The maintenance of normal cartilage homeostasis requires the coordinated synthesis and degradation of articular cartilage
matrix macromolecules. If this balance in turnover is interrupted, matrix degradation is greater than chondrocyte replacement
of lost matrix. Ongoing, repetitive injury seems to be important to cytokine synthesis, and a shift in the balance between
proinflammatory and anti-inflammatory cytokines may contribute to the destructive process. Increased matrix synthesis in osteoarthritis,
which occurs in response to injury, doesn't appear to counterbalance matrix loss. This is particularly noticeable in the content
of proteoglycan, which decreases in osteoarthritic cartilage. As matrix metalloproteinases damage and deplete the collagen
fibril network, the remaining proteoglycans accumulate additional water in an unconstrained fashion, leading to increased
cartilage water content and cartilage swelling. Histopathologic changes characteristic of osteoarthritic articular cartilage
include irreversible chondrocyte loss from necrosis or apoptosis and chondrocyte cloning (a hallmark of osteoarthritic cartilage),
fragmentation of the cartilage surface, vertical clefts, bony remodeling at the joint periphery, and penetration of the tidemark
by blood vessels. Multiple tidemarks are progressive changes suggesting increasing severity. Osteophytes or enthesiophytes
seen on radiographs, at necropsy, and on histologic sections are often associated with osteoarthritis, but alone aren't sufficient
for such a diagnosis. From a biomechanical point of view, the causes of cartilage degeneration can be simplified to normal
loading on an abnormal surface or abnormal loading on a normal surface. Laxity or incongruity in the joint places the total
load over a smaller area of articular cartilage, thereby increasing the focal stress. The final result is cartilage thinning
caused by matrix loss, physical compression, fragmentation, and ulceration.5-9
Clinical presentation and risk factors
A diagnosis of osteoarthritis is made through clinical signs, physical examination findings, radiographic findings, and, occasionally,
synovial fluid analysis. The most common clinical sign is joint pain and associated lameness that may be acute or chronic
in dogs.10 Chronic pain resulting from osteoarthritis may be difficult to recognize, as it's frequently insidious in onset. This likely
scenario of undetected chronic pain is especially true in cats. Cats often present with a history of reduced appetite, weight
loss, reluctance to move, or failure to self-groom. Osteoarthritis should be on the list of differential diagnoses for cats
with these nonspecific complaints.2,10,11 Occasionally in both dogs and cats, more specific signs, including the refusal to jump or an overt limp, signal the presence
of pain. Regardless of historical findings, physical examination findings may include pain, crepitus, swelling, joint effusion,
periarticular fibrosis, muscle atrophy, and a decreased range of motion in the affected joints.10,11 All forms of joint disease, including immune-mediated disease, may have similar physical findings; therefore, the cause of
joint disease must be identified because the treatment varies accordingly. Radiographic osteoarthritic changes usually occur
relatively late in the disease process. These signs may include sclerosis of subchondral bone, osteophyte formation, periarticular
fibrosis, and joint effusion.12
The initial cause can be traumatic, mechanical, inflammatory, hereditary, or idiopathic. Identification and elimination or
modification of risk factors is one of the areas where we make the most headway in controlling osteoarthritis. Regardless
of the cause of injury, cartilage has a very limited ability for intrinsic repair, and current treatments for osteoarthritis,
although continuously improving, have substantial limitations. Most pathways to the development of osteoarthritis involve
developmental diseases with complex polygenic characteristics, rather than traumatic injury. And several other factors, such
as lifestyle, husbandry, environment, and the severity of the genetic disease, play an important role in the clinical expression
or outcome of each patient's condition.
Even when dogs are genotypically predisposed to osteoarthritis, evidence suggests that altering their environment can strongly
affect the phenotypic expression of the gene. Weight is one of the most important factors in phenotypic expression of osteoarthritis.
Seminal research reports describe the effects of limited food consumption on the incidence and severity of hip dysplasia in
Labrador retrievers over their lifetime.13-17 The most dramatic finding was that dogs fed ad libitum had significantly worse hip dysplasia than dogs offered 25% less food.
Similarly, research in cocker spaniels showed that dogs with cruciate disease and humeral condylar fractures were significantly
heavier than controls.18 In practice, we need to explain to pet owners that an increase in body weight and body condition score increases the likelihood
of dogs experiencing an injury or disease that predisposes them to osteoarthritis.18
Current osteoarthritis therapy is mainly palliative, aiming to reduce pain and maintain or improve joint function. Osteoarthritis
management should be thought of as a multi-step approach with three equally important components: weight reduction, exercise
and physical therapy, and pharmacologic management. Thus, initiating treatment requires a lengthy discussion with the client
about all management aspects. The veterinarian must examine each case carefully, assessing the age, normal activity levels,
and, most important, the owner's expectations for the animal's performance. Success largely depends on the accurate assessment
of these expectations.10
Weight control is a must when dealing with osteoarthritis. The vast majority of our patients with clinical manifestations
of osteoarthritis are obese. Owner education and proper dietary management must be considered in every case. In many cases,
weight reduction with rest and exercise modification diminishes or completely alleviates the clinical signs of osteoarthritis.
Using the joint in a manner that consistently causes discomfort accelerates cartilage destruction. Most patients with osteoarthritis
are comfortable with light to moderate exercise regimens that don't vary greatly. Enforced rest and exercise modification
should be individualized for each animal, but exercise peaks and valleys tend to exacerbate clinical signs. A good reference
documents physical therapy methods to help the osteoarthritis patient.19
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in treating osteoarthritis because of their ability to reduce pain—they
are the mainstay of chronic analgesia therapy in small animal medicine. The major weakness of these drugs is toxicity. Unwanted
side effects are especially problematic in cats. A wide variety of NSAIDs are now available; they decrease prostaglandin synthesis
by inhibiting the cyclooxygenase (COX) enzyme.20 At least three different COX enzymes exist (COX-1, COX-2, and COX-3) that are active in arachidonic acid metabolism, and
certain NSAIDs are selective in their actions against these isoenzymes.10 NSAIDs that selectively inhibit COX-2 and spare COX-1 will allow analgesia without the common side effects of COX-1 inhibition,
which include altered gastrointestinal and thrombocyte function. These newer products are potentially safer and as effective
in alleviating pain as older NSAIDs. In addition, extensive data show that many of the anti-inflammatory effects of NSAIDs
are incremental to the inhibition of arachidonic acid metabolism. Additionally, there is strong evidence that NSAIDs act directly
in the spinal cord and higher centers. The mechanisms of how the different COX isoenzymes are involved in generating painful
sensations aren't completely understood.10
By critically evaluating the current state of our treatment outcomes, we see a need to improve our effectiveness in treating
osteoarthritis pain. Clinical experience and experimental studies suggest that NSAIDs may not provide complete pain relief
in canine osteoarthritis.21-24 Thus, a multimodal approach for treating chronic pain may be the best approach for the future. Studies reveal the importance
of a constant input of noxious signals from the periphery in inducing changes in the central nervous system; such studies
are beginning to redirect our treatment methods.25 The nervous system is plastic and inputs from the periphery can activate various receptors and change the way nociceptive
signals are processed in the spinal cord.26,27 This cellular "windup" produces central sensitization through the activation of second messenger systems, the production
of nitric oxide and eicosanoids, and the induction of immediate early genes. Current research is actively looking into these
areas and may provide new treatment options in the near future.
Other than NSAIDs, there are few analgesics available that can be given chronically in the clinical setting. Compounds that
will be discussed act more indirectly than NSAIDs, either early in the inflammatory cascade or directly on the tissues themselves,
thus indirectly providing analgesic effects.10 Current research is directed toward compounds that are known as disease-modifying, or structure-modifying, previously called
chondroprotective agents. These drugs can affect both the inflammatory cascade and release of mediators and also the target
tissues (cartilage, bone, and synovium). The only disease-modifying drug licensed for veterinary use in the United States
is polysulfated glycosaminoglycan solution (Adequan®-Luitpold). Other products such as pentosan polysulfate and diacerhein,
which are approved in other countries, are currently undergoing additional testing to prove efficacy and safety in the United
States. There are many other drug classes, such as bisphosphonates and anticytokine compounds that may provide additional
options to help treat chronic osteoarthritis pain in the future.
Nutritional supplements of glucosamine and chondroitin sulfate are available. However, there is minimal scientific data available
for these products to prove clinical efficacy in osteoarthritis pain relief in the dog or cat. Another nutritional approach
that shows some promise is the use of long-chain omega-3 fatty acids. The most likely mode of action in the management of
osteoarthritis appears to be the inhibition of cytokines, eicosanoids, and other mediators in the complex inflammatory cascade.
1. Johnston, S.A.: Osteoarthritis: joint anatomy, physiology, and pathobiology. Vet. Clin. North Am. 27 (4):699-723; 1997.
2. Hardie, E.M.: Management of osteoarthritis in cats. Vet. Clin. North Am. 27 (4):945-953; 1997.
3. Moore, G.E. et al.: Causes of death or reasons for euthanasia in military working dogs: 927 cases (1993-1996). JAVMA 219 (2):209-214; 2001.
4. Kuettner, K.; Goldberg, V.M.: Osteoarthritis disorders. Rosemont: American Academy of Orthopaedic Surgeons, Rosemont, Ill.,
5. Pelletier, J.P. et al.: Etiopathogensis of osteoarthritis. Arthritis & Allied Conditions. A Textbook of Rheumatology, 14th Ed. (W.J. Koopman, ed.). Williams & Wilkins, Baltimore, MD, 2000; pp 2195-2245.
6. Lajeunesse, D.: The role of bone in the treatment of osteoarthritis. Osteoarthritis Cartilage 12 (Suppl A):S34-38; 2004.
7. Heingard, D. et al.: Biochemistry and metabolism of normal and osteoarthritic cartilage. Osteoarthritis. 2nd Ed. (K.D Brandt, et al. eds.) Oxford University Press Inc., New York, NY, 2003; pp 73-81.
8. Garnero, P. et al.: Molecular basis and clinical use of biochemical markers of bone, cartilage, and synovium in joint diseases. Arthritis Rheum. 43 (5):953-968; 2000.
9. Kühn, K. et al.: Cell death in cartilage. Osteoarthritis Cartilage 12:1-16; 2004.