Nonsurgical management of osteoarthritis and pain (Proceedings)
Degenerative joint disease or osteoarthritis is typically a progressive disorder that affects diarthrodial joints.
Degenerative joint disease (DJD) or osteoarthritis (OA) is typically a progressive disorder that affects diarthrodial joints. It has been defined as "an inherently noninflammatory disorder of movable joints characterized by deterioration of articular cartilage and by the formation of new bone at the joint surfaces and margins". Osteoarthritis can develop from instability, chronic inflammation, incongruity or disease process that creates cellular pathology in the joint. In the dog, OA is usually associated with an inciting cause such as elbow or hip dysplasia. With these and other diseases that cause OA in the dog, OA begins with a disruption of the surface layer of the articular cartilage, and this physical damage initiates biochemical alterations that result in degradation of joint tissues. While arthritis is not an inflammatory based disease, the clinical symptoms associated with arthritis certainly can be associated with inflammation of the periarticular tissues. Prior to instituting treatment a definitive diagnosis must be made, beginning with the patient signalment. Osteoarthritis can affect dogs of any age but as age increases, intuitively the probability of OA developing and causing clinical signs increases. Owners might report that their dog tires easy when attempting to exercise, is reluctant to use stairs or jump, has a lameness or pain in the morning or after exercise, or has a change in behavior. The clinical signs may wax and wan over a period of days or weeks. On physical exam the diagnosis can be made by finding muscle atrophy, localizing pain to a joint(s), determining that a joint has a decreased range of motion, or finding an increase in joint size from periarticular fibrosis or osteophytosis. Plane or stress radiographs and arthrocentesis can confirm impressions from the clinical exam. However, it is critical to make a diagnosis of joint pain during the clinical exam and to confirm that OA is present and related to the pain with the assistance of radiographs. Although most would agree that the radiographic presence of OA increases the probability that a dog will have associated joint pain as stated before it is important to understand that the radiographic presence of OA, by itself, does not necessarily imply that a patient will have clinical signs of disease. It has been demonstrated in several reports that the relationship between the radiographic presence of OA and clinical symptoms is poor.3,4 In effect, radiographs are an excellent way to diagnose the presence of osteophytes and confirm a physical exam finding but are a poor indicator of the health status of the cartilage and/or the presence of inflammation.
The treatment of OA is either nonsurgical or surgical. Nonsurgical treatment should almost always be tried first and in many cases will be successful. For example, for the treatment of canine hip dysplasia, it was recently reported that all clinical symptoms resolved in approximately 50% of dogs treated nonsurgically. While OA is a slowly progressive disease there are undoubtedly inflammatory flares that can be managed medically. Nonsurgical management should focus on treatments where science provides evidence of efficacy. Many owners have limited financial resources so advice should be made to optimize those resources. First, dietary food intake restriction has been demonstrated to slow the onset and progression of OA in dogs with hip dysplasia.6 In that study, Labrador Retrievers that were fed 25% less food than what there litter mate day the previous day developed radiographic and clinical evidence of hip dysplasia later in life.6 I would suggest that in dogs are belong to a breed that is predisposed to orthopedic disease(s) or if they have a disease that will likely lead to OA (e.g. rupture of the cranial cruciate ligament, fragmented coronoid process, hip dysplasia) should be maintained at a body condition score of 4-5. If the dog is over weight, weight loss as a sole treatment has been demonstrated to provide significant relief and improve limb function in dogs with joint pain from OA. Daily activities like leash walks should be encouraged. Consistent, low load use of the limbs will not only provide the joint the range of motion which is needed to improve cartilage and synovial lining health but it will also assist in the management of the patient's body weight and begin the reverse disuse muscle atrophy that had developed. Swimming can also be very helpful. Specifically, aquatic therapy provides buoyancy (which eliminates ground reaction forces), multiplanar resistance to the muscles, and when dogs swim they use their joints with more flexion than during land based activities.8 Although it may be important for the patient to have exercise restriction this should be limited to when the joint is very painful during the early phases of treatment. In general, exercise restriction should also be limited to only a few days to a week and when the patient is "having a bad day".
Since treatment of inflammation is one of the primary ways to improve patient's suffering from OA we should have a basic understanding of the principal inflammatory pathways. Most clinicians first think of the arachidonic acid pathway when thinking of inflammation. This pathway can be further broken down into the cyclooxygenases (COX-I and COX-II) and lipoxygenases (LOX). One must be careful labeling all of the enzymes associated with any of these pathways as good or bad because while some enzymes in these pathways may act as mediators of inflammation and pain, others have important and necessary roles in the body. Most nonsteroidal anti-inflammatory drugs (NSAIDs) work to completely or selectively inhibit the cyclooxygenase pathway. The use of NSAIDs is a large component to the long term management of patient's suffering from OA. It is my opinion that when choosing an NSAID one can look at many things but the drugs ability to focus the effect on the COX-II isoenzyme should have a major role choosing a NSAID. The COX-I isoenzyme is constitutively expressed ad is responsible for several "housekeeping" physiologic functions. The inhibition of this isoenzyme by NSAIDs is associated with much of their related toxicity and adverse drug events (especially gastrointestinal side-effect). In contrast, the COX-II isoenzyme is inducible and is associated more with inflammation and pain. Inhibition of the COX-II isoenzyme is associated with much of the clinical benefits associated with the use of NSAIDs. While many NSAIDs are available over the counter there are several that have gained approval by the FDA for use in the dog for OA. In most circumstances, using an approved drug makes more sense than having a patient begin with an over the counter medication because the process of gaining FDA approval should provide some evidence of both safety and efficacy. Finally, while most NSAIDs can be used safely it is important to understand that they all risks and contraindications. While this will be discussed in detail understanding that most complications are related to the gastrointestinal tract in required and are avoidable. In one report of 29 dogs diagnosed with gastrointestinal perforation that were being treated with an NSAID the vast majority were prescribed a dose higher than the FDA approved dose and/or were concurrently treated with either a steroid or a second NSAID. Thus, understand that NSAIDs and steroids should be used independent of each other, the FDA recommended dose is recommended for a reason and owners need to be aware of these issues and the signs associated with early gastrointestinal side effect. I recommend that each NSAID prescription include a message to stop the use of the drug and contact a veterinarian if vomiting, diarrhea or a loss of appetite develops.
Additional aspects of nonsurgical management of OA in the dog that have scientific evidence of efficacy are prescription diets that are high in Omega-3 fatty acids. This approach attempts to substitute n6-derived eicosanoids, which for the most parts have vasoactive and proinflammatory effects with n3-derived eicosanoids which are less vasoactive and less proinflammatory. This concept is well supported in the human literature and there is some evidence on the veterinary side In one of those studies eighteen dogs were randomly assigned to three different isocaloric diet groups containing 21.4% fat (dry matter basis) differing only in their fatty acid composition: a diet with an n6-to-n3 fatty acid ratio of 28.0:1.0 (high-n6 diet), a diet with an n6-to-n3 fatty acid ratio of 8.7:1.0 (control diet), and a diet with an n6-to-n3 fatty acid ratio of 0.7:1.0 (high-n3 diet).11 Initially, the dogs were started on their assigned diet 3 months before surgical transection of the left cranial cruciate ligament, continued until surgical repair 6 months later, and maintained for an additional 12 months after repair. When compared with the high-n6 and control diets, consumption of the high-n3 diet was associated with lower serum concentrations of cholesterol, triglycerides, and phospholipids; lower synovial concentrations of prostaglandin E2; better ground reaction forces; and fewer radiographic changes of OA. Synovial membrane fatty acid composition mirrored the fatty acid composition of the diets consumed by the dogs. In the other scientific abstract,15 38 dogs with naturally occurring OA were placed on a commercially available therapeutic food formulated to contain an n6-to-n3 ratio of 0.7:1.0 (Prescription Diet J/d; Hill's Pet Nutrition, Topeka, Kansas) or a typical dry dog food. Limb function, as measured by force platform gait analysis, was measured at days 0, 45, and 90 and improved in the dogs fed the therapeutic diet when compared with the control diet.
There are several other nutritional supplements that can be considered. Two popular ones are chondroitin sulfate (CS) and green-lipped mussel (GLM). While there are many opinions regarding their efficacy and the literature includes some information supportive most independently performed research does not support a clinical benefit from these products. In one paper of 70 dogs with OA, dogs received either CS, GLM or a placebo. At the end of the study there was no benefit of either supplement when compared to dogs treated with placebo. Prevention or reversal of cartilage destruction is a proposed mechanism of action for these products. These agents, which historically have been called chondroprotective agents, are now more commonly referred to as disease-modifying osteoarthritis drugs (DMOADs). DMOADs are products that claim to prevent, reduce, or reverse cartilaginous abnormalities (principally by enhancing chondrocyte and synoviocyte metabolism). In addition, many products claim to have an anti-inflammatory effect by reducing mediators of inflammation in the joint. Orally administered polysulfated glycosaminoglycans (PSGAGs; e.g. Cosequin) are not regulated by the FDA, are considered nutritional supplements or nutraceuticals, and do not have an overwhelming amount of supportive evidence that they are effect in many clinical situations. However, they continue to be commonly prescribed by veterinarians and used by pet owners because they seem to be safe, are marketed well, there is easy access for owners and they have the potential to help. It is advertised that oral nutraceuticals provide the patient with a supraphysiologic concentrations of the precursors necessary for the synthesis of hyaline cartilage. Although most contain glucosamine and CS, scientific evidence supporting that these precursors reach the joint and help to form new hyaline cartilage is scarce. Some scientific information would suggest that Cosequin, when administered orally to Beagle dogs at a dose of 1500 mg of glucosamine and 1600 mg of chondroitin, is bioavailable. It was reported that after a single dose 12% of glucosamine and 5.0% of chondroitin was available. The bioavailability of chondroitin increased dramatically with longer term use. However, it is important to note that this reported blood concentration, not concentration in the target tissues. Another potential problem with nutraceuticals is that since there is no regulation of nutraceuticals the quality of the medication in the bottle is left up to the manufacturer. Some speakers have suggested that the actual concentration of glucosamine and chondroitin in these over-the-counter supplements varies widely. All of these concerns are also true for nutritional supplements that have been added to dog food.
Providing pain relief, independent of reducing inflammation, is another aspect managing OA. Tramadol is an analgesic and antitussive agent that has shown efficacy in humans and has gained in popularity in veterinary medicine. Tramadol its active metabolites exert their mode of action through opiate, adrenergic, and serotonin receptors. While it has seemingly has many potential advantages, the pharmacokinetics of the oral drug in the dog differs markedly from that in people with a much faster elimination 1/2 life and systemic clearance and a variable maximal plasma concentration. The drug can apparently be safely given but to the best of my knowledge evidence of a consistent analgesic effect in the dog is lacking with the available oral formulation. It is also important to consider the use of COX-II selective NSAIDs as potential analgesics. The topic of cyclooxygenase isoenzymes and pain is a popular one with literally hundreds of peer-reviewed manuscripts in the literature. While no uniform stance can be taken regarding the issue what can be said is that there is evidence that the COX-II isoenzyme is expressed in the dorsal horn of the spinal cord and that after peripheral injury or trauma its expression is upregulated. It has been suggested that inhibition of this enzyme by a COX-II selective inhibitor can provide analgesia in animal models. This has been demonstrated to be true in some human clinical investigations.
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