Effectively diagnosing, treating equine degenerative joint disease - DVM
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Effectively diagnosing, treating equine degenerative joint disease

DVM Best Practices

Figure 1: Factors involved in the enzymatic degradation of articular cartilage matrix in equine OA. IL-1= interleukin 1; TNF-alpha= tumor necrosis factor alpha; FGF= fibroblast growth factor; PGE= prostaglandin; PLA-2= phospholipase A2; uPA= urikinease plasminogen activated; tPA= tissue plasminogen activator; PA= plasminogen activator; PGE2= prostaglandin E2; TIMP= tissue inhibitor of metalloproteinases.
Treatment options There are a number of treatment options in treating OA or DJD. Non-steroidal anti-inflammatory drugs (NSAIDs) have been commonly used. Phenylbutazone would be the most frequently administered. Prolonged use or high dosages have side effects, particularly to the GI tract and kidneys. In humans there is increased use of specific COX-2 inhibitors. Recent experience by the author with carprofen (Rimadyl®) in the horse is exciting (used in patients exhibiting signs of GI disturbance or nephrotoxcitiy have done well on Rimadyl using the product licensed for the dog).

The use of intra-articular hyaluronin or hyaluronic acid (HA) has been made for synovitis or OA in the horse since 1975. More recently two products have been licensed for use in human OA. Clinical experience in the horse is that HA is very useful for mild to moderate levels of synovitis, but has limitations with severe synovitis or when there is significant osteoarthritis present. However, used in combination with corticosteroids, considerable benefit can be obtained and there is clinical evidence that HA can placate the side effects of certain corticosteroids. In the past 10 years, use of intravenous HA has become common. There is only one licensed product made by Bayer (Legend® in the United States, Hyonate® elsewhere). In our experimental OA mode, use of 40 mg of Legend IV has been shown to be very effective in providing prolonged anti-inflammatory activity. It has also been used considerably on a "prophylactic" basis in the athlete. While there is anecdotal evidence of value, it has not been able to be demonstrated in controlled studies yet.

Intra-articular corticosteroids are still a major part of the armamentarium of equine clinicians working with the equine athlete. Benefits versus deleterious effects have become clarified in the past 10 years with controlled studies in an experimental OA model at CSU. Betamethasone esters (Betavet®, Schering) when the study was done, was shown to have no side effects on the articular cartilage, while promoting significant anti-inflammatory activity. Unfortunately, that product has become unavailable, as has the human product Celestone®. Clinicians have had to resort to compounding and good product is available through these channels. Triamcinolone acetonide (Vetalog®) not only has no negative side effects when evaluated in the model of OA, but joints treated with triamcinolone acetonide had articular cartilage in better condition than in the control placebo groups. Clinicians are concerned about the potential for laminitis with the use of this product, but it has been used very frequently without side effects as long as the total body dosage remains relatively low. On the other hand, work in the CSU model with methylprednisolone acetate (Depo-medrol®) has confirmed other work demonstrating that this medication will contribute to pathologic deterioration in the articular cartilage. Its use has become less frequent, but it is still used commonly because of its length of action as well as the relative lack of availability of other licensed products. It is important to try and minimize repeated use of this medication in joints other than the distal tarsal joints.

The only licensed glycosaminoglycan product is Adequan®. The subject of relative values of glycosaminoglycan products (including the oral ones) is addressed in the article on p. 8. The author has always considered PSGAG as the gold standard of a chondroprotective drug in the horse. It has been shown to inhibit the osteoarthritic process. It is commonly used after surgery when there is significant cartilage loss, exposure of subchondral bone and minimizes the progression of the osteoarthritic process in these cases. A recent development is the testing of pentosan polysulfate, which should be available relatively soon and will offer another systemic option.

Suggested Reading.
Oral nutraceuticals is an area of great controversy. There is certainly good in vitro evidence in the horse for the beneficial effects of glucosamine and chondrosulfate in inhibiting the osteoarthritic process. There have also been other experiments showing absorption of these products, but none demonstrated efficacy in inhibiting the osteoarthritic process in vivo in the horse. A recent meta-analysis of the use of these products in humans for the treatment of knee osteoarthritis provides food for thought. According to a recent article in the Journal of the American Medical Association on meta-analysis, studies in the knee generally are of low to mediocre quality, are sponsored largely by manufacturers and show strong evidence of publication bias. It was found that positive responders in the treatment groups were enthusiastic about glucosamine about a treatment and had negative attitudes towards conventional medical treatments for knee OA. Responders in both groups had modest criteria for treatment efficacy. They expected modest relief of pain and only moderate improvement in ability. Responders were more likely to have had positive experience with compliment therapies in the past.

The recent trend has been for the development of specific biologic therapies. The use of metalloproteinases inhibitors was the initial biological therapy evaluated, but results have been disappointing. Specific therapy aimed at inhibiting cytokines shows promise. TNF alpha is a cytokine important in rheumatoid arthritis in humans and there are licensed inhibitors now available. TNF alpha does not seem so important in equine OA, but IL-1 is and work in our laboratory showed excellent results providing the gene for IL-1 receptor antagonist using a viral vector. The gene therapy protocol showed significant inhibition of the osteoarthritic process in the horse.


Source: DVM Best Practices,
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