New Options for Old Problems - Relief from Arthritis
C. Denise Wall, PhD
A high percentage of dogs are affected by joint problems caused by osteoarthritis at some time in their lives. Common conditions that can result in painful arthritic changes and decreased function are hip dysplasia, ruptured cruciate ligaments in the stifle (knee), osteochondritis dissecans (OCD), spondylitis (a degenerative condition of the joints in the spinal column), joint injuries due to trauma, such as a kick from a cow, and the degenerative arthritis associated with old age. In the past, treatment for canine joint disease has been primarily limited to non steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, and steroids such as cortisone. Although these drugs may relieve the pain from the arthritis, they do not affect the underlying processes causing the pain. In addition, studies have shown these drugs can potentially make the condition worse in the long run. Recently, however, a new class of drugs and supplements have been successful in not only reducing the pain and increasing the function of arthritic joints, but also have the potential to arrest, reverse or prevent joint disease. These new drugs are the injectable polysulfated glycosaminoglycan (PSGAG), Adequan, and ingestible equivalents such as Cosequin and Glycoflex, oral supplements primarily consisting of glucosamine and chondroitin sulfate.
How Arthritis Occurs
The beginning of the process that leads to arthritis in the joint is usually one brought on by stress or injury to the joint. The stress or injury may be acute as in a kick or sustained over time as the result of wear and tear of age, poor structure or overwork for the dog’s physical condition. Whatever the cause, the cycle of destruction usually begins with an injury to the cartilage, the smooth cushiony covering of the opposing bones in the joint. This injured tissue causes destructive enzymes to be released into the joint. These enzymes cause further damage to the cartilage and also start to break down and thin the joint fluid that normally acts as a lubricant and cushion for the movements of the joint. As the cycle continues, the breakdown of cartilage and joint fluid causes more irritation, and a further release of destructive enzymes and inflammation, until finally, the bone underlying the cartilage starts to become damaged and remodel. At this stage the disease has become osteoarthritis, also know as degenerative joint disease (DJD). By this time the animal has usually started to feel pain and the degenerative changes in the bone will begin to show up in x-rays. To be truly effective in controlling further damage in DJD, a drug must break this cycle of inflammation and destruction. To understand how the new drugs and supplements came to be used to help canine arthritis, it helps to review some history of the use of these drugs in veterinary medicine.
Arthritis affects a large number of performance horses. As in dogs, for many years treatment was limited to alleviating the symptoms of the joint disease with NSA1Ds and corticosteroids. In the late 1970’s and early 1980’s, large animal veterinarians and scientists started experimenting with hyluronic acid, a primary component in joint fluid known to keep the joint well lubricated and functioning properly. Initially, hyluronic acid was injected directly into the problem joint. When this treatment proved successful in restoring joint function, other similar substances were tried. The most successful drugs contained a substance naturally occurring in the joint called glycosaminoglycan (GAG). The most promising of the new drugs was Adequan, a PSGAG. Eventually, it was shown that injection of Adequan into a muscle could yield good results and avoid the pitfalls associated with injecting drugs directly into a joint. Experimental studies proved that PSGAGs were absorbed from the muscle into the bloodstream and taken up in the joint in an effective form without breaking down the original components. Even more beneficially, it was demonstrated in several studies that PSGAGs were taken up preferentially by the diseased or inflamed joint. Other research uncovered the mechanism of the healing action of PSGAGs in the joint. First, PSGAGs stimulate the joint membrane to produce new joint fluid, which increases the thickness of the fluid and, therefore, the lubricating effect in the joint. Second, PSGAGs bind to damaged cartilage, stimulating healing and repair. It blocks the effects of degrading enzymes, which in turn blocks inflammation, destruction of cartilage, and breaking down of the joint fluid. These actions of PSGAGs in the joint help to break the destructive cycle of inflammation and degeneration.
These were promising findings with potential to improve the lives of many animals. As studies continued to define the biochemical interactions that made PSGAGs a possible long-term aid in the treatment of arthritis, individual’s reports of improvements in joint function of their horses with use of Adequan were generally positive. High performance sport horse owners embraced this new promising drug, regardless of the price, and it became widely used in large animal medicine in the mid to late eighties. Scientific studies soon confirmed the anecdotal reports that this therapy was indeed beneficial in many if not most horses with joint conditions. Most veterinarians reported at least moderate improvement in all types of horses. The most marked improvements, however, were reported by veterinarians whose primary client base was racehorses and other high performance sport horses.
As the success of Adequan grew, people started exploring the possibilities of an oral supplement that would accomplish similar benefits but without the hassle of an intramuscular (IM) injection. It was generally accepted that, unlike the injectable PSGAGs, an ingestable substitute would be broken down in the intestine and not absorbed and transported to the joint in the original form. Therefore, the oral food supplements were developed containing components that were considered building blocks involved in the assembly of GAGS that maintained healthy joints rather than the actual substances themselves. These new supplements usually contained glucosamine and chondroitin sulfate, as well as co-factors such as vitamin C and manganese that are needed for the efficient use of these substances by the body.
Eventually, the use of Adequan and the oral supplements started to spill over into small animal medicine. Reports of success were encouraging and in July of 1997, the U.S. Food and Drug Administration approved the IM use of Adequan Canine, the first approved disease modifying osteoarthritis drug for dogs. The oral glucosamines and chondroitin sulfate are considered food supplements and are not subjected to government monitoring of their use. Therefore, some veterinarians recommended the supplements long before Adequan was approved for use in dogs.
Which should I use?
The differences in effectiveness of the oral supplements compared to the injectable form of PSGAG will become more clear over time as more studies objectively evaluate the benefits of each. However, there are certain biochemical differences that are obvious, and while there are few well controlled studies to quantitate effectiveness, most of the scientific community would agree that the injectable PSGAGS are the most effective. The oral forms provide building blocks for GAG whereas the injectable PSGAG is already in the active form. In addition, it is likely that more GAG is made available to the joint from the injection.
One disadvantage to the injectable PSGAGS is the need for many clients to visit the vet for the treatments. The recommended treatment for a chronic arthritic problem is two shots a week for four weeks, then a shot every month or two thereafter. The treatment for an injury or as protection from arthritis after surgery, such as OCD surgery, may be limited to the initial four week course. The oral supplements, on the other hand, can simply be purchased from the vet’s office and given with the dog’s meal. Therefore, some may feel the ease of administration of the oral supplements outweighs the benefits of the injectable PSGAGs. The price of either is moderate, and well within most dog owner’s budgets.
As with any drug, side effects are present with Adequan, but they are generally limited to a mild “blood thinning” effect. PSGAG is a heparinoid, that is, similar to the blood thinner, heparin. However, this effect of PSGAGs is much milder and short lived than actual heparin. Because of this mild bleeding risk, it may be advisable to keep the dog from strenuous activity for several hours after the injection. Otherwise, PSGAGS and the oral supplements are both safe and effective and can even be used together to gain the maximum benefit.
As these new options become more widely accepted in small animal medicine, the conditions they may be used to treat will expand. Currently, they are being used in hip dysplasia (HD) to help provide relief from symptoms and slow the process of the inevitable joint degeneration that occurs in this disease. In most instances, one or both of these types of new drugs and supplements will provide some relief. However, it appears the benefit is greatest if the joint degeneration is still in the early stages. Therefore, it would serve dog owners well to have their dogs’ hips checked for HD early on before the disease has had a chance to progress. The functional life of the dog can be greatly prolonged by early detection and treatment. In fact, in one study, puppies at high risk for HD were given injections of Adequan at regular intervals from the age of eight weeks. These puppies were protected from developing HD compared to other puppies from control high risk litters not given Adequan. This study suggests that the development of HD in susceptible dogs can be prevented, or at least the onset of the disease delayed.
Other current uses of PSGAGs and the oral glucosamine/chondroitin sulfates are after joint surgeries or an injury to the joint. These types of acute trauma to the joint can initiate the inflammatory cycle that leads to DJD. Arthritis is a common long term complication from joint surgery that can be prevented or lessened by the early use of PSGAGs and/or glucosamine and chondroitin sulfate.
These new drugs and supplements have the potential to benefit dogs in general and particularly working dogs, extending their working life and improving their quality of life beyond what has been possible in the past. It may take several more years for these options to become well accepted in small animal veterinary practice. Typically, the higher functioning or working animals will have the benefit of the most advanced treatments in the field. Therefore, it helps to be abreast of the current literature in new treatments. More in depth information on these drugs and supplements can be obtained by reading the original scientific articles from the list of references (below) used to write this overview.
Adequan, Luitpold Pharmaceuticals, Inc., Shirly, NY – Package insert.
Altman, RD, DD Dean, OE Muniz, DS Howell : Therapeutic treatment of canine osteoarthritis with gylcosaminoglycan polysulfuric acid ester. Arthritis Rheum 1989, 32(10): 1300-1307
Budsberg, SC : Outcome assessment in clinical trials involving medical management of osteoarthritis in small animals. Vet Clin North Am Small Anim Pract 1997, 27(4):815-823
Canapp, SO Jr, RM Jr, McLaughlin, JJ Hoskinson, JK Roush, MD Butine : Scintigraphic evalation of dogs with acute synovitis after treatment with glucosamine hydrochloride and chondriotin sulfate. Am J Vet Res 1999, 60(12):1552-1557
Caron, JP, JB Kaneene, R Millar. Results of a survey of equine practitioners on the use and perceived efficacy of polysulfated glycosaminoglycan. J Am Vet Assoc 1996, 209(9):1564-1568
DeHaan, JJ, RL Goring, BS Beale : Evaluation of polysulfated glycosaminoglycan for the treatment of hip dysplasia in dogs. Veterinary Surgery 1994, 23, 177-181
Hamm, D, EW Jones : Intra-articular (IA) and intramuscular (IM) treatment of noninfectious equine arthritis (DJD) with polysulfated glycosaminoglycan (PSGAG). Equine Veterinary Science 1988, 8(6):456-459
Hamm, D, L Goldman, EW Jones : Polysulfated glycosaminoglycan: a new intra-articular treatment for equine lameness. Veterinary Medicine 1984 June:811-817
Kavangh, K, D Gelderman : Oral glycosamines: a survey of responses. Aust Vet J 1999, 77(4):220-221
Lippiello, L, A Idouraine, PS McNamara, SC Barr, RM McLaughlin : Cartilage stimulatory and antiproteolytic activity is present in the sera of dogs treated with a chondroprotective agent. Canine Practice 1999, 24(lss 1):18-19
Lust, G, AJ Williams, N Burton-Wurster, KA Beck, G Rubin : Effects of intramuscular administration of glycosaminglycan polysulfates on signs of incipient hip dysplasia in growing pups. Am J Vet Res 1992, 53:1836-43
Todhunter, RJ, G Lust : Polysulfated glycosaminoglycan in the treatment of osteoarthritis. JAVMA, 1994, 204(8):1245-1251
Walesby, HA, R Rosenbusch, LC Booth, CB Riley : Uptake and distribution of tritium-labeled polysulfated glycosaminoglycan in serum, urine, and superficial digital flexor tendon of rabbits after intramuscular administration. Am J Vet Res 2000, 61(1): 20-23
Copyright 2000. All rights reserved by C. Denise Wall.