The reverse glucosamine sulfate pathway: application in knee osteoarthritis

Glucosamine is a natural amino sugar and a normal constituent of glycosaminoglycans in the cartilage matrix and synovial fluid of joints. Crystalline glucosamine sulfate salt has been approved as a medicinal product for the treatment of osteoarthritis in several European countries. Nevertheless, although it has been prescribed for more than 10 years, it is only due to the research in the last 5 years that the scientific basis underlying its beneficial effects are starting to be clarified. In randomised, double-blind, placebo-controlled trials, this compound clinically controls pain and produces beneficial effects in patients with knee osteoarthritis, possibly delaying the appearance of long-term structural changes in the joint (i.e., it has a structure-modifying effect). Furthermore, it has an excellent toxicity profile. Despite the different lines of investigation that have been followed, the mechanism of action of glucosamine sulfate still remains to be clearly defined. However, the activity of glucosamine sulfate has recently been related to its capacity to downregulate the catabolic effects of pro-inflammatory molecules, such as IL-1, which are present in osteoarthritic cartilage.