Degenerative joint disease is a common malady of the horse. It most frequently strikes the hocks, front fetlocks, and front navicular bones, and its consequences can be severe. In fact, degeneration of the joints is the most common reason for retirement of a horse from athletic use. What mechanisms underlie this joint erosion, and what can be done to stop it?

In the limbs of a healthy horse, bone meets bone within the specialized confines of a fluid-filled structure termed the synovial joint. The synovial joint is designed to allow free movement between the ends of the bones, which are encased by a sack-like joint capsule. The capsule's outer layer is tough and fibrous, and along with additional ligaments, it connects the bones and restricts their relative movement to the desired directions. Inside the joint capsule, the bones are coated with thin layers of smooth cartilage, while the capsule itself is coated with a delicate connective tissue termed the synovial membrane. This membrane is responsible for producing the lubricant component of the synovial fluid that fills the joint cavity. With a cushion of lubricant interposed, the opposing surfaces of cartilage can slide easily against one another.

With disease, however, the structure of the joint is affected such that this smooth, low-friction movement is no longer possible. The term degenerative joint disease, or DJD, refers to a group of disorders resulting in a common outcome: progressive deterioration of the health of the joint cartilage, along with destructive changes to the associated bone and soft tissues. The surface of the joint cartilage becomes split and fragmented, and the synovial lining of the joint capsule may become inflamed, causing the joint to swell with abnormal, excessive fluid. The affected horse shows pain, lameness, and loss of normal joint function.

The health of the joint cartilage depends on a delicate and complex balance between the formation and the degradation of its components. Because cartilage does not receive its vital nutrients directly from blood vessels, supplies are limited and may be inadequate in times of increased cartilage cell turnover. Virtually any insult to the cartilage may affect its nutritional state and result in tissue damage, including such common events as traumatic injury to the joint, mechanical misalignment, vascular disease, use of some non-steroidal anti-inflammatory drugs, and either total immobilization or excessive activity.

Current strategies in prevention and management of DJD are focusing not only on the control of mechanical trauma, but also on medical interventions that can affect the nutritional health of cartilage. The cascade of biologic enzymes and mediators that regulate cartilage metabolism is complex; in general, therapy aims to remove the substances promoting the degradation of cartilage and to enhance those agents preventing it. Whether medical therapy is used alone or as an adjunct to a surgical procedure, the desired outcome is to restore and maintain normal joint function by alleviating joint pain, decreasing joint inflammation, and protecting the cartilage from further injury.

Non-Steroidal Anti-Inflammatory Drugs

Non-steroidal anti-inflammatory drugs, commonly referred to as NSAIDs, are a family of compounds useful in reducing inflammation, pain, and fever. This is the most commonly used family of medications for lameness-associated problems, whether they be joint or soft tissue. The most widely used NSAID in equine medicine is phenylbutazone, or Bute. NSAIDs also are used in horses for control of inflammation and pain after surgery for joint disease. Discriminant use at low doses can keep a horse in training and comfortable because NSAIDs decrease effusion in joints and decrease low-grade lameness. These drugs are not a panacea, however. Systemic side effects have been reported in horses and ponies with use of NSAIDs, especially when the dose is high or when administration is prolonged. Furthermore, the long-term catabolic effects of these drugs on cartilage cell metabolism are not known.

Corticosteroids

Corticosteroids are potent reducers of inflammation, pain, and fever. Though both the short-acting and long-acting varieties are frequently used to treat inflammation in horses, the practice of injecting these drugs directly into the joint is controversial. By decreasing inflammation within the joint, corticosteroids may enable the return of normal synovial fluid properties and hyaluronic acid content, improving cartilage nutrition. Corticosteroids are capable of both suppressing the synthesis of some destructive biologic agents and increasing the synthesis of some inhibitors of these agents. However, studies have also shown that corticosteroids have the potential to decrease the metabolic activity of cartilage, making it prone to injury. The full range of their effects on cartilage-cell metabolism has not been clarified. Ideally, a dose of corticosteroids should be determined that provides relief from inflammation and pain but does not interfere with cartilage cell metabolism. If this is not possible, combination drug therapy should be considered.

Superoxide Dismutase

Orgotein is a naturally occurring enzyme preparation that is licensed for intramuscular use to treat inflammatory joint conditions in the horse. Though it presumably has anti-inflammatory activity, results of clinical trials regarding its efficacy have been inconclusive. Some field trials show a positive effect on symptoms of DJD, but this same effect has not been reproduced in the laboratory. Studies of the effect of orgotein on inflammation when injected directly into the joint have also yielded conflicting results. Until more experimental evidence is presented to justify its effectiveness, clinical use of orgotein is probably not indicated. Because no proof currently exists that these drugs can be absorbed orally, oral forms of superoxide dismutase are also not recommended.

Chondroprotective Agents

Chondroprotective agents are a class of compounds that perform any of a variety of functions ultimately resulting in improved cartilage health. They may support or enhance the production capabilities of the cartilage cells, support or enhance the production of hyaluronic acid, inhibit destructive enzymes or mediators of inflammation, or remove or prevent abnormal deposits in the joint capsule fluid or blood vessels. These beneficial compounds are themselves naturally occurring building blocks or components of cartilage and synovial fluid. Following the theory that joint health may be improved by administration of additional chondroprotective agents, researchers have found ways either to extract and purify these components or to synthesize similar compounds in the laboratory.

Some of the agents that have been tested for their ability to combat DJD are hyaluronic acid, polysulfated glycosaminoglycans (Adequan), glucosamine salts, chondroitin sulfates (including the synthetic form known by the trade name Arteparon), pentosin polysulfate, and purified naturally occurring proteoglycan marketed under the name Rumalon. Arteparon and Rumalon are traditionally administered by injection, but the glucosamine salts and the chondroitin sulfates may also be given orally.

Hyaluronic acid, a normal component of the synovial fluid and joint cartilage, is a soft-tissue boundary lubricant which also functions to filter certain compounds from the synovial fluid and to reduce inflammation. Studies have shown that when inflammation is present in a joint, both the concentration and average molecular weight of hyaluronic acid are decreased, hampering its function. In many clinical trials, administration of extra hyaluronic acid to lame horses either intravenously or directly into the affected joints resulted in clinical improvement, but its mechanism of action is still not completely understood. Research indicates that the high-molecular weight preparations are the most cost effective, and that maximum results are achieved if the drug is administered after the initial acute inflammation has subsided. When used properly, a single injection of hyaluronic acid into an affected joint (without serious cartilage damage) may enable a horse to return to work after only two or three days of rest.

Polysulfated glycosaminoglycans, or PSGAG, are commonly known by the trade name Adequan. This semisynthetic compound, which must be injected, acts on the synovial membrane to enhance the natural production of hyaluronic acid. PSGAG also inhibit the effects of several of the biologic enzymes that tend to degrade joint cartilage. Research suggests that PSGAG may be more effective for prevention than for therapy; therefore, the earlier in the process of DJD that the drug is administered, the more beneficial will be the effects. PSGAG are generally injected into the muscle, but may also be injected directly into the joint. Because injection into the joint can cause infection, strict aseptic technique and concurrent antibiotic administration are indicated.

Oral chondroprotectants include glucosamines, which are particularly effective chondroprotective agents because they serve both as a raw material and as a regulatory stimulus for cartilage component synthesis. Studies of DJD in Europe concluded that orally administered glucosamine salts cause significant reduction in clinical joint pain, tenderness, and swelling.

Chondroitin sulfates, which provide beneficial clinical effects similar to those of the glucosamine salts, are both major components of cartilage and inhibitors of cartilage-destructive enzymes. Long-term clinical trials of oral and injectable chondroitin sulfates revealed a slowing of the course of DJD, improvement in joint function, a decrease in joint pain and the need for pain relief, and a renewed capacity for work. The actions of glucosamine salts and chondroitin sulfates are synergistic, and combinations of these therapies have great potential to improve the supply of nutrients to cartilage and thus prevent impairment.

An important factor in selecting a chondroprotective agent from the marketplace is assurance of purity. Though most products claim to be pure, methods of assessing purity differ. Particularly in the case of chondroitin sulfates, purity as determined by titration or neutralization may appear much higher than if assessed by the more accurate specific assay methods. Clearly, if a product's composition is not equivalent to that used in the research, it is unlikely to perform to the same standard.

Cosequin is the trade name for a specific patented combination of glucosamine, chondroitin sulfate, and manganese ascorbate. These chondroprotective agents act synergistically to stimulate the formation of synovial fluid and to enhance the repair and regeneration of cartilage. Cosequin, which is administered orally in powder form, can be used at a maintenance level to aid in prevention of cartilage degeneration. If cartilage damage has already occurred, a high loading dose is required, which then can be adjusted based on clinical response. The time for response is dose-related and depends on the severity of the condition.

Other Medical Therapies

Dimethylglycine is a nutritional supplement. Some human athlete trainers claim that it enhances stamina by improving circulation, reducing lactic acid build-up, and preventing muscle fatigue. Though it does not offer any joint protective properties, it is currently quite popular on training grounds. The efficacy of this supplement has not yet been tested in controlled studies.

Methylsulfonylmethane, a metabolite of dimethylsulfoxide (DMSO), has been used by some trainers of equine athletes in an attempt to reduce joint injuries. Though sulfur from methylsulfonylmethane is involved in the production of proteins and is part of the complicated cascade of metabolic reactions resulting in cell energy production, its usefulness is merely presumed. No controlled studies have yet been performed to evaluate its efficacy.

Any horse that is lame as a result of joint disease should be rested. Though cessation of work is often undesirable, the long-term benefits to the horse's health will outweigh the short-term drawbacks of interruption of a work or training schedule. Studies have shown that horses with good cardiovascular health can sustain their condition without training for five weeks.

Rest is important with acute cases of inflamed joints even if radiographs show no evidence of DJD in the underlying bone. Injury to cartilage is not visible on radiographs, and the point at which the damage becomes irreversible is not known. Joint healing, particularly after surgery, may be aided by continuous passive motion of the joint (without weight or strain). This can be accomplished by swimming or passive range-of-motion exercises. Such exercises help restore flexibility and promote blood and lymph flow. Physical therapy in horses, however, is limited by available facilities and personnel. Most clinicians must depend on pain to guide the horse as to how much weight can be safely borne on an injured joint. For this reason, use of pain-relieving drugs must be judicious.

Joint lavage, in addition to removing fragments of bone and cartilage, can also be used to flush the joint of destructive enzymes and mediators of inflammation. PH-balanced solutions are recommended.

Medical therapy is only one aspect of a total management program for equine soundness. Rest and physiotherapy are important components of a complete therapeutic plan, while some conditions, such as chip fractures, also require surgical intervention. Yet the prospects for more effective medical therapy of equine lameness continue to improve, especially in regard to the newer nutritional alternatives. Further development of the principles of chondroprotection will doubtless interrelate the provision of chondroprotective nutritional agents with the diagnosis and correction of abnormal joint load forces, the judicious use of selected pain relievers, and general improvement in horse health and exercise habits.

About the Author

R. Reid Hanson, DVM, Dipl. ACVS

R. Reid Hanson, DVM, Dipl. ACVS, joined the surgical faculty at Auburn University in 1992, and is currently a Professor of Equine Surgery and Lameness. He is the author of over 180 scientific articles, abstracts, presentations, and book chapters related to equine surgery, lameness and critical care. Dr. Hanson is also an award-winning speaker, speaking to international audiences about these important topics. In his free time he enjoys competitive swimming and training. More information on Dr. Hanson can be found at www.vetmed.auburn.edu/faculty.dcs-faculty/hanson.

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