What is it?
Osteoarthritis (OA), also called degenerative joint disease (DJD), is a common and painful disease in older humans and animals. OA mostly affects cartilage, the hard but slippery tissue that covers the ends of bones where they meet to form a joint. Healthy cartilage allows bones to glide over one another with little friction. It also absorbs energy from the shock of physical movement.
In osteoarthritis, the surface layer of cartilage breaks down and wears away, exposing the underlying bone. Bone rubbing against bone causes pain, and leads to inflammation, a complex response which contributes to further cartilage loss and discomfort. Over time, small deposits of bone – called osteophytes or bone spurs – may grow on the edges of the joint. Bits of bone or cartilage can break off and float inside the joint space. This causes more still more pain and damage.
Because animals cannot directly inform their caretakers of mild discomfort, the first signs of OA in veterinary patients are usually lameness and a reluctance to engage in normal activities. By the time such signs are noticed, the condition has usually progressed to moderate or severe disease. A diagnosis of OA usually requires a physical examination by a veterinarian, who can identify subtle signs of pain, osteophytes, and reduced range of joint motion. X-rays can also help identify DJD, though these are not always reliable indicators of discomfort or function.
The primary treatments for humans and animals with OA are weight loss, regular moderate exercise, and pain medications, typically the non-steroidal anti-inflammatory drugs (NSAIDs). There has also been interest among some health care providers in so-called nutraceuticals- substances derived from food sources that might treat the symptoms or alter the progression of OA.
Glucosamine is a substance found in joint cartilage and joint fluid. It is normally produced by the body from basic ingredients in food, and some is incorporated into joints. Though glucosamine is only one of the many building blocks of cartilage, it has been theorized that supplementing glucosamine orally might stimulate production or repair of cartilage. Some researchers have also suggested glucosamine might reduce inflammation in arthritic joints and thus reduce discomfort and slow the progression of the disease. Most supplement forms of glucosamine are derived from shellfish.
Chondroitin sulfate is another normal constituent of cartilage, and it has also been theorized to reduce inflammation and cartilage degradation in OA and perhaps to slow progression and improve comfort. Chondroitin in supplements is usually derived from cow cartilage.
Since glucosamine and chondroitin are categorized as nutritional supplements, they are not regulated by the Food and Drug Administration. Manufacturers do not have to prove that they are safe or effective in treating OA, and they do not have to abide by the strict quality control requirements for the production of approved drugs. Independent testing of over-the-counter glucosamine and chondroitin products have shown that they vary greatly in composition, and many do not actually contain the ingredients indicated on the label. Therefore, even if the substances have a role in treatment of OA, there is some concern that the actual preparations sold for humans and animals may not be of any value simply because they may not contain much of the ingredients.
Does It Work?
There has been a great deal of research on the effects of glucosamine and chondroitin on cells from joint tissues isolated in the laboratory. Though the results are inconsistent, some studies do show a number of actions on cells that might suggest a use for these agents in patients with OA, so the theory behind their use is plausible. However, there are other reasons for questioning whether these agents could actually work in a real patient.
For example, some controversy about whether oral preparations of chondroitin sulfate, which is a very large and electrically charged molecule, can be absorbed into the body and whether it actually get into joints affected with OA. Results of studies on the availability of oral glucosamine and chondroitin are extremely inconsistent, but generally show a low level of absorption in humans, rats, dogs, and horses. While some of the absorbed molecules do appear to reach affected joints, it is not clear if the amount is sufficient to have any effects. The amount that reaches the joints when the products are given orally is generally less than the amount used in the laboratory to demonstrate possibly useful actions on isolated cells and much less than the amount of glucosamine already circulating in the animal’s body.
Extensive clinical trials have been conducted in humans to determine if glucosamine and chondroitin can reduce symptoms or slow progression of OA. The best quality scientific studies require blinding, where the patients and researchers do not know whether each subject is getting the real treatment or a fake (placebo) treatment. And many other factors complicate interpretation of human clinical trials, so confidence in the results can only come from consistent, repeatable outcomes of numerous well-designed trials conducted by different investigators.
The results of these clinical trials are also highly inconsistent. In general, older studies with small numbers of patients and funded by supplement manufacturers showed some benefit from oral glucosamine and chondroitin. However, as larger, independently-funded trials with more subjects and better design have been published, the evidence has become predominantly negative.
The largest and best trial so far is the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a study comparing glucosamine and chondroitin, separately and together, against placebo and an NSAID (celecoxib, or Celebrex). Overall, the NSAID improved comfort and function significantly more than the placebo, while the various glucosamine and chondroitin products did not. Another study of many of the same subjects over 2 years did not find any significant difference in loss of joint space on x-rays (a measure of progression of OA) compared to the placebo. On balance, then, the evidence in humans suggests little to no benefit of these agents on symptoms or progression of OA.
There is very little research on the use of glucosamine and chondroitin in OA for veterinary patients. A recent review found only one good quality study comparing a combination glucosmine/chondroitin product to NSAIDs and placebo in dogs. In this study, the NSAIDs showed significant benefit on both objective and subjective measures of pain compared with placebo, but there was no difference between the placebo and the nutraceutical product.
Therefore, though there are some interesting effects of chondroitin and glucosamine on joint tissue in the lab, there are also questions about whether they could be effective in real patients. The balance of the clinical research evidence in both humans and animals does not suggest there is any real benefit of oral supplementation of these agents in patients with osteoarthritis.
Is It Safe?
Oral glucosamine and chondroitin supplements appear to be safe. There is some possibility that they may interfere with platelets, an element in the process of blood clotting. Alone, this does not seem to be of any clinical significance, but it is recommended that they not be used in patients already on anti-coagulant medications such as aspirin, clopidogrel (Plavix), or heparin.
There are also some concerns about glucosamine interfering with treatment for diabetes since it is structurally similar to sugar. In humans, this does not appear to be a real risk for diabetic patients. There is no research on this issue in veterinary patients.
Ø Glucosamine and chondroitin appear to have effects on joint tissues isolated in the laboratory that might indicate they could be useful adjuncts to osteoarthritis treatment if these effects also occurred in patients given oral preparations of these substances. However, there are reasons to question whether they could have such effects because they are poorly absorbed, and little of what is taken orally actually reaches affected joints.
Ø In humans, the largest and best clinical trials studying oral glucosamine and chondroitin supplements shows little to no effect on pain or on the degeneration of cartilage in patients with osteoarthritis.
Ø There is virtually no good quality research on the use of glucosamine and chondroitin in veterinary patients. The best study so far, done in dogs, found a combination of these agents to be of no benefit for patients with osteoarthritis. Further research in animals with osteoarthritis is warranted, but at this time the evidence does not support the use of glucosamine and chondroitin in these patients.
Ø Glucosamine and chondroitin taken orally appear to be safe in veterinary patients. However, they should not be taken by patients on anti-coagulant medications, and they should be used with caution in diabetics.
Ø The best treatments for osteoarthritis in veterinary patients, as in humans, are maintenance of a healthy weight, regular moderate exercise, and non-steroidal anti-inflammatory medications for pain
References and More Information
Aragon, C.L., Hofmeister, E.H., Budsberg, S.C., Systematic review of clinical trials of treatments for osteoarthritis in dogs. J Am Vet Med Assoc 2007; Feb 15;230(4):514-21.
Barker Bausell, R., Snake Oil Science: The Truth About Complementary and Alternative Medicine, Oxford University Press, 2007
Clegg, D.O., et al. Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis. N Engl J Med. 2006 Feb; 23;354(8):795-808.
Goggs, R., et al. Nutraceutical Therapies for Degenerative Joint Diseases:
A Critical Review. Crit Rev Food Sci Nutr 2005;45:145–164
Moreau, M., et al. Clinical evaluation of a nutraceutical, carprofen, and meloxicam for the treatment of dogs with osteoarthritis. Vet Rec 2003; 152:323-329
National Institute of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases. Handout on Health: Osteoarthritis 2006. http://www.niams.nih.gov/Health_Info/Osteoarthritis/osteoarthritis_hoh.pdf
Neil, K.M., Caron, J.P., Orth, M.W. The role of glucosamine and chondroitin sulfate in treatment for and prevention of osteoarthritis in animals. JAVMA Apr 2005;226(7);1079-1088
Sawitzke, A.D. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: A report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum 2008 Oct;58(10):3183-91
The Cochrane Collaboration, The Cochrane Reviews, a searchable database of systematic reviews of the human medical literature at http://www.cochrane.org/reviews/
© Brennen McKenzie, 2008