Low-dose radiation for osteoarthritis

Radiation oncologists in the Penn Functional Radiation Medicine program are investigating low-dose radiation therapy (LDRT) as a treatment for osteoarthritis (OA) of the hip and knee.

Used to treat osteoarthritis for more than a century in Europe, LDRT was available in the United States until the 1960s, when two intersecting factors tempered enthusiasm for the modality. The first was the publication of a series of high-profile reports detailing the risks of secondary cancers in patients treated with radiotherapy for arthritis and other benign conditions. [1,2] The second, perhaps greater factor, was the concurrent rise of NSAID therapy for OA.

Despite a decline in the US, LDRT use continued in Europe, where studies suggested its great promise as a treatment for refractory OA pain.

Clinical rationale for LDRT in OA

The most common degenerative joint disease, OA is driven by cartilage matrix degeneration and a resultant innate immune response. The latter involves a cascade of events that provokes and sustains synovial inflammation, leading to further cartilage destruction and joint instability. Pain is the principal symptom of OA, and a leading cause of related disability. As a result, resolution of pain is an objective for most therapeutic interventions for the disease, including LDRT.

The mechanisms of pain relief with LDRT are under continued investigation. It is thought that LDRT blunts inflammation by modulating innate immune cell activation, diminishing local pro-inflammatory cytokines, inducing the apoptosis of inflammatory cells, and promoting immunosuppression and tissue repair. These effects bring about a reduction in synovial inflammation and local edema and modulate the intensity of pain in the affected joint.

By comparison to other common applications for radiotherapy, LDRT has the benefits of greatly reduced dosing and an abbreviated dosing schedule. This results in a lower incidence of potential radiation-induced adverse effects. Moreover, LDRT may provide durable symptom relief without hastening joint degeneration or precluding surgical options in the future.

Clinical studies have suggested that LDRT provides symptomatic pain relief in 60% to 90% of OA patients with minimal acute side effects. [3] Current LDRT investigations suggest that the therapy is an appropriate option for medically refractory pain in patients with OA who are >40 years of age. [4] The standard course of LDRT to arthritic joints is 3 Gy administered over six visits at increments of 0.5 Gy, which is 1/20th of the dose used to treat lung cancer.

Case report

Mrs. M, a 76-year-old woman, was referred to Penn Radiation Oncology for evaluation of her knee osteoarthritis. A breast cancer survivor, Mrs. M was taking daily anastrozole, a medication indicated for the prevention of disease recurrence in postmenopausal women with hormone receptor-positive breast cancer. Anastrozole dramatically lowers endogenous estrogen levels and is linked to severe arthralgia and osteoporosis. In addition, Mrs. M had a history of chronic bilateral knee osteoarthritis.

Despite increasing pain and worsening issues with ambulation and the activities of daily living, Mrs. M had no interest in knee replacement surgery or steroid injections and welcomed a non-invasive alternative. After a consultation with John P. Plastaras, MD, PhD, to review the benefits and risks of LDRT, including the possibility of transient joint discomfort and in-field cancer development, Mrs. M agreed to a course of treatment.

At the conclusion of baseline imaging at Penn Medicine, Mrs. M received the standard course of 3 Gy administered over six visits (twice a week for three weeks) at increments of 0.5 Gy. Radiotherapy was applied with an anterior-posterior/posterior-anterior (AP/PA) beam approach to both the left and right knees, resulting in an even, uniform dose distribution at the knee (Figure 1).

Mrs. M reported early improvement in her arthritis pain and functional improvement when seen during her radiation treatment course. She had complete resolution of her pain when seen three months following the conclusion of treatment. In addition, she noted significant improvement in her ability to squat and climb stairs.

LDRT at Penn Medicine

LDRT is available as a standard of care therapy at the Penn Functional Radiation Medicine Program of Penn Presbyterian Medical Center. The Program team includes John P. Plastaras, MD, PhD, Michelle Iocolano, MD, Eva Berlin, MD, and Logan Barnes, PA-C.

Treatments are offered to select patients with medically-refractory OA joint pain in the extremities, excluding the spine.

Referrals and consultations

To contact a specialist at the Penn Functional Radiation Medicine Program, please call 215-614-6091.

References

1. Cannon B, Randolph JG, Murray JE. Malignant irradiation for benign conditions. N Engl J Med. 1959;260:197-202.
2. Brown W, Doll R. Mortality from cancer and other causes after radiotherapy for ankylosing spondylitis. Br Med J. 1965;2:1327–1332.
3. Donaubauer A-J, Zhou J-G, Ott OJ, et al. Low dose radiation therapy, particularly with 0.5 Gy, improves pain in degenerative joint disease of the fingers: Results of a retrospective analysis. Int J Mol Sci. 2020; 21:E5854.
4. Schlamann A, Yu JB, Ruhle A. Low-dose radiotherapy for osteoarthritis: current evidence, practical recommendations and future perspectives. Semin Radiat Oncol. 2026;36:39-47.