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The Medical Management of Osteoarthritis

The management of Osteoarthritis (also known as OA, Degenerative Joint Disease) continues to be a very common therapeutic dilemma for the small animal veterinary practitioner. It has been estimated that approximately 8 million canines (or roughly 20% of the adult canine population) and 20% of cats over 12 years of age in the United States suffer from osteoarthritis.

Currently, there is still no "cure" for OA. With this in mind, the goals of treatment of OA remain relief of pain, improvement in joint function, and a slowing or cessation of progression. While surgery is often utilized in the initial treatment of patients with certain types of OA, medical management remains as a very important aspect of the long-term therapy for many patients. When considering medical alternatives for the treatment of OA, several factors must be taken into account. Product safety, locally as well as systemically, is a prerequisite for use. The ease, method and frequency of administration, along with cost are also important aspects relating to client acceptability and compliance.

Finally, efficacy plays an obvious, yet poorly defined role in a product's use. Following is a brief synopsis of the more commonly used medical therapies for OA in the companion animal. These products include non-steroidal anti-inflammatories (NSAIDS), oral disease modifying osteoarthritis agents, polysulfated glycosaminoglycan, hyaluronic acid, and pentosan polysulfate. Attention will be paid to the pharmacology of each product, as well as evidence for efficacy and safety. For a more detailed review, the reader is referred to July 1997 edition of Veterinary Clinics of North America- Spencer Johnston, Guest editor.

As with many conditions in veterinary medicine, a thorough consultation with the client specifically discussing patient management objectives must be initiated prior to prescribing any medical therapy. Among these include particular attention to weight control and exercise modulation. Also, an in-depth orthopedic examination must be performed to exclude surgical conditions that either caused or exacerbated the arthritic condition. For example, an un-repaired torn cranial cruciate ligament will lead to a marked progression of arthritis in the stifle, regardless of medical therapy, unless the stifle is first debrided and stabilized via surgery. Medical management should never be viewed as a replacement to appropriate surgical therapy; rather it should be viewed as an adjunctive therapy that adds to the veterinarian's armamentarium.

Perhaps the best-recognized and most widely used group of medications in the management of OA is the non-steroidal anti-inflammatories (NSAIDS). Included in this group are: aspirin, etodolac, ibuprofen, ketoprofen, carprofen, phenylbutazone, naproxen, piroxicam, and acetaminophen. This group of agents acts primarily by reducing the amount of inflammatory prostaglandins, particularly prostaglandin PGE2 through inhibition of the cyclo-oxygenase enzymes. This results in decreased vasodilatation, edema and vascular permeability as well as an increased pain threshold. Other beneficial effects such as inhibition of oxygen free radical production, stabilization of lysozomal membranes and decreased neutrophil activity may also occur. With these positive effects, however, there are some potentially substantial side effects. The most common side effect of NSAID usage is gastrointestinal toxicity, resulting in ulceration and, possibly, perforation. Renal disease may also be exacerbated, via the inhibition of the natural prostaglandins needed for kidney perfusion. Additionally, several studies have shown a decrease in proteoglycan synthesis in animals receiving aspirin. It is also important to note that, of the commonly used products, only phenylbutazone, meclofenamic acid, carprofen, and etodolac are approved for use in the canine by the U.S. Food and Drug Administration. This group of medications is often very effective in the short and long-term management of osteoarthritis, however, given the potential deleterious effects with chronic administration, alternate therapies have been evaluated.

A relatively new concept for OA therapy involves products that are administered orally and contain components found in normal hyaline cartilage. These products are known as oral, disease modifying osteoarthritis agents (ODMOA). These products are reported to have a positive effect on cartilage synthesis, as well as an inhibitory effect on the degradative enzymes seen in OA. Most of these oral agents contain precursors of normal hyaline cartilage, predominantly glucosamine and chondroitin sulfates. As mentioned, these products are not only used in the synthesis of normal hyaline cartilage, but they have also been shown to exert enzymatic effects, which are beneficial to cartilage. The exact mechanism of action remains unclear, but several hypotheses have been discussed. One possible method of action revolves around the disparity between cartilage synthesis and breakdown in OA. It has been suggested that the reason for cartilage damage stems from a relative lack of "building blocks" for normal cartilage in the face of increased destruction. In this theory, the supply of precursors for normal cartilage is the rate-limiting step in repair, resulting in more destruction than construction. The oral agents are proposed to provide the "building blocks" in supra-physiologic quantities, shifting the equation back to an anabolic, or productive phase. Perhaps a more plausible suggestion centers solely on the chemical reactions seen with these products. Glucosamine has been shown to have cyclo-oxygenase independent, anti-inflammatory properties, as well as scavenge oxygen-derived free radicals and stimulate hyaluronic acid synthesis. Chondroitin sulfate has been demonstrated to stimulate glycosaminoglycan and collagen synthesis, inhibit degradative enzymes such as metalloproteinases, and reduce certain types of inflammation. My clinical experience with this product has been very favorable for a variety of conditions. Positive aspects of the product include, twice daily oral administration and few reported side effects, while a negative in many cases is the product's cost. It is important to note that there are many products available, however, studies have shown a wide variety of bioavailability from product to product and that only one product (Cosequin) currently has scientific evidence to support its safety and efficacy.

Although Hyaluronic acid is widely used in the equine for management of OA, there is little scientific literature regarding its use in the companion animals. HA is a glycosaminoglycan found in normal joints. It is a major component of articular cartilage, as well as the lubricating joint fluid. HA is usually administered intra-articularly and is thought to act by increasing the viscosity of the arthritic joint. This allows for better nutrition and protection for the articular chondrocytes. HA may also have direct anti-inflammatory effects, free radical scavenging properties and chemotactic inhibition of inflammatory cells and their enzymes. I have no clinical experience with this product.

Polysulfated glycosaminoglycans are commonly used in the management of OA. Of these, Adequan is the most widely recognized form of this type of product. This product has been shown to increase cartilage synthesis, while at the same time, decreasing cartilage degradation by destructive enzymes such as metalloproteinases. My clinical experience with this product has been very favorable, with approximately 75% of patients responding. However, the client should be informed of some potential complications: the need for repeated subcutaneous or intramuscular injections, the cost, and the potential exacerbation of any clinical or sub-clinical bleeding disorders.

Pentosan polysulfate is an anti-OA product that is derived from a plant. It is thought to have a similar mechanism of action to that of PSGAGS. Unfortunately, these products are currently not approved for use in the United States, however they show promise as a new therapy for the treatment of OA.

Chronic use or high doses of corticosteriods have been demonstrated to be detrimental to hyaline cartilage, so most orthopedic surgeons do not recommend the use of corticosteriods for the management of osteoarthritis in the companion animal. Other side effects include increased thirst and urination, and iatrogenic hyperadrenocorticism (Cushing's disease). Because there are a wide variety of more appropriate therapies available, I do not recommend the use of steroids in the management of osteoarthritis.

The best method of incorporating these advances is to address each individual patient, paying particular attention to those factors that may positively or negatively impact on the success of the therapy. Often this results in the combination use of several different therapies, representing many of the different modalities available to the veterinarian. Whatever the specific protocol, the end result is frequently a happier, healthier pet. Over the last several years dramatic progress has been made in the medical management of canine and feline degenerative joint disease, resulting in numerous options available to the veterinarian and the client. In the vast majority of cases, osteoarthritis is no longer a death sentence for our companion animals.

The Medical Management of Osteoarthritis
by Paul S. McNamara, DVM, Diplomate American College of Veterinary Surgeons
Reprinted with Permission ~ 22 May 2000

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