Radiation Therapy in Osteoarthritis Management

Radiation oncology became recognized as a specialty for veterinarians in 1994 and has become a crucial modality in the cancer treatment of companion animals. While rarely used as a sole modality in cancer treatment, radiation therapy (or radiotherapy) is widely used in the treatment of many different tumor types. When radiation therapy is used in this setting, patients often receive a higher total dose of radiation, with the goal of inducing enough DNA damage to lead to cell death. However, low-dose radiation therapy (LDRT) is the modality used when the purpose of radiotherapy is anti-inflammatory (BOX 1).

Using radiotherapy for anti-inflammatory benefits is not a new concept, particularly in human medicine, where efficacy has been clinically documented for several decades.² There remains a lack of controlled studies and established protocols, making the use of LDRT in the United States inconsistent. However, more than 85% of providers in Central European countries utilize LDRT for benign conditions—particularly in Germany, where more than one-third of radiation therapy cases are for benign diseases.³ The successes seen in human medicine eventually led to veterinarians investigating radiotherapy for non-neoplastic conditions as well. Veterinary medicine has very few published studies evaluating radiotherapy in this setting. However, several universities are evaluating its use in conditions such as chronic rhinitis, feline idiopathic cystitis, and osteoarthritis (OA).

What Is OA?

OA is a chronic, progressive condition that affects both dogs and cats. It is associated with the degradation of articular cartilage and is often accompanied by synovial inflammation, periarticular osteophytosis, and alterations in subchondral bone metabolism.⁴ This can lead to substantial pain in companion animals, and without adequate analgesia, a decrease in quality of life is expected. OA can be primary or secondary, with secondary being the most common form in dogs. Primary OA is not well understood and is largely idiopathic, although aging and obesity seem to predispose patients to this condition. Secondary OA is the result of previous trauma or ailments such as historical fractures, hip dysplasia, elbow dysplasia, or cranial cruciate ligament disease.

In the canine patient, clinical signs often present as lameness, stiffness, decreased energy levels, difficult ambulation (particularly when rising, using stairs, or jumping), and muscle wasting. It is estimated that 20% of dogs over 1 year of age have OA.⁵ This is a surprising statistic, as many owners and veterinary professionals consider OA to be a condition associated with old age. While it is known that aging increases the likelihood of developing OA, studies have also shown that many young adult dogs will be affected by OA, and the condition may be subclinical.⁵

In the feline patient, clinical signs are more difficult to recognize, especially given the fact that cats hide pain. This has led to OA being widely underdiagnosed in cats. Although some cats may present with lameness or gait changes, the majority of owners report a reluctance in jumping, a decreased energy level, or behavioral changes. One study found the most common clinical signs associated with OA in cats to be decreased mobility, less grooming, and increased elimination directly over the edge of the litterbox.⁶ The same study suggests that roughly 61% of cats are afflicted by OA, increasing to 82% in cats older than 14 years of age.⁶

Why Do We Need Alternative Therapies for OA?

Because of the high prevalence of OA, most veterinary professionals are quite familiar with the therapeutic options for this condition. Analgesics, nutraceuticals, and weight management are very common therapies offered by primary veterinarians. Analgesics are often combined to target multiple stages of the pain pathway (FIGURE 1 AND TABLE 1), with varying results and side effects. Some veterinarians and specialty practices may also offer therapies such as intra-articular injections, physical rehabilitation, laser therapy, acupuncture, or hydrotherapy. The efficacy of these treatment options is subjective, and all are chronic in nature—financially impacting pet owners for the remainder of their pet’s life. In some cases, surgical intervention may also be recommended to provide pain relief.

Figure 1. Illustration of an osteoarthritic knee joint showing the 4 main stages of the pain pathway in osteoarthritis and the targets of certain drugs. Transduction is the conversion of a nociceptive stimulus into electrical impulse. Transmission is the electrical impulse transmitted from peripheral sensory nerves to the central nervous system (CNS). Modulation is how the nociceptive stimulus is processed by the CNS and includes the endogenous opioid system, as well as ascending input and descending inhibitory pathways. Perception is how the brain (particularly the somatosensory cortex) interprets nociceptive inputs, resulting in a conscious perception of pain.7 Low-dose radiation therapy (not represented in this illustration) interferes at a cellular level pretransduction, resulting in a cascade that promotes an anti-inflammatory environment. Courtesy Kip Carter.
Anti-NGF mAbs = anti–nerve growth factor monoclonal antibodies; NMDA = N-methyl-d-aspartate; NSAIDs = nonsteroidal anti-inflammatory drugs

While there is no cure for OA, better long-term management options would have a profound impact on companion animals and pet owners alike.

How Does LDRT Work?

The radiobiological mechanisms in LDRT are not completely understood. However, anti-inflammatory effects have been found in various in vitro experiments, in vivo studies, and clinical studies, supporting its clinical efficacy.

When high-dose radiation therapy is used in cancer treatment, proinflammatory cytokines are produced, causing inflammation in the irradiated tissues and leading to the side effects commonly seen during radiotherapy. Interestingly, LDRT has a paradoxical effect in which the inflammatory response is modulated by acting upon endothelial cells, mononuclear cells, macrophages, and granulocytes. Additionally, LDRT lowers the production of cytokines, nitric oxide, and reactive oxygen species, which would otherwise contribute to inflammation.^8,9

How Effective Is LDRT for Inflammation?

There have been numerous in vivo studies performed since the 1930s on animal models, specifically rabbits and rats. In the majority of these studies, investigators would induce acute arthritis and follow with varying doses of radiation to evaluate the response. These studies found that LDRT reduced inflammatory proliferation of synovial cover cells, reduced the synthesis of synovial fluid and swelling, and reduced cartilage degradation.² These early studies prompted the investigation of LDRT in human patients, with multiple studies demonstrating long-term efficacy in the treatment of degenerative bone and inflammatory diseases, such as OA.⁷

Although scarce, several studies have evaluated the use of LDRT in canine and feline patients. In dogs, published studies delivered a total dose of 6 to 10 Gray (Gy) over 1 to 3 fractions of radiation.^9,10 The most convincing of the studies found that improvement was observed in 92% of dogs, with a median benefit duration of 356 days following the first treatment and 418 days after the second treatment. ⁹ This study also recorded no side effects related to radiotherapy. Only 1 published study has evaluated the use of LDRT in multiple feline patients. This case study revealed that of 3 cats diagnosed with osteochondrodysplasia, all 3 experienced long-term (59- to 72-month) pain control following LDRT.¹¹

In the author’s experience, lower radiation doses per fraction (≤ 0.75 Gy) may also be considered to further spare healthy cells while still secreting anti-inflammatory cytokines, which theoretically creates the optimal setting of minimizing cell death while benefiting the patient.

At this time, there is not enough data to determine if LDRT is more effective for early stages of OA versus the late or end stage. Translational data from human studies would potentially support the theory that LDRT would be more effective on earlier stages of OA, while higher doses of radiation may be considered for more debilitating stages. More research is needed to understand the intricacies of LDRT and provide situational understanding.

How Is LDRT Administered?

LDRT is administered using a radiotherapy unit called a linear accelerator. These units are becoming increasingly common at specialty centers offering radiation therapy due to their greater flexibility in treating both deep and superficial tumors. A veterinary radiation oncologist is responsible for the planning and administration of radiation therapy. As of December 2023, the AVMA reported that there are 139 veterinary radiation oncologists boarded in the United States, leading to radiation therapy options in more than 30 states.¹² This number is expected to grow each year, making radiation therapy increasingly available for pet owners. It is important to investigate whether a referral center is offering LDRT for benign conditions before referral, as this remains a novel therapy.

To adequately spare normal tissues from irradiation, patients must be immobilized during treatment. Animal patients are generally anesthetized during radiotherapy for this reason. The patient may be placed in dorsal, sternal, or lateral recumbency, and care should be taken to avoid causing pain during positioning. For advanced OA cases, owners should be made aware that their pet may experience increased pain initially due to patient positioning. The length of anesthesia will vary depending on the number of joints being irradiated, with 20 minutes being the mean anesthesia time in 1 study.⁹ The benefits of radiation have been largely apparent at 2 to 3 weeks post-treatment, with some patients experiencing enough success to decrease or discontinue other analgesic therapies.

More studies are needed to fully evaluate the efficacy and side effects associated with LDRT and establish more standardized protocols for anti-inflammatory purposes. However, based on previous and emerging data, LDRT should be considered when managing OA or other inflammatory conditions that are otherwise difficult to manage.

How Can I Inform Owners About This Treatment Modality?

As with any treatment option, being transparent with pet owners when discussing disease management is important. LDRT can be described as a novel therapy with plenty of data supporting its safety and efficacy in human medicine, but with few to no standard protocols in veterinary medicine. LDRT can improve quality of life in OA patients and potentially reduce the need for oral analgesics.

The cost for LDRT is highly variable and depends on the physical location of the facility, the number of joints irradiated, and the number of fractions given. Pet owners should expect to pay $1500 or more and be willing to travel to sites that offer this therapy.

A brief online search found that PetCure Oncology offers LDRT for various benign conditions at multiple locations across the United States.¹³ Other specialty practices and teaching hospitals likely offer LDRT, but it was not highly advertised at this time.