Management of osteoarthritis in sporting dogs (Proceedings)

Osteoarthritis (OA) 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. Approximately 20% of adult dogs suffer from osteoarthritis in one or more joints.

Genotype versus Phenotype

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” or phenotype 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 (CCL). Expression of CCL disease in Newfoundland's requires two copies of the mutant allele and an environment for expression of the disease as well. Therefore, only 51% of Newfoundland's 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 treatment of osteoarthritis can be divided into several categories including drugs, diet, exercise or lifestyle, nutraceuticals, and surgery.

Body weight

Restriction of caloric intake requires strict adherence and compliance from the owner. Canine obesity is as high as 41% of the population. Obesity and OA have long been linked, but evidence now suggests that obesity may be a direct cause of OA through adipokines like leptin and adiponectin. In humans, obesity has been linked to OA of the hands where excessive weight-bearing does not play a roll.

Genetically predisposed Labradors 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 a decrease in the severity of shoulder osteoarthritis. In addition these dogs had a decrease in severity of, but not incidence of, elbow osteoarthritis. 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.

Exercise

For many athletes, training keeps these dogs in excellent shape and rarely do they exhibit muscle atrophy. The type of activities the dog participates in, however, 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.17Exercise 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.18,19

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, and 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. Twice weekly physiotherapy sessions in a veterinary clinic along with weight loss and exercises performed at home reduces lameness in obese dogs with OA within 30 days of treatment. Rehabilitation and physical therapy exercises may also prevent further injury to injured joints.

For athletes daily exercises should include active range of motion exercise such as walking over cavaletti's 10 repetitions twice daily, sit to stands 15 in a row, down to sits 15 in a row, and potentially using elastic bands and walking for 15 to 20 minutes. Any exercise should encourage the dog to walk on the arthritic limb and use the affected joint within a normal range of motion without causing torsion or abnormal placement of the limb at any time.

Sex status

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.

Pharmacological agents

The following medications will be reviewed without respect to their potential for complications, however, when treating patients, one must consider the side effects of any treatment in the particular patient in question. Carprofen has been shown in several studies to induce improvement in the clinical signs of OA, with a moderate confidence that the results of the research could be extrapolated to our patients. Carprofen side effects include adipsia, anorexia, constipation, diarrhea, emesis, and polydipsia.

Meloxicam has been shown in five studies to be effective in the treatment of osteoarthritis, however, at least 12% of patients will experience gastrointestinal side effects, especially with chronic administration. Firocoxib has been shown to be effective at treating the pain associated with OA but the incidence of an adverse health event can be as high as 20%. Tepoxalin, a dual cyclooxygenase and lipoxygenase inhibitor, has not had any research studies to determine its effectiveness for the treatment of OA in dogs.

Tramadol is an opioid that possesses weak inhibition of opioid receptors along with interference with the release and reuptake of noradrenaline and serotonin in descending inhibitory pathways. In humans, tramadol in combination with an NSAID has been shown to be effective in the treatment of OA. Do not administer tramadol with a tricyclic antidepressant as this may cause serotonin syndrome producing behavior changes, neuromuscular hyperactivity, and autonomic activation. No studies have been done to evaluate its use in the treatment of OA in dogs.

Gabapentin blocks voltage-gated calcium channels and is beneficial in the treatment of neurogenic pain. No studies have been published evaluating the use of gabapentin for treatment of OA in dogs.

Amantadine inhibits N-methyl-D-aspartate (NMDA) receptors in the dorsal spinal horn where these receptors are activated with chronic pain via glutamate. Amantadine in combination with meloxicam has been shown to provide a greater effect than meloxicam alone for the treatment of OA in dogs. Although amantadine is not effective as a primary analgesic it may be beneficial if administered with an opioid.

Nutraceuticals

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 arachidonic acid and prostaglandin E2 are decreased in 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. These diets are capable of reducing lameness and improving the clinical signs of dogs with OA. In addition, switching dogs to these diets 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 following surgery.

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 CosequinÒ (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 slow the progression of 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 (AdequanÒ) 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 dysplastic 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.32Given 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. Some research has shown no effect while one study showed an improvement. 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, its use cannot be definitively recommended at this time. High molecular weight with cross-linking of hyaluronan 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. As part of a formulated diet, GLM has been found to have some benefit for OA dogs, however further study is needed.

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.  Rarely this nutraceutical can cause a malodor from the skin, urine and feces. Again, further studies are warranted but its use may help patients clinically.

Elk velvet antler has been shown in one objective placebo controlled study to improve weight-bearing in arthritic limbs of dogs. Two of 38 dogs developed Addison's disease, however, no other dogs were affected and it is unlikely related to the velvet antler.52There is moderately strong evidence that elk velvet antler is effective in treating OA.

Surgical treatment options

Degenerative joint disease that is a cause of significant and frequent pain and that has become refractory to medical management is treated surgically. The joint may be arthrodesed or the limb amputated. Alternatively, the joint can be replaced with a synthetic implant composed of stainless steel, high molecular weight polyethylene or titanium. The initial cause for the development of degenerative joint disease may vary but as long as there is adequate bone and normal conformation of the joint to accept the implant as well as soft tissue stability to hold the implant in place, various initial causes can be acceptable for joint replacement.

Replacement of the hip joint or total hip arthroplasty (THA) is performed as a salvage procedure in dogs with severe pain in one or both hips. Candidates for THA must have no other orthopedic disease in the limb that is to be operated as well as clients that are willing to perform the postoperative care necessary for a successful outcome. In other words, clients whose dogs undergo THA must be willing to restrict the dogs activity for several months (at least 2) after surgery, prevent them from infecting the incision postoperatively, and be willing to have their dog undergo a second surgery if complications develop.

Dogs that are not candidates for THA include those with orthopedic disease in the same limb, neurologic disorders such as intervertebral disk disease, lumbosacral disease, Wobbler's syndrome, or degenerative myelopathy. At the time of surgery they should be free of infections such as gingivitis, cystitis, otitis externa, pyoderma or other infections. If the patient develops a distant infection postoperatively, the owners must be vigilant enough to recognize it early and seek treatment as soon as possible. The patients are at an increased incidence of infection at the surgical site if the joint has been operated on previously or the patient is prone to distant infections that can spread hematogenously to the THA.

Two basic differences in THA exist in veterinary medicine, whether the implant is cemented in place or a cementless implant has been inserted with a press-fit. The press-fit technique avoids the use of the bone cement polymethyl methacrylate which, in theory, would decrease the incidence of aseptic loosening. Cemented implants have the benefits that they do not require extreme reaming of the femoral intramedullary canal and therefore would be less likely to develop fissure femoral fractures or subsidence postoperatively, work well in femurs that have a “stovepipe” isthmus as well as decreased cortical thickness.

Cementless implants have the benefits that they have a potentially decreased incidence of  infection, intrapelvic granulomas, and neuropathies. By 6 years postoperatively, 87% of  cementless implants are still intact and functioning well, which makes these implants a more attractive option for placement in younger dogs. German Shepherds, with their lack of narrowing of the femoral diaphysis (“stovepipe”) and relatively decreased cortical bone thickness are better candidates for a cemented implant in order to prevent complications such as subsidence and femoral fracture postoperatively.

Both types of THA have complications in common and include aseptic loosening of the implants (10-15% of human cases). With cemented implants the technique with which the cement was mixed and injected into the femur as well as the thickness of the cement mantle all affect the incidence and rate at which aseptic loosening develops. In recent studies cemented THA were analyzed post-mortem in dogs that had died for reasons unrelated to their THA. Implants without aseptic loosening were on average 5 years postoperative compared to 6 years in those implants with aseptic loosening.

This does not tell us definitively how long either a cemented or uncemented THA will last and that depends on many factors. For aseptic loosening, the development of wear debris increases the rate of aseptic loosening since the wear particles from the cup contact with the femoral head insight an inflammatory response and resorption of bone surrounding the implants. Larger acetabular cup sizes result in increased wear rates and wear debris so it follows that the larger the dog the faster wear debris and aseptic loosening will develop, however no clinical studies have proven this.

Aseptic loosening may be a more common occurrence in dogs that had femoral medullary canal infarction at the time of implantation. The incidence of infarction in dogs is 15% with cemented and cementless implants and 19.5% with the Zurich cementless hip. The Zurich cementless total hip system has become a common method of total hip arthroplasty and recent studies have followed dogs for up to 2 years postoperatively. There is a 17% complication rate including infection, femoral fracture, luxation (11%), cup loosening and implant failure or breakage. This system has the advantage that the acetabular cup can be adjusted because it is cementless and press-fit, in addition, aseptic loosening of a cup can be revised by implantation of a larger cup at any later date.66

Luxation of the THA is an uncommon occurrence, usually within the first month postoperatively, that most often requires a second revision surgery, sometimes a triple pelvic osteotomy is required to keep the implants seated. Careful surgical technique and prevention of increased activity postoperatively can prevent luxation. In addition, candidates for THA should not have severe muscle atrophy present at the time of surgery since atrophy increases the likelihood of luxation postoperatively.

Total elbow arthroplasty continues to be under development. The first system was semiconstrained, that is, capable of flexion, extension, pronation, and suponation to a limited degree. This system was then modified and has been used experimentally in healthy dogs as well as in dogs with severe degenerative joint disease of one or both elbows. This model has a successful outcome in 16/20 dogs but complications included fractures, infection, and luxation. This system is technically demanding and may be the reason it is not used more widely by veterinary surgeons. The latest total elbow system is a constrained system called the T.A.T.E. system and has been placed in approximately 10 dogs with very few complications to date.

There have not been any fractures or luxations and the system is less technically demanding to implant (personal communication, R. Acker). Unfortunately, there is no long-term data to support its use and it may fatigue quickly since it is so constrained, that is the dog can no longer supinate or pronate after the implants are placed. Therefore, this system should only be used in dogs with severe degenerative joint disease of the elbow that can no longer supinate or pronate the limb due to osteophytes and arthrosis in order to prevent early wear of the implants.

Much research still needs to be performed to determine the method for arthroplasty of the elbow in dogs and humans alike. The complex nature of the joint itself and the precision with which the humerus, radius and ulna interact make it one of the most unforgiving joints-one millimeter off and all function is lost.

Total knee replacement is still in the preliminary stages of development in dogs even though greater than 400,000 are performed every year on humans in the United States. Experimentally, dogs have been used as models for human implants. One recent study which involved 24 normal Hounds found that over a period of one year following cemented total knee arthroplasty only one dog had implant loosening (femoral) and 67% had excellent and the rest good joint stability. All dogs had resolution of lameness by 12 weeks postoperatively. A clinical study of 7 dogs was recently published by Liska, et al. In this report, all dogs had severe stifle OA and 2 were non-weight-bearing lame. These dogs were monitored for 1 year postoperatively and had cemented or a combination of cemented femur and cementless tibial implants.

One dog had no activity restriction following surgery and developed instability of the joint and subsequently infection and the limb was amputated 7 weeks postoperatively. The other 6 dogs steadily improved function over time, with significant improvements in function and gait by 6 months following surgery. If the dog had contralateral limb OA, they ended up placing more weight on the replaced knee limb than the contralateral limb. In the short term at least, total knee replacement will be a viable option for dogs and their owners, and may become an important option since the only other treatment for end-stage stifle joint disease is either arthrodesis or amputation.

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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