Preventing osteoarthritis: What are the facts? (Proceedings)

Osteoarthritis affects diarthrodial joints of small animals including the shoulder, elbow, carpus, hip, stifle, tarsus, and spinal articulations. Once begun, the progression of the disease can only be slowed but never completely stopped.

One of the most common joints affected in both dogs and cats is the hip. Hip dysplasia is a genetic disease and dogs with it have increased incidence of disease in other joints. Expression of this genetic trait requires many genes to act in concert and the "right environment" while the animal is developing. To date, breeding programs have been able to reduce the incidence of hip dysplasia but not to eliminate it, likely because there are so many genes and other factors involved. Breeding programs aimed at reducing the incidence of hip dysplasia would benefit from the use of the dorsolateral subluxation score. This is a method of radiographing a dog's hips in a close to weight-bearing manner to simulate the joint laxity that would occur if a dog were standing. For detecting hip laxity in dogs as young as 8 months of age, this technique has reasonable sensitivity and specificity that may be better than orthopedic foundation for animals score or the Penn Hip distraction index. Until genetic markers are available, screening such as this is the only method available, and unfortunately, will not completely eliminate the disease in some breeds of dogs. Prevention through controlling the environment is the only other option for decreasing the incidence of hip dysplasia and osteoarthritis in other joints.

A recessive mode of inheritance has been identified in the Newfoundland for cranial cruciate ligament disease. Expression of CCL disease in Newfoundlands requires two copies of the mutant allele and an environment for expression of the disease as well. Therefore, only 51% of Newfoundlands with two mutant alleles for the gene actually develop a ruptured cruciate ligament. If we control environmental factors such as body condition score, housing conditions, neutering status, diet, etcetera, we can prevent rupture in dogs; even those with a genetic predisposition. This in turn could prevent secondary osteoarthritis in these dogs.

The options for preventing osteoarthritis then falls into several categories including diet, exercise or lifestyle, and nutraceutical supplementation.

Manipulation of the diet is available to pet owners as a method of prevention but requires strict adherence and compliance. Dogs of the same litter fed 25% less than ad libidum develop osteoarthritis in hip joints 50% less often than their free-fed littermates. These same dogs had 30% decrease in the incidence of shoulder osteoarthritis. In addition these dogs had a decrease in severity of, but not incidence of, elbow osteoarthritis. Labrador Retriever puppies from parents with hip dysplasia were also placed into two groups, either ad lib or 25% less food intake over their lifespan. The dogs fed ad lib developed radiographic signs of hip osteoarthritis at 6 years of age versus the restricted-fed dogs that developed radiographic signs at 12 years of age. Overweight dogs with hip osteoarthritis and hip pain have a significant decrease in lameness following weight reduction. Many believe that keeping dogs with osteoarthritis slightly underweight can help slow the progression and severity of osteoarthritis.

The type of activities the dog participates in can also affect the progression of osteoarthritis. Strength training can reduce the progression of osteoarthritis in human knees compared to passive range of motion exercises. Exercise can maintain muscle strength, which in turn helps stabilize the joint and slow the progression of osteoarthritis. The exercise must be controlled and continued indefinitely or the beneficial effects will not be long lasting. The appropriate exercise can decrease pain associated with mild to moderate osteoarthritis as well. By controlling the exercise, excessive force on the joint and articular cartilage is avoided while at the same time building muscle strength. Examples of controlled exercises include swimming, jogging or walking on non-slick surfaces such as grass lawns, and treadmills. Exercise to be avoided in dogs at increased risk of developing osteoarthritis include jumping, running on stairs, leaping, short fast stops after running, housing on slick surfaces, and play with other dogs that involves contact with the other dog while in motion. For example, dogs that fetch a ball can still do so after a joint injury, but the ball should be rolling slowly on the ground or stopped by the time the dog retrieves it. Rehabilitation and physical therapy exercises may also prevent further injury to injured joints.

Although the mechanism is not yet known, dogs that have undergone early sterilization (less than 5 months of age) may be at increased risk of developing hip osteoarthritis. The incidence of cranial cruciate ligament injury increases if the dog is spayed or neutered, regardless of the age of the patient when sterilization was performed.

Many nutraceuticals are on the market today and are too numerous to discuss here. We will focus on the more common agents only. Matrix metalloproteinases are enzymes that are increased in joints affected with osteoarthritis and their inhibition may slow the progression of degenerative joint disease. Arachidonic acid also increases within joints with osteoarthritis and is the precursor to prostaglandins including prostaglandin E2, a major mediator in pain and inflammation in the joint. Both of these proteins are decreased in the normal joints with oral administration of fish oil, specifically eicosapentaenoic acid. Eicosapentaenoic acid has been incorporated into several diets including Purina JM, Hill's j/d, and Eukanuba Senior Plus canine foods. Unfortunately, eicosapentaenoic acid did not decrease metalloproteinases or arachidonic acid in cranial cruciate ligament injured joints in dogs following surgical treatment The good news is that switching dogs to this diet following cruciate ligament injury in one stifle may be able to prevent rupture in the contralateral stifle. Although these diets may not prevent increased degenerative proteins in the joints of dogs following surgery, they can improve weight bearing and limb use in dogs with naturally occurring osteoarthritis. When a diet high in omega-3 fatty acids is fed to dogs prior to and after experimental cranial cruciate ligament transection and repair, the dogs have not only better ground reaction forces, but also fewer radiographic changes of osteoarthritis in their stifles.

Antioxidants such as vitamin E, vitamin C, and selenium have not been proven to definitively benefit humans or dogs with osteoarthritis and therefore are not recommended at this time. Methyl-sulfonyl-methane or MSM may improve function and decrease pain in humans but no clinical trials have been performed in dogs.

Glucosamine and chondroitin sulfate are components of normal joint cartilage and they may be able to rebuild damaged cartilage. A prospective double blind study of the effects of carprofen, meloxicam and Cosequin® (glucosamine, chondroitin sulfate) on ground reaction forces of dogs with established osteoarthritis found Cosequin had no effect and only carprofen and meloxicam improved lameness in the dogs. While these nutraceuticals may not decrease pain in osteoarthritis, they can decrease matrix metalloproteinases (believed to degrade cartilage in arthritis) and synovial membrane fibrosis which could slow the progression of the disease. In combination, gluscoamine and chondroitin may restore a more normal synovial fluid environment which could help prevent osteoarthritis. Different formulations of these nutraceuticals will have different bioavailability and this must be considered when recommending these supplements. As little as 50% of products on the market today meet their label claims. A recent review of osteoarthritis treatments found a moderate level of comfort for the effectiveness of glucosamine and chondroitin.

Polysulfated glycosaminoglycans (Adequan®) can protect articular cartilage from degradative enzymes as well as stimulate chondrocytes to produce normal components of articular cartilage and thus prevent osteoarthritis. Puppies from dysplasic parents given 5.0 mg/kg intramuscularly twice a week from 6 weeks to 8 months of age had a reduction in coxofemoral subluxation and improved Norberg angles (measure of hip joint congruity). Polysulfated glycosaminoglycans inhibit the intrinsic clotting system and can increase coagulation and buccal mucosal bleeding times. Conflicting reports exist as to whether or not polysulfated glycosaminoglycans are beneficial in slowing the progression of osteoarthritis, but the drug does appear to have a greater beneficial effect the earlier it is administered, and therefore, may be best as a preventative. A recent review of osteoarthritis treatments found a moderate level of comfort for the effectiveness of polysulfated glycosaminoglcans.

Pentosan sulphate is used similarly to polysulfated glycosaminoglycans and is a derivative of them. It can be given intra-articularly, intramuscularly, or subcutaneously and can decrease the amount of degradative products present in osteoarthritic cartilage. Given once weekly subcutaneously at 3mg/kg for four weeks following extracapsular repair of a ruptured cranial cruciate ligament, pentosan caused faster recovery of breaking ground reaction forces and decreased collagen degradation products if a partial menisectomy was performed. General observation of the dogs' gaits following surgery was not different from dogs given placebo injections and therefore, owners may not see the benefit of using this drug post-operatively. Further studies are needed to determine if the progression of osteoarthritis can be slowed long term in dogs with the administration of pentosan sulphate.

Hyaluronan is produced by chondrocytes and fibroblasts in articular cartilage and synovial fluid to act as a shock absorber and lubricant in the joint. Hyaluronan is given intra-articularly but lasts only a short time in the synovial fluid. Its effects are believed to last longer than its actual presence in the joint. Therefore, hyaluronan injection does not restore the normal concentration of hyaluronan in the joint nor does it reduce synovial fluid volume. Hyaluronan may decrease metalloproteinases, stimulate chondrocyte proliferation, and decrease degenerative cytokines such as tumor necrosis factor alpha and interleukin 1. Conflicting reports exist of hyaluronan's effectiveness at preventing or slowing the progression of osteoarthritis and, therefore, it's use cannot be definitively recommended at this time. High molecular weight with cross-linking may be a formulation with better efficacy and further study is needed.

Green-lipped mussel GLM has glycosaminoglycans and also acts as an anti-inflammatory through tetraenoic acid. Stabilized lipid preparations may decrease joint swelling and lameness but definitive studies on its effects do not yet exist.

P54FP is an extract of curcuma, a turmeric, and has been shown to decrease lameness but not peak vertical force on a force plate system. Again, further studies are warranted but its use may or may not help patients clinically.

Many methods are being investigated for the prevention of osteoarthritis including undenatured type II collagen (orally administered) and magnetic fields. Whether these methods will be beneficial is questionable and clearly, further extensive research in blinded clinical trials is needed. When considering recommending supplements, remember the quality of the preparation is extremely important and may not meet the label claims. Simply by keeping arthritic patients slightly lean and controlling the types of activities they participate in can help keep them active (and their owners happy) for a prolonged period of time.

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