Does It Work in Dogs? Evaluating an Effective Treatment in Humans for Canine OA

In the August issue of the American Journal of Veterinary Research, you can find the first clinical study that directly compares the effects of intra-articular polynucleotide and hyaluronic acid injections on small breed dogs with osteoarthritis (OA). In this multicenter, comparative, randomized, blinded, clinical study, 34 dogs weighing less than 15 kg with hindlimb OA received 2 intra-articular injections of either polynucleotide or hyaluronic acid over a 2-week interval, then were monitored for 12 weeks following injection. Human clinical studies have suggested that intra-articular polynucleotides provide better pain relief and functional improvement than intra-articular hyaluronic acid. Polynucleotides, derived from purified salmon gonad DNA, provide longer viscosupplementation as well as anti-inflammatory, regenerative, and chondroprotective effects while also suppressing proinflammatory cytokines—ultimately, encouraging cartilage protection and repair.

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Dr. Byung-Jae Kang, one of the authors of this study, is an associate professor of small animal surgery (orthopedics and neurosurgery) at Seoul National University College of Veterinary Medicine. He answers our questions below to help us better understand the results and promising future treatment of intra-articular polynucleotides.

For this study, treatment response was measured by clinical metrology instruments, indicated by scores for the Canine Orthopedic Index (4 sections: stiffness, function, gait, and quality of life) and Canine Brief Pain Inventory (2 sections: pain severity score and pain interference score). Did these parameters make it easier to evaluate treatment response?

Dr. Kang: Yes. The COI and CBPI are well-validated clinical metrology instruments that allow us to quantify pain and functional impairment from the owner’s perspective. While radiographs or gait analysis can provide objective data, they are often impractical in daily veterinary practice. These instruments, on the other hand, are easy to use and reflect real-life functional improvement as observed by the owner. They were therefore very useful in capturing the treatment response in this study.

Consistent with human clinical outcomes, the dogs that received polynucleotides showed a quicker, better, and more sustained response to treatment than the dogs that received hyaluronic acid. Did this, or any finding, surprise you?

Dr. Kang: We expected some benefit based on prior human clinical studies, which suggested that intra-articular polynucleotides may provide superior outcomes compared with hyaluronic acid. However, since this was the first direct comparison in dogs, it was encouraging to see clear and consistent results. The improvements in stiffness and pain interference scores, in particular, were notable and clinically meaningful.

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Have the results of this study changed your clinical recommendations for small dogs with OA?

Dr. Kang: Yes. Hyaluronic acid has been widely used as the standard intra-articular therapy, but our findings indicate that polynucleotides may provide earlier, greater, and longer-lasting benefits. Based on this evidence, I would consider polynucleotides as a promising and potentially superior treatment option for small breed dogs with OA.

Are you pursuing any future studies that evaluate the effectiveness of intra-articular polynucleotides? If not, do you know of any ongoing or future studies?

Dr. Kang: Yes. This study had a 12-week follow-up period, so we need longer term data to evaluate durability of response and to establish optimal dosing schedules. We are planning follow-up studies that will include larger populations, different breeds, and longer evaluation periods. There is also interest in exploring additional orthopedic indications beyond OA.

In addition, we are investigating whether intra-articular polynucleotide injections may influence recovery speed or recovery quality in dogs undergoing TPLO surgery. In preliminary work, a single injection immediately after surgery did not produce meaningful results. Therefore, we are now following up on cases where an additional injection was administered 2 weeks postoperatively. If these ongoing studies yield significant findings, we look forward to reporting the results in the future.

What should general practitioners know about intra-articular polynucleotides as a potential future treatment option for OA?

Dr. Kang: Polynucleotides are more than just a viscosupplement. They combine viscoelastic support with anti-inflammatory, chondroprotective, and regenerative effects. This means they not only improve pain and function but may also contribute to healthier joint homeostasis. In our study, adverse events were minimal and transient, suggesting that the treatment is generally safe and well-tolerated.

Editor’s Note: This article is an excerpt from the Research Wrapped monthly newsletter. Subscribe here for free.

Is there anything you would like our readers to know that has not been mentioned?

Dr. Kang: This was the first clinical trial to directly compare polynucleotides with hyaluronic acid in dogs. The fact that polynucleotides demonstrated faster, greater, and more sustained improvements is a meaningful step forward. For veterinarians, it provides a new tool for managing OA. For patients and their owners, it offers hope for improved comfort and quality of life.

It is also worth noting that in the United States and Europe, the intra-articular options available in veterinary medicine beyond hyaluronic acid are mostly limited to corticosteroids, platelet-rich plasma (PRP), and stem cells. Corticosteroids can raise safety concerns due to adverse effects. PRP requires substantial blood collection, specialized separation kits, and centrifugation, which makes it inconvenient for routine clinical use. Stem cells are costly and often not readily available at the time of need in general practice. As a result, intra-articular therapies have not been widely adopted in veterinary medicine.

By contrast, in human medicine in Korea, polynucleotides are already being widely used as an alternative to hyaluronic acid for the management of knee osteoarthritis with an accumulating body of supporting evidence. Demonstrating similarly positive outcomes in dogs is encouraging because it means veterinarians may soon have access to a practical, evidence-based, and multimodal therapy option to improve the management of canine OA.

The Study

Intra-articular injections of polynucleotides show promise in improving clinical outcomes compared to hyaluronic acid in small-breed dogs with osteoarthritis.

Lee CL, Kim Y, Kim JI, et al. Am J Vet Res. doi:10.2460/ajvr.25.07.0243