Worldwide, osteoarthritis is the most common joint disorder. In western countries, radiographic evidence of this disease is present in the majority of persons by 65 years of age and in about 80 percent of persons more than 75 years of age.¹ Approximately 11 percent of persons more than 64 years of age have symptomatic osteoarthritis of the knee.²

With the continued growth of the elderly population in the United States, osteoarthritis is becoming a major medical and financial concern. Appropriate medical management requires that physicians be able to diagnose osteoarthritis early, recognize factors that may affect the prognosis or complicate the disease, and make effective use of the many available treatments.

Ideally, treatment of the disease involves relief of the symptoms, and controls the progressive degeneration of the articular joints. Modern drug therapy has concentrated on symptomatic relief of pain using simple analgesics such as aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. These drugs do not stop joint degeneration, and many are associated with side effects such as the production of potentially fatal stomach ulcers.

Glucosamine sulphate is a natural substance, termed a "chondroprotective agent", which relieves the symptoms of OA without serious side effects, and also appears to slow the progression of the disease

Biomechanical and biochemical forces are involved in cartilage destruction, which is at the core of osteoarthritis. Cytokines and growth factors are thought to play a role in the pathophysiology of the disorder. Interleukin-1 and tumor necrosis factor-b may function to activate enzymes involved in proteolytic digestion of cartilage.³ Growth factors such as tissue growth factor-b and insulin growth factor-1 may play a role in the body's attempts to repair cartilage through cartilage synthesis.⁴

When catabolism exceeds cartilage synthesis, osteoarthritis develops. Collagenolytic enzymes are thought to contribute to the breakdown of cartilage. Collagenase 1 (matrix metalloproteinase-1 [MMP-1]) is a fibroblast collagenase, and collagenase 2 (MMP-8) is a neutrophil collagenase. Collagenase 3 (MMP-13) may be particularly important because of its highly potent collagenolytic activity.³

 Glucosamine Sulphate Working Against Osteoarthritis

Osteoarthritis (OA) is the most common type of arthritis and typically damages the weight-bearing joints such as the hips, knees and spine.

Although primarily considered a disease of aging, OA can also result from sports-related injuries. In fact, about 10% of OA sufferers are in their 20’s. Figures from the Australian Bureau of Statistics reveal that more than 1.1 million Australians suffer from OA.

Ideally, treatment of the disease involves relief of the symptoms, and controls the progressive degeneration of the articular joints. Modern drug therapy has concentrated on symptomatic relief of pain using simple analgesics such as aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. These drugs do not stop joint degeneration, and many are associated with side effects such as the production of potentially fatal stomach ulcers.

Glucosamine sulphate is a natural substance, termed a "chondroprotective agent", which relieves the symptoms of OA without serious side effects, and also appears to slow the progression of the disease.

The Role Of Glucosamine

OA is caused by a degenerative process which affects the cartilage of the articular joints, resulting in symptoms of inflammation, pain and restricted movement. The degeneration appears to be caused by a disruption in the synthesis of important compounds (such as proteoglycans) from amino sugars within the chondrocytes (cartilage-producing cells).

Glucosamine is one of these amino sugars, and it is produced in the body from the sugar glucose and the amino acid glutamine through the action of the enzyme glucosamine synthetase.

Glucosamine stimulates the synthesis of proteoglycans, glycosaminoglycans (more commonly referred to as mucopolysaccharides), and collagen.

It therefore plays a role in the formation of cartilage and the cushioning synovial fluid between the joints, hence its "chondroprotective" classification.

The chondrocytes can either synthesize glucosamine themselves, or obtain it from circulating pre-formed glucosamine. Supplementary glucosamine can be an important source of this vital amino sugar for those with reduced capacity to produce glucosamine, such as the elderly.

Glucosamine Sulphate

Compared with other potential chondroprotective compounds such as chondroitin and animal cartilage, glucosamine is a much smaller molecule that is more readily absorbed and incorporated into cartilage and ligaments.

Glucosamine is available commercially as N-acetyl glucosamine, and the salts, glucosamine hydrochloride and glucosamine sulphate. Glucosamine sulphate is the form used in the majority of clinical studies - probably due to the stabilization of glucosamine with the sulphate ion.

Sulphur occurs throughout the body in amino acids, and occurs as sulfate in connective tissue as a binder and stabilizer. Sulphate is found in sulphated glycosaminoglycans and proteoglycans. Inorganic sulphate compounds have formed an important basis for Blackmores Celloid® Mineral therapy for over 60 years, with sulfate salts being used to help regulate body fluids and to stabilize intercellular connective tissue.

More recently, researchers at the World Health Organization’s Center for Rheumatology have discovered that sulphur inhibits the various enzymes which lead to cartilage destruction in joints.

The stabilization of glucosamine with sulphate appears to enhance the bio availability of glucosamine and potentiate its therapeutic effect.

Clinical Trials With Glucosamine Sulphate

Glucosamine sulphate is the most clinically studied glucosamine compound. It has been used in more than 20 double-blind, placebo-controlled studies involving over 6,000 people, together with hundreds of scientific investigations into its mode of action.

Several important studies have compared glucosamine sulphate with the drug ibuprofen in their effects on osteoarthritis. In one study of the knee OA, 200 patients were divided into two groups, one group taking 500mg glucosamine sulphate three times daily (1500mg daily dosage), the other ibuprofen 400mg three times daily. The study lasted four weeks and patients were assessed weekly according to a standard rating index of relief of symptoms of pain and improvement in mobility.

While improvement appeared sooner in the drug-treated groups in the first week, there was no difference in scores from the end of the second week onward. At the end of the treatment, there was a success rate of 52% in the ibuprofen group and 48% in the group taking 500mg glucosamine sulphate three times daily.

Significantly 35% of patients taking ibuprofen suffered side effects, mainly gastrointestinal, compared with only 6% in the glucosamine sulphate group. The researchers concluded that "glucosamine sulphate was therefore as effective as ibuprofen on symptoms of knee OA".

Several other similar studies compared the relative benefits and drawbacks of glucosamine versus ibuprofen for those suffering from OA. Those studies resulted in findings that while ibuprofen sometimes acted more quickly in the short term in reducing pain from OA, those taking glucosamine ultimately obtained greater and longer lasting pain relief from glucosamine. In addition, far more of the persons taking ibuprofen reported suffering negative side effects than did those persons taking glucosamine.

Of 355 patients screened, 212 were enrolled in the study and randomly assigned to receive glucosamine sulphate or placebo (figure 1). A similar number of patients in the two groups did not complete the 3-year treatment course: 38 of 106 (36%) in the glucosamine sulphate group and 35 of 106 (33%) in the placebo group (p=0·77), without significant differences in reasons for withdrawal. Patients in the two groups had similar demographic and baseline characteristics (table 1). Patients had similar mild to moderate osteoarthritis radiographic grading and joint-space widths at enrolment, with a degree of symptoms expressed by the WOMAC index that was also similar and of mild to moderate average severity. During the 6 months before enrolment, 51% of patients in both groups did not report any pharmacological treatment for osteoarthritis, whereas within the remaining patients 24% had received NSAIDs, 15% simple analgesics, 8% both NSAIDs and simple analgesics, 2% corticosteroids, without differences between groups. Compliance with study treatment was good: the proportion of patients who reported over 70% drug intake ranged between 81% and 91%, without significant differences between groups.

Figure 1: Trial profile

Characteristic  All randomised patients          Patients assessed for 3 years

                        Placebo (n=106)          Glucosamine sulphate (n=106)           Placebo (n=71)                Glucosamine sulphate (n=68)

:Most patients with osteoarthritis seek medical attention because of pain. The safest initial approach is to use a simple oral analgesic such as acetaminophen (perhaps in conjunction with topical therapy). If pain relief is inadequate, oral nonsteroidal anti-inflammatory drugs or intra-articular injections of hyaluronic acid­like products should be considered. Intra-articular corticosteroid injections may provide short-term pain relief in disease flares. Alleviation of pain does not alter the underlying disease. Attention must also be given to nonpharmacologic measures such as patient education, weight loss and exercise. Relief of pain and restoration of function can be achieved in some patients with early osteoarthritis, particularly if an integrated approach is used. Patients with advanced disease may eventually require surgery, which generally provides excellent results.