Osteoarthritis is the most common cause of chronic pain in dogs with approximately one in five adult dogs having OA. OA (sometimes referred to as degenerative joint disease) is a slowly progressive degenerative disease involving the entire joint: articular cartilage, subchondral bone, synovial lining, joint fluid, ligaments, and muscles. Osteoarthritis is commonly classified as primary OA or secondary OA. Primary OA is associated with aging and chronic loading and wear of the articular surface. Secondary OA (the most common form seen in dogs) has many acquired and congenital etiologies including: ligamentous injury (CCL), abnormal joint conformation (elbow dysplasia), Osteochondrosis (OCD shoulder). In general, OA can develop in any joint where abnormal stresses are imposed on a normal joint or alternatively where normal stresses are imposed on an abnormal joint. Although more senior dogs exhibit clinical signs of OA as compared to their younger counterparts, younger dogs may also exhibit signs of OA. The most common example in younger dogs being OA associated with hip dysplasia. It becomes easy to understand why OA is painful when joint innervation and the role of inflammatory cytokines are considered.
Innervation of joints includes nociceptors which are free nerve endings found in all joint tissue except articular cartilage. They are found in the subsynovial layer only two to four cell layers beneath the synoviocytes lining the joint cavity. Dogs with OA have an ongoing synovitis the severity of which varies depending upon activity and joint trauma. The synovitis is accompanied by the accumulation of increased levels of eicosinoids (prostaglandins, leukotreines) and pro-inflammatory cytokines (IL-1, TNF, NO) in joint fluid. Additionally, synovitis is accompanied by increased vascular flow in the subsynovial tissue. These two factors, increased inflammatory mediators in the joint fluid and increased blood flow in subsynovial tissue, increases the exposure of free nerve endings (nociceptors) to inflammatory mediators. The result is sensitization of free nerve endings, increased stimulation of free nerve endings, and transmission of pain to the CNS. Inflammatory mediators also up regulate the expression of harmful mediaors which play a role in catabolism of articular cartilage.
The architect of cartilage is the chondrocyte which produces the extracellular matrix. The matrix is composed of glycosaminoglycans (hyaluronan and proteoglycan) and collagens (mainly type II). The collagen forms a dense network that retains the proteoglycan. The proteoglycan is highly charged and attracts water into the tissue. Thus cartilage is 75% water. In normal cartilage there is a very slow turnover of collagens but the proteoglycan is constantly being renewed. The proteoglycans are aggregated into large molecules ("aggrecan") with a protein core and many side chains of keratan sulphate and chondroitin sulphate. This core is in turn bound to hyaluronan chains with each chain containing many proteoglycan molecules. Aggrecan and water provide the compressive stiffness to the tissue whereas collagen provides the tensile strength. The morphological changes seen in OA include: 1. cartilage loss, especially in areas of increased load, 2. subchondral bone remodelling (loss of bone initially followed by sclerosis), 3. marginal osteophytosis, 4. variable synovial inflammation. The biochemical changes in the cartilage include: 1. loss of proteoglycan, 2.upregulation in the degradative and synthetic activities of chondrocytes, 3. disruption of the collagen network, 4. increase in water content. These changes reduce the elasticity of the cartilage leading to fibrillation and fissuring of the cartilage with eventual loss of tissue. If this continues eburnation of subchondral bone may result. It is proposed that the cytokines responsible for stimulating cartilage degradation in OA are interleukins 1 and 6 (IL-1 and IL-6) and tumor necrosis factor- (TNF-). However, whilst these cytokines have been shown to stimulate degradation in several species, their effect in the dog is less marked. Recent in vitro studies (Innes) on canine cartilage explants show the resisitance of canine cartilage to rhIL-1, rhIL-6 and rhTNF- However, canine cartilage does respond readily to oncostatin M (OSM) and Leukaemia Inhibitory Factor (LIF). Catabolic cytokines can stimulate the chondrocyte to produce and release degradative enzymes. The enzymes studied in most detail in this respect are the matrix metalloproteinases (MMPs) and the new family of endopeptidases the ADAM-TS-4 and -5 (A disintegrin and metalloprioteinase with a thrombospondin motif). ADAM-TS-4 and –5 are also known as aggrecanases. MMPs and aggrecanases can cleave the protein core of aggrecan so as to release the majority of the molecule from the matrix. Under normal circumstances the chondrocyte also produces a natural inhibitor of these enzymes known as tissue inhibitor of metalloproteinase (TIMP). TIMP production appears to be decreased in OA.
Osteoarthritis progresses slowly and has a gradual onset of clinical signs. Subsequently, the diagnosis of OA is often made in the later stages of the degenerative process after extensive bone and joint damage has occurred. Commonly the diagnosis of OA is made by radiographic changes characteristic of degenerative joint disease. However, by the time radiographic changes are apparent the condition has progressed considerably. Therefore, early intervention using alternative diagnostic modalities is essential for the well being of the animal. One recommendation is to establish an Osteoarthritis pain assessment screening protocol. Behaviors consistent with OA in dogs include: limping, inactivity, difficulty rising, lagging behind on walks, stopping on walks, difficulty posturing to eliminate. Managing the osteoarthritic dog is multifocal; An accurate diagnosis is essential for the management of secondary osteoarthritis since surgical intervention may be necessary to correct the underlying problem to achieve optimal outcome. In addition to appropriate surgical intervention, successful treatment of osteoarthritis is a compilation of strategies including client education, behavior modification (both client and pet), appropriate exercise activities, rest, weight control, disease modifying agents and anti-inflammatory medications. Of these, controlled exercise activity coupled with adequate rest and weight control will benefit your pet as much or more than any other modality.
Regular physical activity and rest play a key role in wellness. Episodic physical activity may also be preferable to continuous exercise by avoiding injury due to overuse. Episodic activity refers to those activities that occur for a reasonable time period multiple times throughout the day. Of considerable harm to the process of osteoarthritis is your pet having a sedentary life throughout the week only to exercise strenuously on the weekend. This lifestyle exacerbates the osteoarthritis and is very likely to result in serious injury. Treatment regimes should include regularly scheduled rest. Exercise effectively squeezes the water out of the cartilage making it less compliant and more susceptible to injury. Rest allows fluids to seep back into the cartilage restoring its mechanical efficiency and lessening the incidence of injury due to overuse. Family members must learn to recognize their pet’s body signals and know when to stop or slow down. Doing so prevents pain and injury caused by overexertion. Two types of exercise are important in osteoarthritis management. The first type, therapeutic exercises, keeps joints working as well as possible. Therapeutic exercises are low impact and designed to maintain or increase joint range of motion, proprioceptive feedback, muscle tendon unit and periarticular tissue elasticity. Examples of therapeutic exercises are passive range of motion activity, massage, aquatic therapy, and stretching. The other type of exercise, aerobic conditioning exercises, improves strength and fitness, and controls weight. Examples are brisk walking, brisk, walking or trotting through high grass, cavaletti training, and aquatic therapy. Your veterinarian and/or a rehabilitation therapist can evaluate your pet and develop a safe, personalized exercise program to increase strength and flexibility. Each program will include a warm up period, exercise period, and cool down period. Weight and body condition are important in preventing Osteoarthritis as well as an important factor in the treatment of osteoarthritis. Heavy dogs are at increased risk of developing arthritis because their joints may be strained by excess weight. This is especially evident in weight-bearing joints such as the knees and hips, which often show the first signs of weight-related strain and injury. An investigation into the cause of cranial cruciate ligament injury and the development of secondary osteoarthritis showed a significant risk factor to be obesity. One study in man showed that an average of 10 pounds of weight loss over a 10-year period decreased the risk of osteoarthritis of the knee by 50%. Similarly, obesity accounts for up to 30% of knee OA in man, exacerbates symptoms, and is associated with more rapid progression of the disease. If your pet is overweight and you enforce a weight loss program, you will dramatically decrease the risk of your pet injuring its knee joint and developing osteoarthritis. In fact studies of dogs with hip osteoarthritis show that reaching target reduction weight increases a dogs’ ability to move in a more normal fashion as assessed by gait analysis and owner observations.
Pain control medication allows the OA dog to engage in activity; this is turn helps control body weight and improve physical condition. The drugs of first choice for controlling arthritis are NSAIDs. NSAIDs function in part by inhibiting cyclooxygenase (COX) isoenzymes. COX-1 is the constitutive isoenzyme essential for the synthesis of homeostatic PGs in the GI tract, kidney, and platlets. COX-2 is for the most part induced and results in the production of PGs associated with pain and inflammation. However, COX-2 is also constitutive expressed and has a homeostatic role in canine brain, kidney, and vascular tissues. COX-3 is constitutively expressed and plays a role in brain tissue. NSAIDs approved for use in the dog include carprofen, deracoxib, etodolac, meloxicam, tepoxalin and others. All inhibit COX -1 and COX – 2 to varying degrees. The Coxib-class may exhibit less interference with the homeostatic functions of PGs associate with COX-1. However, the clinical effect of COX 1 vs COX -2 inhibition is largely unkown (Vioox!!)
Carprofen, a NSAID which is less ulcerogenic, is marketed by Pfizer Animal Health under their trade name Rimadylä. Rimadyl relieves pain and clinical signs of osteoarthritis in dogs, while causing less gastrointestinal side effects. Plasma and serum concentrations of carprofen are consistent throughout the treatment period. Serum concentrations peak at 2 hours, while synovial concentrations peak between 3-6 hours. The synovial concentration of carprofen ranges between 1-10 mg/ml during the treatment period in both normal and osteoarthritic joints. A significant reduction of PGE2 from chondrocytes occurs at all concentrations in this range. %). Recent studies have shown carprofen to have little effect on kidney and platelet function. Carprofen has been recently found to support cartilage metabolism and proteoglycan synthesis.
Etodolac (Etogesic) is a Fort Dodge product used for treatment of osteoarthritis in dogs. The drug is available as a non-chewable tablet and is administered at a dose of 10-15 mk/kg every 24 hours. Etodolac has been found to be an effective treatment for ameliorating the clinical signs of osteoarthritis. Side effects with etodolac are typical of that seen with the NSAID class of drugs, gastrointestinal ulceration being the most common problem. Gastrointestinal ulceration can be severe at dosages above the labeled dose- this is well documented in their label claim during toxicity trials. Conflicting data has been found on etodolac’s effect on proteoglycan synthesis and cartilage metabolism. The Cox 2:Cox 1 ratio appears to be less favorable as compared to carprofen.
Meloxicam was granted USDA approval in 2003, having been available in Europe since 1993. It is indicated for the control of pain and inflammation associated with OA in dogs. It is considered to have moderate COX-2 inhibition.
Deracoxib (Deramaxx) is a recently released NSAID from Novartis Animal Health approved for use in dogs for postoperative pain and inflammation. The recommended dose is 3-4 mg/kg, po, once daily for 7 days or 1-2 mg/kg, po, sid for chronic use. Like carprofen, deracoxib has a highly favorable Cox 1:Cox 2 ratio. The expected side effects are similar to other NSAIDS, primarily gastrointestinal disturbances.
The first dual-pathway (cyclooxygenase, lipooxygenase) canine NSAID, tepoxalin, has recently been approved. It has been suggested that the reduced ulcerogenic activity of tepoxalin is due to the ability to inhibit leukotriene production.
For many years, Aspirin was the most common NSAID used in the dog. Although effective in the majority of cases, aspirin is COX-1 selective causing platelet dysfunction and GI toxicity. Nevertheless, empirical observation would suggest that as many as 40% of pet owners administer aspirin to their pets. Even low dose aspirin causes GI lesions in dogs. However, dogs develop a tolerance to aspirin and lesions do not necessarily worsen. This has recently been explained by production of endothelial cell triggered lipoxin. Aspirin triggered lipoxin (APL) appears to be anti-inflammatory and decreases PMN migration to areas of ulceration. The production of APL is mediated through the COX-2 pathway. If aspirin is followed by or given concurrently with a COX-2 inhibitor, the APL pathway is blocked. Rather than APL production, a different pathway occurs giving rise to leukotriene B4 which is a very potent inflammatory cytokine. The result is a significant increase in GI ulceration. The clinical message is that one should not administer aspirin with a COX-2 inhibitor or administer a COX -2 inhibitor without adequate washout if aspirin has been used (10 -14 days).
Chondroprotective agents are emerging as a new class of drugs used to slow progression of and treat chronic DJD. These drugs not only should be antiinflammatory; but also should support anabolic (repair) processes in cartilage, bone and synovium essential for normalization of joint function. This class of drugs include the glycosaminoglycans. Examples of these drugs include glycosaminoglycan polysulfate ester, pentosen polysulfate and sodium hyaluronate. Cosequin (Nutramax Laboratories, Baltimore, MD) is marketed as a glycosaminoglycan enhancer, capable of providing raw materials needed for the synthesis of extracellular matrix of cartilage. Unlike most nutriceuticals, Cosequin has been evaluated in a variety of studies. Cosequin contains glucosamine which has been described as the building-block of the matrix of articular cartilage. It has been described as a preferential substrate and stimulant of proteoglycan biosynthesis, including hyaluronic acid and chondroitin sulfate. Cosequin also contains chondroitin sulfate, mixed glycosaminoglycans, and manganese ascorbate for the purpose of promoting glycosaminoglycan production. Orally administered glucosamine sulfate has been associated with relief of clinical signs of DJD and chondroprotection in clinical and experimental studies in man, horse and dog. Although glucosamine has a slower onset of relief of clinical signs associated with DJD as compared to ibuprofen, two clinical trials found it to have equal long term efficacy. No significant side effects have been reported with Cosequin.