Diagnosis: Equine Joint Disease
When your horse’s joints start to wear, what therapeutic options can you use to keep him comfortable and functional?
Osteoarthritis, or degenerative joint disease, is the No. 1 cause of poor performance in athletic horses. Heavy bodies with relatively minimal joint surface area, limited soft tissue support of the lower extremities, and jobs that require complicated movements predispose horses to developing osteoarthritis (OA).
A joint is made up of many components, each of which can suffer a primary injury that initiates a cascade of inflammatory events. This “domino effect” eventually leads to joint remodeling. In biological systems, explains Mark Revenaugh, DVM, owner of Northwest Equine Performance, in Mulino, Oregon, self-repair mechanisms can overcompensate when trying to manage the degradation and repair process.
“The bone reaction that occurs around the joint in osteoarthritis is the manifestation of the joint’s attempt to stabilize, similar to muscle spasms in the region of a back injury,” he says. While the body’s attempt might be in good interest, its cause is best stopped early and effectively. Breaking the inflammatory cycle and helping promote a healthy joint environment in the face of work-related stress is crucial to managing your horse’s comfort, performance, and longevity. Early and directed therapy to minimize inflammation will help reduce progressive changes. For this reason it is important to understand the treatment protocols aimed at maintaining damaged cartilage and preventing further degradation.
Depending on the condition or injury, your veterinarian might take a number of approaches to treating the joint, from exercise and weight control to systemic and intra-articular medications. While traditional therapies can help many arthritic conditions, recent advances in regenerative, or biologic, pharmaceuticals have not only provided more treatment options but also altered the way veterinarians approach problems.
“There are two main strategies for management of osteoarthritis,” says Revenaugh. “One is to shut down the inflammatory process to decrease pain (symptom-modifying), and the other is to create a healing environment (disease-modifying).” Symptom-modifying therapies reduce clinical signs and provide relief from discomfort, while disease-modifying therapies aim to inhibit disease progression. Ideally, the goal is to both reduce clinical signs and inhibit the disease process. Let’s review how the available therapies work.
Non-steroidal anti-inflammatory drugs (NSAIDs) are mainstays of pain management in horses with OA. The NSAIDs veterinarians most commonly administer include phenylbutazone (Bute), flunixin meglumine (Banamine), firocoxib (Equioxx), and ketoprofen (Ketofen). All have similar mechanisms of action that revolve around inhibiting an enzyme called cyclooxygenase (COX), which produces inflammatory mediators. They do this by impairing COX production, which reduces inflammation and pain. Each NSAID has its own unique properties that might make it better suited to specific conditions. Clinically, phenylbutazone seems to be more potent than other options, and veterinarians often administer it when dealing with acute or moderate to severe pain. They often administer flunixin to control abdominal pain and fever; however, it helps reduce musculoskeletal inflammation, as well. Firocoxib blocks a pathway of COX and has less deleterious effects on the gastrointestinal and kidney systems than other COX inhibitors but is considered less potent than other NSAIDs. Thus, veterinarians often prescribe firocoxib for chronic long-term maintenance.
These pillars of pain control can successfully alleviate discomfort caused by arthritis, and they’re one of the most reached-for therapies because they’re easy to use.
Systemic “chondroprotective” (joint-protecting) injectables have shown some promise in reducing clinical signs of OA and modifying the disease process. The most commonly used therapeutic and prophylactic (preventive) treatments include injectable polysulfated glycosaminoglycan (PSGAG, Adequan) and hyaluronic acid (HA, Legend). Both are synthetic analogs of constituents found in normal joints. Polysulfated glycosaminoglycans are structural components of cartilage, and HA is a significant component of synovial fluid and to some extent cartilage.
Adequan was originally intended for intra-articular (IA) administration. However, early study results revealed a higher incidence of joint sepsis (infection) after IA injection than with other joint treatments. Intramuscular administration then grew in popularity. Veterinarians still don’t completely understand PSGAG’s exact mechanism of action, but evidence suggests it has an anti-inflammatory effect, helps stabilize the cartilage matrix, and inhibits degradative enzymes that contribute to OA. While limited scientific data support the efficacy of IM administered PSGAG, many anecdotal reports show favorable results.
Hyaluronic acid lubricates, adds viscosity (thickness) to joint fluid, and inhibits inflammation within the joint. Veterinarians commonly administer IV HA, often preventively; however, no evidence supports its ability to prevent joint disease. One study out of Colorado State University does support its use in treating OA. In it, IV Legend improved clinical lameness and synovial membrane health and reduced inflammatory mediators.
Regenerative and biologic medicine is evolving rapidly, providing steroid-free joint treatment options. These therapies can serve as substitutes for conventional treatment with corticosteroids, making them particularly useful for managing joint disease in horses with metabolic issues or periarticular soft tissue injuries.
“The severity of the issue within the joint can be a driving factor in the choice of a biologic over a corticosteroid,” says Carter Judy, DVM, Dipl. ACVS, staff surgeon at Alamo Pintado Equine Medical Center, in Los Olivos, California. “In cases with large articular defects, or cartilage compromise, a biologic is likely a better choice than a steroid.”
Most current biologic therapies involve collecting and concentrating the horse’s natural anti-inflammatory and regenerative proteins or cells so they can be injected into an area of pathology (disease or damage) in the same horse. The most commonly used biologic treatments for osteoarthritis in the horse are autologous conditioned serum (ACS), autologous protein solution (APS), platelet-rich plasma (PRP), and mesenchymal stem cells (MSCs). (To review how these therapies work, see TheHorse.com/189071.)
Revenaugh believes reasonable proof exists that some biologic therapies can be used to treat joint disease effectively, but he notes that further research and development are needed because many reports of success remain anecdotal.
“As far as biologics go, there are certainly anti-inflammatory properties, but they aren’t very well-understood at this time,” he says. “With that said, in my opinion biologics work better than steroids in many cases. The downsides are that they are a lot more expensive, need more equipment to produce, and typically have delayed onset of effect.”
Understanding the benefits and drawbacks of each biologic modality can be difficult, so it can be challenging to select one. Judy’s decision is “often driven by a combination of cost and availability of the biologic,” he says. “Some biologics, like cultured mesenchymal stem cells, take significant time to process, while others, like PRP, IRAP (trade name of ACS), and combination therapies can be more quickly obtained and utilized in the same visit. How a horse has responded previously is also an important consideration. If they have done well with one modality, then sticking with it is likely the best option.”
Polyacrylamide hydrogel is a synthetic resin similar to HA, but researchers have shown it has a longer-lasting viscous effect within the joint, because it is nondegradable. In intra-articular use it adheres to the synovial lining, which might reduce exposure to inflammatory molecules.
The gel integrates into the synovial lining and capsule over a short period. In some results researchers suggest it forms a cushionlike membrane with increased elasticity and strength. These actions are supposed to help reduce synovitis (inflammation of the synovial membrane) and its downstream deleterious effects.
Many veterinarians anecdotally feel this therapy is best used in end-stage OA joints as a last resort, possibly because of its somewhat permanent uptake in the synovial membrane and limited long-term studies. Peters has had success using polyacrylamide hydrogels on top-level competition horses and says “most have been end-stage, higher-motion joints, predominantly fetlocks. These have been worn-out joints with cartilage loss or joints that just don’t seem to respond for a long enough time to conventional or biologic treatment. It appears to work positively and allow horses to continue at current levels of activity for longer periods.”
Shock Wave Therapy
Not all OA treatments are medications. Take, for example, extracorporeal shock wave therapy (ESWT). Shock waves are acoustic sound waves with very high amplitudes and rapid rise times. In horses ESWT has shown promising results as a therapy for arthritic joints. The mechanism by which it works on OA remains unclear, but evidence suggests it might offer disease-modifying effects such as improved neovascularization (new blood vessel growth) and recruitment of mesenchymal stem cells. Veterinarians and researchers have also consistently noted analgesic (pain-relieving) effects.
The therapies listed are the most relevant, researched, and proven at this time. Novel treatments such as alpha-2-macroglobulin and virally mediated gene therapy show some promise, but we currently know too little about them to form adequate opinions. Alpha-2-macroglobulin is a protein found in blood that inhibits the action of catabolic proteases (tissue-damaging enzymes) involved in the osteoarthritis disease cascade. While we know little about its therapeutic function, some practitioners are using it and reporting favorable results.
Gene therapy is perhaps the most exciting potential therapy on the horizon. In short, it involves using viruses (that can’t replicate in horses) as vectors to implant genes coding for the production of anti-arthritic proteins into diseased joint tissue cells. These “infected” tissues continuously produce high levels of anti-inflammatory proteins in the synovial fluid and surrounding tissue. Colorado State University researchers have been studying this modality with promising results.
Osteoarthritis is a complex disease process that can appear in many ways. Currently, veterinarians have a number of treatment and management methods at their disposal. Depending on the specific case, however, some options might be better suited than others. Corticosteroids and NSAIDs are mainstays that veterinarians administer widely with positive response. Biologic and regenerative treatments seem to help, but we still have more homework to do, says Judy.
Polyacrylamide hydrogels and therapies that help increase joint fluid’s viscoelastic properties show potential and are on the rise. Novel methods such as gene therapy are in the earliest of research stages but might one day completely change the way we treat musculoskeletal injuries. With all the current therapy options, there’s not one panacea.
“Because each joint injury may have some ‘uniqueness’ to it, it follows that not one treatment will be the cure-all,” says Peters. “In addition to that, how horses are managed following a specific treatment has an important bearing on whether a treatment is a success.”
Regardless of the therapy you and your veterinarian ultimately choose for your horse, understanding its concepts and limitations will help you form appropriate expectations for its efficacy.
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