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Osteoarthritis and diet: Joined at the hip

Article

Osteoarthritis, also called degenerative joint disease, is the most prevalent joint disorder in dogs, affecting as many as 20% of adult dogs. Osteoarthritis is associated with inflammation and increased degradation or loss of proteoglycans from the extracellular matrix, resulting in a morphologic breakdown in articular cartilage.

Osteoarthritis, also called degenerative joint disease, is the most prevalent joint disorder in dogs, affecting as many as 20% of adult dogs.1 Osteoarthritis is associated with inflammation and increased degradation or loss of proteoglycans from the extracellular matrix, resulting in a morphologic breakdown in articular cartilage.2 There's no known cure for osteoarthritis, so treatment is focused on controlling pain, improving joint function, and slowing the degenerative process within the joint.3 Standard veterinary medical care typically involves weight management, controlled exercise, and anti-inflammatory and analgesic medications. In addition to medical therapy, dietary management can play an important role in the clinical management of dogs with osteoarthritis.

Weight management in osteoarthritis

Obesity, or excess body weight, results from consuming more calories than are needed to maintain a lean body condition. Obesity is recognized as a risk factor for osteoarthritis in both people and dogs. Preventing obesity can help reduce the incidence and severity of osteoarthritis.4-8 Excess body weight affects dogs from puppyhood through old age. When at-risk puppies were fed ad libitum, they exhibited an increased incidence and severity of hip joint laxity and hip dysplasia compared with puppies fed 25% less.9 Over time, those dogs fed to maintain lean body condition throughout their lifetimes exhibited a delayed need for treatment and reduced severity of osteoarthritis in the hips and other joints compared with their heavier siblings.6 (For additional information on the orthopedic aspects of this study, see the article by Dr. Gail Smith.) One of the most compelling findings from this study was the observation that even a mild degree of excess body weight can adversely affect joint health. This is important, since more than 25% of dogs seen by veterinarians are overweight or obese.10

The effect of obesity on osteoarthritis may be more than just physical strain due to weight bearing. Obesity is now recognized as an inflammatory condition; adipose tissue or associated macrophages produce inflammatory cytokines.11-15 C-reactive protein, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and other inflammatory mediators are elevated in the blood and adipose tissue of obese subjects, and are thought to contribute to many complications associated with obesity such as osteoarthritis.11,13,16-18 Obesity is also associated with an increase in oxidative stress.13,19

Multiple studies have shown that weight loss helps decrease lameness and pain and increase joint mobility in patients with osteoarthritis.5,20-22 Overweight dogs with coxofemoral joint osteoarthritis demonstrated decreased lameness (as measured by objective force-plate analysis and subjective clinical and client assessment) following weight reduction to ideal body condition.

In addition to dietary energy, dietary protein may play an important role in helping achieve and maintain ideal body condition. Protein has several physiologic effects that may benefit weight control: protein stimulates metabolism and protein turnover, induces thermogenesis, and promotes satiety.23-28 During weight loss and subsequent weight maintenance, increased protein intake promotes loss of body fat with retention of lean body mass.29-31 These aspects of protein may enhance weight loss in dogs with osteoarthritis.

Fatty acids in osteoarthritis

A primary target of osteoarthritis treatment is the inhibition of cyclooxygenase (COX) enzymes—especially the COX-2 enzyme—through the use of nonsteroidal anti-inflammatory drugs (NSAIDs).32-34 COX-2 selective inhibitors can decrease prostaglandin E2 (PGE2) concentrations and block inflammatory pathways involved in osteoarthritis, as well as reduce pain and lameness.32,33,35-38 Blocking both the COX and lipooxygenase (LOX) enzymes at the active sites of 5-LOX, COX-1, and COX-2 significantly reduces matrix metalloproteinases (MMPs), IL-1β, leukotriene (LT) B4, and PGE2, resulting in decreased tissue damage in arthritic joints.39

Another means of reducing PGE2 and inflammatory mediator production is through the use of dietary long-chain omega-3 (n-3) polyunsaturated fatty acids, especially eicosapentaenoic acid. The primary omega-6 fatty acid in cell membranes is arachidonic acid, which serves as the precursor for the production of the potent inflammatory mediators in osteoarthritis: PGE2, thromboxane (TX) A2, and LTB4. If the diet is enriched with long-chain n-3 polyunsaturated fatty acids—specifically eicosapentaenoic acid and docosahexaenoic acid—part of the arachidonic acid in cell membranes will be replaced by these n-3 fatty acids.40-42 Eicosapentaenoic acid may then be used instead of arachidonic acid for the production of eicosanoids, resulting in a different and less inflammatory set of compounds (e.g., PGE3, TXA3, and LTB5 instead of PGE2, TXA2, and LTB4).40,41 Dietary n-3 polyunsaturated fatty acids also suppress the proinflammatory mediators IL-1, IL-2, and TNF in cartilage tissue.43,44 Thus, substituting omega-3 for part of the omega-6 fatty acids should reduce inflammation and improve inflammatory conditions including osteoarthritis.

A review of studies in arthritic people indicated that most showed positive results from long-chain n-3 polyunsaturated fatty acid supplementation.45 Recent research in dogs supports many of these earlier findings in people confirming the clinical benefits of dietary n-3 fatty acids in osteoarthritis. Twenty-two dogs with osteoarthritis of the hip were given a fatty acid supplement marketed for dogs with inflammatory skin conditions (DermCaps—DVM Pharmaceuticals).46 When treated according to the manufacturer's recommended dosage, 13 of 22 dogs had noticeable improvement in their arthritic signs within two weeks.46 Another uncontrolled study evaluated dogs with naturally occurring osteoarthritis of the elbow and used force-plate analysis before and after dogs were fed a diet enriched with n-3 polyunsaturated fatty acids. Improvements in vertical peak force were observed within seven to 10 days on the diet (S.C. Budsberg: Unpublished data, 2004). In yet another study, dogs fed a diet enriched with n-3 polyunsaturated fatty acids following corrective surgery for ruptured cruciate ligaments showed a significant decrease in synovial fluid PGE2.47 Synovial fluid MMP-2 and MMP-9—enzymes which degrade structural proteins in cartilage—were also decreased in these dogs compared with dogs fed the control diet. (See the article by Dr. Mark Waldron for details on the role of n-3 fatty acids in osteoarthritis.)

Glucosamine in osteoarthritis

Glucosamine, an endogenously produced amino-sugar, is the principal component of the O-linked and N-linked glucosaminoglycans in connective tissues.48 A decrease in glucosamine synthesis by chondrocytes has been implicated in osteoarthritis, whereas supplemental glucosamine has a stimulatory effect on chondrocytes.49 Glucosamine is considered a chondroprotective agent and may minimize the progression of osteoarthritis.48,49

Several short- and long-term, double-blinded, randomized trials evaluating glucosamine supplementation in people with osteoarthritis of the knee were recently reviewed by meta-analysis.50 These studies documented significant improvement in clinical signs of osteoarthritis in patients consuming 1,500 mg of glucosamine per day (approximately 21 mg/kg ideal body weight). Two of these studies followed patients for three years and demonstrated that oral glucosamine inhibited the long-term progression of osteoarthritis.50 In addition to its effect on cartilage metabolism, glucosamine demonstrates anti-inflammatory effects on osteoarthritis.48 Clinical studies involving glucosamine alone in dogs are lacking. However, several in vitro and in vivo canine studies showed a benefit with glucosamine and chondroitin sulfate combinations.49,51 In studies involving arthritic people, glucosamine and chondroitin sulfate were equally beneficial and indistinguishable from one another in their effects.50

Antioxidants in osteoarthritis

Arthritis is associated with increased oxidative stress and chondrocyte-produced reactive oxygen species and decreased antioxidant capacity.52-56 The severity of arthritic lesions is increased in the face of decreased antioxidant capacity.56

In vivo studies have shown that exposure of chondrocytes to reactive oxygen species inhibits proteoglycan and DNA synthesis and depletes intracellular ATP.57,58 Reactive oxygen species contribute to cartilage degradation directly as well as by up-regulating the genetic expression of MMPs and decreasing production (or activity) of tissue inhibitors of metalloproteinases.57,59 In addition, oxidative stress induced chondrocyte senescence in vitro, with reduced glucosaminoglycan production and replicative lifespan—an effect that was reversible with antioxidant supplementation.56,60 Physiologic concentrations of vitamin E inhibited lipid peroxidation in chondrocytes and minimized oxidation-induced cartilage degradation in vitro.59 In a different model, vitamin C was effective at reducing premature chondrocyte senescence induced by reactive oxygen species.59

While limited in number, the published studies assessing in vivo benefits of antioxidants in osteoarthritis support the in vitro findings. A 10-year prospective cohort study showed that intake of supplemental vitamin E (P = 0.06), vitamin C (P = 0.08), and zinc (P = 0.03) independently reduced the risk for developing rheumatoid arthritis in elderly women.61 A two-year clinical trial in people with existing knee osteoarthritis evaluated the benefit of vitamin E supplementation on cartilage degradation.62 No statistically significant differences were observed in cartilage loss, most likely due to the small sample size. However, researchers detected directional differences with cartilage loss reduced in the vitamin E group compared with the placebo group. A one-year study in mice genetically predisposed to developing osteoarthritis also showed a benefit from dietary antioxidants.63 Glutathione peroxidase activity was significantly increased in both the serum and synovium of mice fed a complete diet supplemented with pyridoxine, riboflavin, selenium, and vitamins E, C, and A, confirming an antioxidant effect. The incidence of osteoarthritis in the antioxidant-supplemented mice was decreased by one-third to one-half.63 These various studies together strongly suggest a benefit of dietary antioxidants for patients with osteoarthritis.

Other nutrients in osteoarthritis

In addition to nutrient modifications that may help in the dietary management of dogs with osteoarthritis directly, dogs need appropriately balanced nutrition to support normal maintenance of joints and other tissues. Many people with arthritis appear to consume nutritionally imbalanced diets. Deficiencies in antioxidant nutrients, B-vitamins, zinc, calcium, magnesium, and selenium are frequently reported.64,65 While it's not known how many of these deficiencies contribute to osteoarthritis, these nutrients play a role in the normal maintenance of cartilage and other tissues. Therefore, it's important that dogs with osteoarthritis receive diets that provide complete and balanced nutrition.

Conclusion

Arthritis is an inflammatory condition that affects up to 20% of adult dogs. Feeding to achieve and maintain ideal body condition can minimize the clinical signs of osteoarthritis. In addition, a balanced diet formulated to contain a high amount of long-chain n-3 polyunsaturated fatty acids, a source of glucosamine, and abundant antioxidants may serve as a helpful adjunct to veterinary medical care.

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