Old Dogs, New Tricks: Managing Osteoarthritis in Pets

Osteoarthritis (OA) is a chronic disease of joints marked by inflammation and cartilage breakdown and is a common problem in aging pets. It is often called a “wear and tear” condition because it's linked to joint use and stress. The clinical signs include joint pain and swelling during or after movement, stiffness, especially in the morning or after periods of inactivity, and reduced flexibility. Because the onset is often slow and insidious, owners may not realize their pets are suffering from OA, mistakenly believing they are simply “getting old.” Routine veterinary examinations can help detect OA at its earliest stages when it is most responsive to treatment. While it can’t be prevented, there are a number of ways that owners can help mitigate the impact of OA as their pets grow older.

Move More
While it may seem counterintuitive, movement is some of the best medicine for arthritis. Studies in both humans and animals have shown that exercise can reduce many of the clinical signs of OA. Physical activity, along with an appropriate diet, can also help prevent obesity in pets. Excess weight adds to the load the joints must carry, accelerating the development of arthritis and aggravating its clinical signs. Depending on the age and general health of the pet, owners may want to consult their veterinarian before embarking on an exercise regimen, but most pets will benefit from more physical activity.

Make Your Pet More Comfortable
Veterinarians have a plethora of therapeutic options they can prescribe to treat the clinical signs of OA in dogs. Of these, non-steroidal anti-inflammatory drugs (NSAIDs) are the most common. Similar to drugs like ibuprofen and aspirin for humans, they work by inhibiting a cyclo-oxygenase (COX-2) enzyme that is critical for the production of inflammatory mediators. There are a number of different NSAIDs approved by the Food and Drug Administration (FDA) for use in dogs with OA, including carprofen, deracoxib, and firocoxib. They are administered orally, once or twice a day, and many have formulations that are palatable to the dog. In general, NSAIDs are very effective and inexpensive.  That said, they are associated with adverse events (AEs) which include gastrointestinal irritation and ulceration, renal and kidney damage, and platelet dysfunction leading to prolonged bleeding times. While these AEs are not common, chronic use of NSAIDs, which is typically required for treatment of OA, increases the risk of their occurrence. These AEs occur because most NSAIDs inhibit not only COX-2, but a structurally similar enzyme COX-1. The COX-1 enzyme is important in many normal physiological processes including protection of the gastrointestinal mucosa, maintaining renal blood flow, and regulating platelet function. Newer NSAIDs, such as firocoxib, are highly selective for the COX-2 enzyme and generally have improved safety profiles over older non-selective agents, but they are also more expensive.

Grapiprant is an anti-inflammatory agent FDA-approved for use in dogs with OA. It does not inhibit the COX enzyme system but rather produces its anti-inflammatory effects by blocking the binding of prostaglandin, an important mediator in the inflammatory cascade.  Its unique mechanism of action results in an excellent safety profile. It is administered orally, once a day, and there are a number of palatable formulations available at reasonable prices.

Unlike in dogs, NSAIDs are not a great option for the treatment of OA in cats. Meloxicam and robenacoxib are the only NSAIDs approved by the FDA for use in cats, and neither is recommended for chronic administration. NSAIDs are effective at decreasing the clinical signs of OA in cats, but this species seems to be exquisitely sensitive to the negative effects of these agents so AEs occur fairly commonly. Cats should be carefully screened before starting therapy and frequently monitored during treatment with NSAIDs. There are other analgesics that can be used in cats to control pain, including gabapentin and pregabalin, and owners should discuss their use with their veterinarian. Fortunately, several new therapeutic modalities for the treatment of OA in cats are either in development or already available as discussed below.

Owners should never give their pets NSAIDs approved for use in humans, such as ibuprofen or naproxen, unless directed by their veterinarian. Dogs, and particularly cats, don’t metabolize these drugs like humans and therefore toxic reactions are a significant risk.

New Tricks for Old Dogs, and Old Cats
One of more recent advances in the treatment of OA in cats and dogs has been the development of monoclonal antibodies (mAbs) targeting nerve growth factor (NGF), a key mediator of pain. Frunevetmab (Solensia, Zoetis) and bedinvetmab (Librela, Zoetis) are FDA-approved for the control of OA pain in cats and dogs, respectively. When a monoclonal antibody is developed for therapeutic use, it must be engineered to match the immunoglobulin structure of the target species—a process called caninization for dogs and felinization for cats. This process is critical because if a cat or dog was administered a human antibody, or an antibody from any other species for that matter, their immune system would recognize it as foreign and mount an anti-drug antibody response. The result would be a neutralization of the drug and potentially a hypersensitivity reaction in the pet. By engineering the antibody framework regions to match the target species, while retaining the specific antigen-binding regions, immunogenicity is minimized and the drug's efficacy and duration of action are preserved. Both frunevetmab and bedinvetmab are administered monthly by a subcutaneous injection. Dog owners need to weigh the convenience of once-a-month dosing of mABs by a vet versus the daily dosing of NSAID at home.  In addition, while these therapies are more expensive than NSAIDs, they are extremely effective in both dogs and cats.

The safety profiles of frunevetmab and bedinvetmab are generally good. Their highly targeted mechanism of action, binding and neutralizing NGF, blocks a critical pathway in chronic pain without broad systemic effects. Recently, however, there have been reports of adverse neurological events, including seizures, ataxia, muscle weakness and paralysis, associated with their use in dogs and to a lesser extent, cats. Because NGF plays a role in neuronal survival, maintenance, and function, blocking it with an anti-NGF antibody could theoretically have neurological consequences. How common these AEs are in the general pet population and whether they are reversible if they occur, is still being determined.

Make Everything Old, New Again: Regenerative Medicine
Regenerative medicine is an exciting approach focused on repairing, replacing, or regenerating damaged or diseased tissues and organs. Rather than simply managing the clinical signs, regenerative medicine aims to address the underlying structural and biological deficits that drive disease. Many of the current modalities, such as platelet-rich plasma (PRP), are administered directly into an affected joint, and can be very effective. However, because aging-associated OA generally affects multiple joints, intra-articular therapies are less useful. However, one of our portfolio companies Gallant Therapeutics is evaluating the effects of mesenchymal stem cells administered intravenously to dogs and cats suffering from OA. Preliminary results are extremely encouraging, and, as discussed in more detail in a previous Notes on Animal Health, through pioneering companies like Gallant, the promise of stem cell therapies may finally be delivered.

Support Joint Health
Many pet owners purchase joint health supplements in the belief that they can prevent or slow the development of OA in their pets. While there is no evidence that any of these products can actually alter the course of OA, some ingredients may reduce its clinical signs with few if any negative effects. Other ingredients produce few or no demonstrable therapeutic effects and are therefore likely a waste of money, while a few ingredients may actually be toxic to pets. It’s important that pet owners know the difference.

Dietary supplements are advertised as adding nutrients or other beneficial substances to you or your pet’s diet. The FDA regulates products meant for human consumption under the Dietary Supplement Health and Education Act (DSHEA) of 1994, but there is no DSHEA equivalent legislation for products used in animals. Therefore, although the FDA still regulates them as food products, pet dietary supplements undergo much less scrutiny than products meant for human consumption. Because supplements have not undergone any form of FDA review, they cannot claim to prevent, treat or cure a disease or condition including OA and therefore, most are labeled as products that “promote” or “support” some organ or tissue, such as “supporting joint health.”

Omega-3 Fatty Acids (O3FA)
O3FA have been well-studied in humans and linked to a range of benefits including reducing the signs of OA. Although there are fewer studies in dogs and cats with OA, most find positive effects and importantly few AEs. Numerous studies have shown that O3FA modulate a diverse array of inflammatory pathways leading to a reduction in inflammation throughout the body, including the joints.

Many joint supplements contain fish oil, krill oil or cod liver oil, all of which are good sources of two of the most important 3OFAs, Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA). In contrast, flaxseed oil, which is also used in some supplements, only contains the 3OFA alpha-linolenic acid (ALA). Although some species can convert ALA to EPA and DHA, dogs and cats do not do so efficiently, and therefore in terms of joint support, fish and marine oils are likely superior to flaxseed oil.  However, fish oils can be contaminated with heavy metals, PCBs, and dioxins, so owners should look for products that carry third party certifications, such as the National Animal Supplement Council (NASC), that ensure purity of the product. O3FA are also highly susceptible to oxidative rancidity and therefore products containing antioxidants, such as Vitamin E, may be more stable for longer periods of time.

Joint supplements containing extracts of Green lipped mussel (Perna canaliculus), a shellfish native to New Zealand, have recently become very popular. Green lipped mussel extracts contain not only DHA and EPA, but eicosatetraenoic acid (ETA), a 3OFA that is not found in fish oils and which has unique anti-inflammatory properties. Most, but not all, studies show positive effects of Green lipped mussel extracts on the clinical signs of OA in dogs, cats, and humans.

Components of Healthy Cartilage 
Supplements meant to promote joint health often contain substances found in normal healthy joints including glucosamine, chondroitin, and collagen. It has been proposed that supplementing these building blocks of healthy cartilage can decrease inflammation and increase the rate of cartilage repair. Unfortunately, the evidence supporting the effectiveness of most of these ingredients is sparce. For example, a recent metanalysis of the effects of glucosamine and pentosan polysulfate in dogs suffering from OA concluded that the evidence of their therapeutic effect was relatively weak. Another review concluded that the potential benefits of glucosamine and chondroitin use in dogs with OA was inconclusive. The evidence for the use of collagen is better, with one recent review and a well-controlled clinical trial in dogs concluding overall positive effects in animals suffering from OA. These types of ingredients appear to be safe, but pet owners should be aware that, other than collagen, they are not likely to contribute much to the effectiveness of any joint supplement.

Herbal Remedies & Tradional Chinese Medicine (TCM)
Other common ingredients in joint supplements include various herbal or botanical extracts and actives used in TCM preparations. There is limited evidence that several botanicals including turmeric, Ashwagandha, Boswellia serrata, and willow bark, may be mildly effective in the treatment of OA. Interestingly, many of these natural remedies produce their effects through the same pathways as conventional NSAIDs, that of inhibiting the COX enzyme system. In a similar manner, while many components of TCM have not been studied using Western-style research protocols, a few have and they also appear to work through well-described inflammatory pathways. Many of these substances have only been studied in rodents or humans. Therefore, their efficacy in dogs and cats suffering from OA has not been determined. In addition, pet owners need to be aware that some substances safe for use in humans and rodents are toxic to dogs and cats. Owners should use caution when choosing products with unusual or untested ingredients and may wish to consult with their veterinarian before using them.

In summary, other than O3FA and collagen, there is limited evidence to support the use of most joint health supplements in dogs and cats suffering from OA. While most of these products are likely not harmful to pets, they may be unnecessarily harmful to the owner’s wallet.

End Game
OA is a common, chronic inflammatory condition that plagues many pets as they age. While there is currently no way to prevent it, owners can promote healthy joints by giving their pets plenty of exercise and a healthy diet rich in O3FAs. When OA begins to affect their pet more significantly, there are many effective and safe therapies that can help mitigate its clinical signs. Working with their veterinarian, pet owners can determine which therapy is the best option for their pet. These approaches can help to give owners more happy and healthy years with their pet.

– Cindy Cole, DVM, PhD, DACVCP




1/ Finicky Cats
Many owners have felt the frustration of buying food that their cats seem to like, only to see them turn up their noses at it a few days later. A recent study from Iwate University, Japan found that changing the smell of the food, even slightly, may entice finicky cats to eat. Using different toppers on the same diet or offering different varieties of prepared diets and combining wet and dry formulations may keep cats interested in eating. However, owners need to keep in mind that obesity is a problem for many cats, so they need to be careful they don’t solve one problem only to create another.

2/ Can Your Dog Carry a Tune?
Most of us have watched cute videos of dogs howling along to music. Researchers wanted to know if, like people, dogs change their tune depending on the music. It turns out that at least one dog breed does. The study found that Samoyeds, an ancient arctic breed, significantly changed their mean vocal pitch when howling with music that had been shifted up versus down in frequency. In the same study another ancient breed, Shiba Inus appeared tone deaf and did not modulate their howl. The findings might offer some insights into the origins of human music. It has been argued that singing evolved from the fine motor control that came with speech, but the fact that dogs can also control pitch without any other forms of vocal learning suggests that language would not necessarily be a mandatory precursor to singing.

3/ A Roman Horse Cemetery
Archaeologists have unearthed a very rare Roman-era horse cemetery in Germany containing the skeletons of over a hundred horses. They were part of an unusually large second-century AD Roman military unit with over 5,000 men and 700 horses. Whenever a cavalry horse died, it would be buried about 400m away from the equestrian castle and civil settlement. One horse was buried with two jugs and a small oil lamp, typical grave goods for humans, placed in the crook of a forelimb as a farewell.

4/ Dogs Are Like Toddlers
The results of a recent study found that some dogs learn words through overhearing just like, or even better than, 1.5-year-old children. Not all dogs have this skill, but those described as “Gifted Word Learners”, possess an extensive vocabulary of object labels, and can learn new labels by overhearing their owners’ interactions.

5/ Landing on Your Feet
Cats often impress us with their amazing ability to land on their feet when falling from height. The results of a recent study give us an insight into how they do this. The study found that compared to many other species, the cat’s thoracic spine is much more flexible than its lumbar region. This increased flexibility may allow the cat to easily and rapidly orientate that upper body, while the stiffer lumber section follows a bit behind, perhaps preventing the cat from over correcting. While other factors may be involved, these findings further cement the uniqueness of felines.

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