Glucosamine Sulfate and Chondroitin Sulfate

Osteoarthritis is the most common form of joint disease in the US. People are continually searching for the magic potion to postpone the inevitable problems of aging, symptoms of which dramatically effect the quality of our lives. Joint replacement has been a very successful treatment for the advanced stages, but no reliable and universally effective treatment exists for the early stages of osteoarthritis. Current approaches include: activity modification, weight loss, nonsteroidal anti-inflammatory medicines, exercise, cortisone injections and arthroscopic surgery. Recently there has been a surge of interest in the "chondroprotective" agents, glucosamine and chondroitin sulfate.

Glucosamine and chondroitin sulfate have been widely used in veterinary medicine for decades. They have also been used extensively on humans in Europe since the 1980’s without any observed side effects. To comprehend their potential benefit it is necessary to understand the biochemistry of normal articular cartilage.

The normal smooth, shiny surface cartilage that lines our joints is made up of cells called chondrocytes(5%), that are suspended in a softer matrix(95%). The chondrocytes make and maintain the matrix, which in turn provides a protected environment for the chondrocytes, in the face of the huge mechanical stresses we place on our joints with sports. Water comprises 70% of the matrix. The rest of the matrix is primarily collagen and proteoglycans. The proteoglycans are attached to a linear core protein(hyaluronan), giving the appearance of a "bottle brush". The proteoglycans that are important to cartilage contain the glycosaminoglycans chondroitin sulfate 4, chondroitin sulfate 6, and keratin sulfate. The proteoglycans are negatively charged and repel each other, but attract polar molecules so are therefore strongly hydrophilic. Thus explaining the high water content of the matrix. Bonds form between the glycosaminoglycans and the collagen fibers in the matrix. These bonds limit the amount of water that can be absorbed, by limiting the separation of the molecules. Without binding, the matrix absorbs excess water, the cartilage softens, and chondromalacia results. The surface cartliage has no intrinsic blood supply, so all nutrients must reach the chondrocytes by diffusion from the joint fluid or underlying bone. In summary, normal matrix is necessary for chondrocyte survival, and normal function.

The changes seen in the surface cartilage as a result of osteoarthritis are a complex interaction between the above macromolecules. For some reason in osteoarthritis, the chondrocytes produce a substance called interleukin-1, which starts a veritable cascade or release of other cytokines and prostaglandin derivatives. These in turn induce the chondrocytes to release lytic enzymes that destroy the collagen and proteoglycans. Decreased glycosaminoglycans, decreased bonding, and increased water content lead to softer cartilage that wears down faster.

Standard drug treatment of OA has been with NSAIDs and corticosteroids. Both are frought with potential complications. "Chondroprotective agents" are substances that stimulate chondrocyte production of collagen and proteoglycans, as well as synoviocyte productions of hyaluronan. They must also prevent cartilage degradation, and prevent fibrin formation and thus clotting in the subchondral bone and synovium. Glucosamine, chondroitin sulfate and hyaluronic acid are naturally appearing substances that possess some of these properties.

Normal chondrocytes make glucosamine from glucose. Supplying glucosamine provides the body with additional raw materials for matrix production. It has also been shown to increase the synthesis of proteoglycans and collagen by the chondrocytes. Glucosamine also has a mild anti-inflammatory effect unrelated to prostaglandin synthesis, possibly related to the scavenging of free radicals.

Chondroitin sulfate appears to inhibit many of the degradative enzymes that breakdown the cartilage matrix. It has also been found to prevent the fibrin thrombi in subchondral and synovial circulations. With aging the body produces less chondroitin sulfate and more keratin sulfate, which predisposes to the above thrombi.

Dosage: Glucosamine sulfate or hydrochloride 1500mg./day

Chondroitin sulfate 1200 mg./day

As opposed to NSAIDs which often show a decrease of symptoms within several days of starting the medication, glucosamine and chondroitin sulfate must be taken for at least a 30-60 day trial before judging their benefit in your particular case.

Complications and Risks: These nutritional supplements have been used extensively, and have a proven track record of safety. There are no known short term risks, and the National Institute of Health is currently studying the long term effect of using these products. We do not recommend their use in children or during pregnancy. If you have diabetes mellitus or are on coumadin, we recommend you consult with your physician before trying these products. Do not stop taking any of your other normally prescribed medications.

Purity and labeling: A recent University of Maryland study has found varying amounts of the above nutritional supplements, often far different than what is advertised of the bottle. We recommend that if you are going to use them, that you search for pharmaceutical grade products, that can be obtained by asking you local pharmacist.

authored by Bill Ferris MD, Mapleton Hill Orthopaedics 5/20/99