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What are the latest treatments for the management of canine arthritis?
Arthritis is a progressive, degenerative disease. Left untreated, it can become a severe crippling condition, causing significant disability and chronic pain. In fact, end-stage arthritis is a common reason for euthanasia, especially in elderly, obese large breed dogs who can no longer move without pain or who often can no longer even stand.
Early detection and interventions are imperative for slowing down the progression of the disease and prolonging quality of life. Thankfully, over the past decade, scientists have developed a greater understanding of the biology of arthritis, and this had led to new recent advances in treatment options, such as the newly released anti-NGF monoclonal antibody.
Arthritis is a progressive inflammatory disease
Currently, there is no cure for arthritis. Instead, treatments are aimed at slowing disease progression and reducing pain, to maintain mobility and quality of life for as long as possible.
Central to managing arthritis is understanding that it is a progressive inflammatory disease. In arthritis, untreated chronic inflammation leads to progressive joint destruction and significant pain. Successful arthritis management means stopping or slowing the inflammation and reducing pain sensitisation.
#1. Progressive destruction:
Inflammation is the body’s natural mechanism for repairing damage. Whilst it is an essential function in the short-term, untreated persistent inflammation causes bystander damage to the surrounding healthy tissues. This new damage triggers more inflammation, which causes further destruction, creating an ongoing amplification cycle of chronic inflammation, damage, swelling, and pain. With arthritis, what start as inflammation in one area gradually progresses to involve damage to the whole joint.
2. Pain sensitisation:
2. Pain sensitisation:
Pain is a significant consequence of arthritis. It is also incredibly complex. There are two main ways in which pain is initiated:
%20compared%20to%20a%20joint%20showing%20severe%20cartilage%20damage%20%20(right).jpg) |
| A healthy joint (left) compared to a joint showing severe cartilage damage and arthritis in dogs (right) (1) |
2. Damage to the nerves around the joint causes neuropathic pain. Both types of signals begin at local nerve endings around the joint and travel up the nerves through the spinal cord to the brain where it registers the pain.
Inflammatory pain may feel like an ache, stabbing, or throbbing.
Neuropathic pain may feel like burning, prickling, stabbing, pins and needles, or an electric shock. Our understanding of pain in arthritis has significantly progressed. We now understand that chronic inflammation not only initiates pain, but it can actually change the way the nerves function and process pain.
It can make the nerves more sensitive to receiving pain signals, amplifying and prolonging the pain that arthritic dogs experience. As the nerves become more sensitised, the pain may become less responsive to medications that may have previously worked.
Early identification and management is crucial to achieving the best outcomes
Given what we now know about the progressive and amplifying nature of both the inflammatory damage as well as the pain in arthritis, it highlights how important it is to identify, manage, and treat arthritis early.
Early identification and management is crucial to achieving the best outcomes
Given what we now know about the progressive and amplifying nature of both the inflammatory damage as well as the pain in arthritis, it highlights how important it is to identify, manage, and treat arthritis early.
Early signs of arthritis can include sitting with one leg out to the side, difficulty rising or laying down, reluctance to jump, and trouble with stairs.
Later changes can include limping, reduced movement of joints, loss of muscle mass, and joint thickening. A veterinarian can help identify symptoms.
The keys to successful arthritis management are:
1. Reducing the risk factors
2. Early identification and management
3. Treating inflammatory flare-ups promptly to reduce further joint damage
4. Controlling pain and preventing pain sensitisation
The primary prevention and management options:
The keys to successful arthritis management are:
1. Reducing the risk factors
2. Early identification and management
3. Treating inflammatory flare-ups promptly to reduce further joint damage
4. Controlling pain and preventing pain sensitisation
The primary prevention and management options:
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| Weight loss is an important part of dog arthritis treatment as it relieves stress on arthritic joints |
1. Weight management remains the mainstay for preventing and managing arthritis. Obesity is a very high-risk factor for the development and progression of arthritis. It is not merely that the increased body weight creates more wear and tear on joints.
Fat cells release inflammatory proteins that cause body-wide low-grade inflammation, including within joints. This can both cause and worsen arthritis. Plus, for dogs that are already struggling to walk on arthritic joints, the extra bulk makes it even harder to stand and walk, making important regular exercise difficult (see below).
Thus, achieving and maintaining an optimal body weight is a must. Prescription weight loss diets, like Hills Metabolic plus Mobility, may help. Talk to your veterinarian about achieving and maintaining ideal body weight.
2. Regular exercise is vital.
Regular, gentle exercise maintains joint mobility, keeps the joints lubricated, and maintains cartilage, muscle, and bone strength. On the other hand, inactivity leads to joint stiffening, a decline in joint health, muscle weakness, and increased pain.
Even in dogs with advanced arthritis, regular, gentle, low-impact walks or swimming are important. This can be combined with physiotherapy and passive range of motion exercises (bending and stretching the limbs around each joint for your dog), especially in dogs which struggle to move themselves.
3. Omega-3 fatty acids have been shown to be very effective at reducing inflammation and reducing the progression and symptoms of arthritis.
3. Omega-3 fatty acids have been shown to be very effective at reducing inflammation and reducing the progression and symptoms of arthritis.
However, the dose needs to be adequate. The important omega-3 fatty acids are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The minimum recommended dose is 100 mg/kg of DHA or EPA daily.
Many foods, even those claiming to be high in omega-3 fatty acids, don’t reach the minimum recommended dose. Fish and marine based oils (like salmon, tuna, and green lipped mussel) provide the highest concentrations of EPA and DHA. Plant-based ALA omega-3 fatty acids are not efficiently processed by dogs’ bodies to be of help. If choosing a food which claims to be rich in omega-3 fatty acids, check that it is rich in DHA and EPA, and not merely rich in plant-based ALA.
4. Joint injury prevention strategies are important. Any injury to a joint can initiate or promote progression of arthritis. Whilst it is important to let dogs be dogs, it can be wise to avoid high impact activities, like ball or stick throwing that causes dogs to jump and twist and land from a height.
4. Joint injury prevention strategies are important. Any injury to a joint can initiate or promote progression of arthritis. Whilst it is important to let dogs be dogs, it can be wise to avoid high impact activities, like ball or stick throwing that causes dogs to jump and twist and land from a height.
This is especially so for higher risk groups, such as dogs that are obese, or have a long spine, short stocky twisted legs, hip or elbow development issues, dislocating kneecaps, dogs with previous knee injuries, older dogs, or those already with arthritis. Child gates, ramps, steps, and carpets may all help.
5. When a joint injury or flare-up in arthritis occurs, it is important to treat it promptly. Prompt recognition and treatment of active inflammation is necessary to settle the inflammation and pain quickly before they both amplify and become chronic.
A) Non-steroidal anti-inflammatory drugs (NSAIDs) are currently still the cornerstone medication for arthritis flare-ups. Common examples include meloxicam, carprofen, and robenacoxib, often given as a daily tablet or liquid.
5. When a joint injury or flare-up in arthritis occurs, it is important to treat it promptly. Prompt recognition and treatment of active inflammation is necessary to settle the inflammation and pain quickly before they both amplify and become chronic.
A) Non-steroidal anti-inflammatory drugs (NSAIDs) are currently still the cornerstone medication for arthritis flare-ups. Common examples include meloxicam, carprofen, and robenacoxib, often given as a daily tablet or liquid.
Please Note: Never give the human medication forms to dogs. NSAIDs suppress inflammation, thus reducing the cascade of further joint damage and pain sensitisation.
Grapiprant is a new option available for dogs who cannot tolerate or take NSAIDs.
B) Grapiprant is one of the newer medications available for arthritis. Grapiprant also targets arthritic pain by reducing the effect of PGE2. Whereas NSAIDs reduce PGE2 production by inhibiting general prostaglandin production, Grapiprant blocks PGE2 from binding to the EP4 receptor.
- Prostaglandin E2 (PGE2) is one of the main inflammatory proteins in arthritis. It contributes to the transition from acute to chronic maladaptive pain. PGE2 is produced by damaged tissues. When the PGE2 protein binds to the EP4 receptor in the joint, a pain signal is sent up the nerve to the brain. In chronic inflammation, PGE2 is continually being produced and the constant stimulation of the EP4 receptor causes both an increase in the number of receptors plus an increase in sensitivity of the receptors. This leads to constant and worsening pain signals to the brain – pain sensitisation. NSAIDs reduce pain and inflammation by inhibiting the cyclooxygenase (COX) proteins necessary for prostaglandin production, thus blocking the production of PGE2, and stopping the amplification cycle.
Grapiprant is a new option available for dogs who cannot tolerate or take NSAIDs.
B) Grapiprant is one of the newer medications available for arthritis. Grapiprant also targets arthritic pain by reducing the effect of PGE2. Whereas NSAIDs reduce PGE2 production by inhibiting general prostaglandin production, Grapiprant blocks PGE2 from binding to the EP4 receptor.
By reducing the production of all types of prostaglandins, NSAIDs can potentially cause stomach ulcers and affect kidney function, although this occurs uncommonly. Grapiprant can avoid these potential side effects. The downside of grapiprant is that because it is not reducing prostaglandin production, the PGE2 can still exert its damaging inflammatory effects as well as cause pain by other means.
Thus, Grapiprant only works for mild to moderate pain. Side effects still include mild transient inappetence, vomiting, and diarrhoea. Larger trials are still needed to determine its safety and effectiveness.
Anti-NGF monoclonal antibody is the newest revolutionary player to become available.
Anti-NGF monoclonal antibody is the newest revolutionary player to become available.
C) Anti- NGF monoclonal antibody, Bedinvetmab, is the newest treatment available for arthritis. In Australia, it is marketed as Beransa (Zoetis) and Librela (outside of Australia). Beransa is given as a monthly injection under the skin, providing pain relief and reducing inflammation within the joints. It is registered for use in dogs over one year of age.
Trials have shown remarkable improvements in a significant proportion of dogs. As this is a new product, long-term safety data is not available. However, the main side effect noted so far is mild, transient pain at the injection site.
Like PGE2, Nerve Growth Factor (NGF) is produced by damaged tissues in the joint. NGF binds to TrkA receptors on the end of nerves, triggering a pain signal that gets sent up the spinal cord to the brain. With prolonged stimulation, more TrkA receptors are produced, making the nerve endings more sensitive to pain signals and lowering the threshold for those nerves to be stimulated.
Like PGE2, Nerve Growth Factor (NGF) is produced by damaged tissues in the joint. NGF binds to TrkA receptors on the end of nerves, triggering a pain signal that gets sent up the spinal cord to the brain. With prolonged stimulation, more TrkA receptors are produced, making the nerve endings more sensitive to pain signals and lowering the threshold for those nerves to be stimulated.
Furthermore, binding of NGF to the TrkA receptors tells inflammatory cells to produce more NGF and other inflammatory proteins. Thus, NGF plays an important role in amplifying both inflammation (and therefore causing further joint damage) and pain. The anti-NGF antibody stops NGF from binding to the TrkA receptor, reducing inflammation and further damage, inhibiting the pain pathway, and treating and slowing the nerve sensitisation.
Because it is a new patented product, Bedinvetmab comes with a correspondingly higher price tag. However, it is a potential game-changer in the management of canine arthritis. What is not as clear yet is how the injections are to be integrated with other treatments, such as NSAIDs and the standard pentosan polysulphate “arthritis injections”. There are limited studies yet on administering Beransa and NSAIDs or the previous standard arthritis injections together.
6. Pentosan Polysulphate Sodium is the ingredient in the products we typically, up till now, have called “arthritis injections”.
Because it is a new patented product, Bedinvetmab comes with a correspondingly higher price tag. However, it is a potential game-changer in the management of canine arthritis. What is not as clear yet is how the injections are to be integrated with other treatments, such as NSAIDs and the standard pentosan polysulphate “arthritis injections”. There are limited studies yet on administering Beransa and NSAIDs or the previous standard arthritis injections together.
6. Pentosan Polysulphate Sodium is the ingredient in the products we typically, up till now, have called “arthritis injections”.
Arthritis involves significant destruction of the joint cartilage and a deterioration in the quality of joint fluid. Pentosan polysulphate is thought to stimulate the production of glycosaminoglycans, improving cartilage health and joint fluid production, thus improving joint lubrication.
It can also potentially inhibit proteins involved in cartilage destruction and has anti-inflammatory effects. The injections are given as a course of 4 weekly injections under the skin and many then go onto long-term monthly injections. Countless dogs have had these injections over the years. It has minimal to negligible side effects.
Many dogs with arthritis have shown remarkable improvement, whilst for others it has done nothing. Given such a positive track record in helping dogs with arthritis, I think the typical pentosan polysulphate injections are still here to stay.
Bella is a 12-year old Maltese Hunting Dog who has had recent difficult jumping and getting up and down. She sits with her back legs to one side to reduce pain in her right knee.
She is on a weight loss program, NSAIDs, omega-3 fatty acids (via sardines), and a course of Zydax (pentosan polysulphate sodium) injections. Her next step will be Beransa.
Secondary management options:
As arthritis progresses, the primary treatment options may not be enough to manage the pain and additional treatments may be incorporated.
1. Other oral pain management medications include gabapentin, paracetamol, opiates, amantadine, and cannabinoids.
A) Gabapentin and pregabalin are often used off-label when neuropathic pain is suspected. It is not fully understood how they reduce pain, but they dampen nerve signals and can also help reduce muscle spasms. They are not highly effective alone as a pain killer but are often given in conjunction with NSAIDs. The main side effect is drowsiness, but this lessens over time.
B) Acetaminophen (paracetamol) may be used off-label. It is not effective as a sole agent but may be added for additional pain relief.
Please Note: Never give to cats.
C) Opiates are potent pain killers that may be employed to control severe pain. However, most opiates come as injections or short-term pain relief patches, so are not practical for everyday use. Long-term use can also cause constipation. Opiates certainly can be used short-term for severe pain. Tramadol is modified opiate-like medication and practical as a tablet. Studies suggest it may not be a highly effective pain relief for dogs but may help as an additional medication when arthritic pain is severe.
D) Amantadine is not effective as a sole pain relief. With chronic pain, as the nervous system becomes more and more sensitised, the pain can become refractory to painkillers that were previously effective. Amantadine has a role in desensitising the nerves and may be used in conjunction with other painkillers for several weeks to restore their effectiveness.
E) Cannabinoids, such as cannabidiol (CBD) oil are also new entries to the management of arthritis. They have gained attention in recent years in the management of chronic pain in humans.
C) Opiates are potent pain killers that may be employed to control severe pain. However, most opiates come as injections or short-term pain relief patches, so are not practical for everyday use. Long-term use can also cause constipation. Opiates certainly can be used short-term for severe pain. Tramadol is modified opiate-like medication and practical as a tablet. Studies suggest it may not be a highly effective pain relief for dogs but may help as an additional medication when arthritic pain is severe.
D) Amantadine is not effective as a sole pain relief. With chronic pain, as the nervous system becomes more and more sensitised, the pain can become refractory to painkillers that were previously effective. Amantadine has a role in desensitising the nerves and may be used in conjunction with other painkillers for several weeks to restore their effectiveness.
Their mechanism of action is complex and not fully understood. There have been limited studies with mixed results on the effectiveness of CBD oil in managing arthritic pain in dogs. There is also limited safety information. CBD oil needs to be compounded and should only be acquired via a veterinary prescription from reputable compounding chemists.
2. Acupuncture has been shown in some studies to help with nerve and muscle pain, including arthritis. Results are usually subtle but positive.
3. Epitalis is a protein extracted from the cactus plant. It is marketed as 4Cyte.
2. Acupuncture has been shown in some studies to help with nerve and muscle pain, including arthritis. Results are usually subtle but positive.
Limited studies have shown it can reduce pain and increase mobility over a 6-week period, in some cases with a level of benefit comparable to giving NSAIDs.
4. Steroid injections into the joint are sometimes used for painful joints that are not responding to other treatment, mainly for palliative care.
Whilst they can provide short-term relief of pain, steroids can destroy cartilage and contribute to joint damage, so routine steroid injections are not recommended except for end-stage disease.
Experimental options:
5. Platelet Rich Plasma (PRP), Stem Cell, and Hyaluronic joint injections are still in their infancy. The most research has looked at PRP injections. PRP involves taking blood from an affected dog, processing the sample to produce a sample high in platelets, and injecting this into the joint of the same dog. Platelets release growth factors that stimulate blood vessel and cartilage formation and reduce cartilage death. Some studies have proven promising.
6. Laser treatment, Pulsed-electromagnetic Field therapy, Extracorporeal Shock Wave Therapy may be of benefit at reducing inflammation and promoting regeneration but studies are still limited.
A note regarding nutritional joint supplements:
A lot of nutritional supplements claim to help restore cartilage and reduce inflammation. However, many do not have sufficient evidence yet to back their claims.
In fact, there are now enough studies in both the human and canine field to show that Glucosamine and Chondroitin supplements do nothing in the management of arthritis. Substances being investigated that may have some future potential include avocado and soybean unsaponifiables (ASU), egg-shell membrane, and Beswellia Serrata (true frankincense).
Conclusion:
Arthritis is a progressive degenerative inflammatory disease. Left untreated, inflammation and pain can amplify to create an ongoing cycle of progressive destruction and chronic, worsening, refractory pain. Successful management requires identifying arthritis early and employing multiple strategies to reduce and stop inflammation and pain before it intensifies and causes further damage or pain. Early identification and intervention of arthritis is critical to achieve a maximal quality of life.
Conclusion:
Arthritis is a progressive degenerative inflammatory disease. Left untreated, inflammation and pain can amplify to create an ongoing cycle of progressive destruction and chronic, worsening, refractory pain. Successful management requires identifying arthritis early and employing multiple strategies to reduce and stop inflammation and pain before it intensifies and causes further damage or pain. Early identification and intervention of arthritis is critical to achieve a maximal quality of life.
About Dr. Meredith Crowhurst
Dr Meredith Crowhurst is a Melbourne-based locum veterinarian. A Melbourne University graduate with more than a decade of experience, she has extensive consultation and surgical experience and has worked with dogs, cats, rabbits, guinea pigs, rats, mice, birds, and various other animals.
Meredith understands the importance of the human-animal bond. Her aim is to treat pets and their owners with empathy and compassion, delivering the best standard of care.
Previously, Meredith completed a Bachelor of Arts/Bachelor of Science degree and completed her PhD in the biomedical sciences. As well as treating animals, Meredith’s aim is to educate and make medical science knowledge accessible for all.
You can contact her at Tarneit Mobile Vet and soon also at www.centralvet.com.au. Follow her on Instagram at instagram.com/
Meredith understands the importance of the human-animal bond. Her aim is to treat pets and their owners with empathy and compassion, delivering the best standard of care.
Previously, Meredith completed a Bachelor of Arts/Bachelor of Science degree and completed her PhD in the biomedical sciences. As well as treating animals, Meredith’s aim is to educate and make medical science knowledge accessible for all.
You can contact her at Tarneit Mobile Vet and soon also at www.centralvet.com.au. Follow her on Instagram at instagram.com/
References:
Barbeau-Grégoire M, Otis C, Cournoyer A, Moreau M, Lussier B, Troncy E. A Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis. Int J Mol Sci. 2022. 23(18):10384.
Mosley C, Edwards T, Romano L, Truchetti G, Dunbar L, Schiller T, Gibson T, Bruce C, Troncy E. Proposed Canadian Consensus Guidelines on Osteoarthritis Treatment Based on OA-COAST Stages 1-4. Front Vet Sci. 2022. 9:830098.
Pye C, Bruniges N, Peffers M, Comerford E. Advances in the pharmaceutical treatment options for canine osteoarthritis, JSAP. 2022. 63(10): 721-738.
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