Beyond Pain Control: A Novel Approach to Canine Osteoarthritis

Sponsored by Exubrion

Osteoarthritis (OA) is a chronic and progressive disease of the joint characterized by synovial inflammation, which drives the loss of articular cartilage and osteophyte formation, which both contribute to impaired joint function and pain.¹ Although OA is often associated with aging, it frequently develops in young dogs as a consequence of developmental orthopedic diseases such as elbow dysplasia and hip dysplasia. Predisposing factors such as obesity in companion dogs and repetitive activities in working dogs can increase joint wear, accelerating development of OA.²

Rethinking Osteoarthritis: More Than Just Pain

OA is a complex disease process involving cartilage, bone, and synovium. Although structural changes such as cartilage loss and osteophyte formation are hallmarks of OA, synovitis (ie, synovial inflammation) precedes radiographic evidence and clinical signs of OA and is increasingly recognized as having an important role in the pathophysiology of OA. Synoviocytes are metabolically active cells in the joint space and are involved in maintaining joint homeostasis; however, when disrupted, they can trigger an inflammatory response, leading to the activation of synovial macrophages and the release of proinflammatory cytokines, which can further disease progression and increase pain.^2,5 Targeting inflammation early can help mitigate this inflammatory cascade, delay OA progression, and alleviate pain.

Sn-117m: An Evidence-Based Therapy

Historically, limited strategies have been available for the management of OA. Lifestyle changes, including weight loss, low-impact activities (ie, walking), and at-home modifications, along with NSAIDs, have been the traditional focus.^3,4 However, radiosynoviorthesis, a therapeutic intra-articular (IA) approach in which low-energy ionizing radiation emitted by a radionuclide of tin penetrates the synovial membrane, is another management approach offering key benefits. The principle of this therapy is to reduce pain and inflammation by targeting the affected tissue while minimizing radiation exposure of healthy surrounding tissues.^5,9

Sn-117m emits low-energy particles with a precise and short penetration range, avoiding radiation exposure to nontarget tissues such as bone, cartilage, tendons, and ligaments. Sn-117m has a half-life of ≈14 days, with a duration of effect spanning several half-lives, which allows for therapeutic effects to persist for up to 1 year.^5,6,8,9

Sn-117m is administered via IA injection under sedation. The radionuclide particles are selectively phagocytized by synovial macrophages and synoviocytes, causing apoptosis of these inflammatory cells. The combination of selective uptake, short penetration range, and long-lasting therapeutic effects makes Sn-117m a safe, durable, and convenient OA therapy.^6,9

Clinical Evidence Supporting Sn-117m Use

A study evaluated the safety and intra-articular retention of Sn-117m following IA injection of both elbows in clinically normal dogs.⁹ Serial blood, urine, feces, and organ counts showed >99.1% joint retention of the Sn-117m. All dogs were deemed healthy based on physical examination, laboratory results, and radiographic evaluation and given further IA injections. Dogs were then euthanized for tissue sampling and evaluation of radioisotope retention. Scintigraphy of the major organs showed that Sn-117m remained highly localized within the joint, with no systemic adverse effects observed.⁹

An efficacy study evaluated the clinical effects of IA Sn-117m in managing naturally occurring canine grade 1 or 2 elbow OA. The study assessed IA Sn-117m by quantifying changes in peak vertical force using force plate gait analysis and canine brief pain inventory scores. Treatment resulted in improvement in both peak vertical force and canine brief pain inventory scores, providing preliminary evidence of the therapeutic benefits of elbow OA management in dogs. No adverse effects were noted on physical examination or reported by owners.⁶

Another study evaluated treatment response in dogs with confirmed grade 3 OA.⁵ This study compared the level of pain at baseline with pain at 90-day intervals for 1 year. Owners assessed pain using a pain severity score and interference score. According to owners, treatment success was shown to be >70% at all follow-ups, with mean pain severity and interference scores exceeding the predefined criteria for success. This study concluded that a single IA dose of Sn-117m can result in significant pain reduction in dogs with advanced OA for up to 1 year. The studies described demonstrate that Sn-117m is effective at providing analgesia across varying severities of OA.⁵

With Sn-117m being a radiotherapeutic, there can be questions regarding its safety and adverse effects when used repeatedly in patients. A 2021 study evaluated long-term use of Sn-117m by injecting dogs with grade 1 or 2 elbow OA in the same joint at least 12 months apart.⁷ Treatment safety was measured by evaluating joint fluid, urinalysis, CBC, and serum chemistry at baseline and 180 days posttreatment. At day 180, all laboratory parameters were within normal ranges and joint fluid analysis showed a significant reduction in monocyte percentage, suggesting an effective anti-inflammatory response. No local or systemic adverse effects were observed, confirming Sn-117m to be suitable for multidose treatment of the same joint.⁷

Radiation exposure to pet owners is not a concern with Sn-117m treatment if home care guidelines are followed. The US Nuclear Regulatory Commission evaluated the dose assessment of Sn-117m and provided guidance on how to maintain the dose below the federally established limits of 1 mSv for humans exposed to treated animals (the radiotherapy-treated human allowance is 5 mSv, 5× higher). The protocol involves owner release instructions and follow-up 1 week after discharge to assess compliance. A prospective study used dosimeters worn by owners near their treated dog to collect exposure data. The average exposure was 0.09 mSv (<1 chest radiograph¹⁰) over 1 year, and maximum results over time were ≈25% of the annual public dose limit. These results support that the protocol provided by the manufacturer meets the federally established dose limit.¹¹

Integrating Sn-117m Into Multimodal Osteoarthritis Management

Sn-117m therapy offers a valuable role in the multimodal management of OA. Sn-117m can be particularly beneficial in patients that are poor candidates for NSAIDs due to preexisting comorbidities. Importantly, Sn-117m has been shown to be disease-modifying for OA in rodent models; therefore, treatment with Sn-117m early in the disease process of OA is recommended.¹²

Patients with early synovitis but without advanced radiographic changes also make ideal candidates. Early therapeutic intervention with Sn-117m may delay progression of structural joint changes that drive progression to more advanced OA. The therapeutic effects of Sn-117m can be enhanced when combined with traditional OA management options (eg, weight loss, physical rehabilitation, NSAIDs). Treatment response can easily be monitored through physical examinations and canine brief pain inventory scoring.

Conclusion

Synovitis plays an important role in the pathophysiology of OA, triggering an immunomodulatory inflammatory response that disrupts the structural integrity of the joint before the onset of clinical signs of OA. Early recognition and therapeutic management of synovitis are essential to mitigating the inflammatory cascade, delaying OA progression, and delivering pain relief.

Sn-117m specifically targets synovial inflammation through a precise range of activity, selectively targeting synovial macrophages to address the cycle of inflammation and tissue destruction. With proven sustained efficacy and therapeutic effects lasting up to 1 year, Sn-117m is an important radiotherapeutic treatment to consider in OA patients as part of a multimodal management plan.