more prevalent within Canada’s aging population.

Isn’t it appropriate for our lawmakers and regulators to make much more room for free market options within the pain management industry⁉️