The main goal of Osteoarthritis (OA) therapy should be to delay cartilage degeneration and even help to regenerate the cartilage structure.

The main goal of Osteoarthritis (OA) therapy should be to delay cartilage degeneration and even help to regenerate the cartilage structure

OA is a degenerative joint disease characterised by increasing loss of cartilage, remodelling of the periarticular bone, and inflammation of the synovial membrane.

It was long thought that only the cartilage is affected. However, it is now known that the underlying bone, as well as the synovium, also undergoes changes [1– 3]. The periarticular bone reacts with osteophyte formation which causes additional restriction in joint movement.

Due to disruption of the cartilage collagen matrix, the water content of the cartilage increases. Together with the progressive loss of proteoglycans, the elasticity of the cartilage diminishes. This is followed by a progressive loss of cartilage and the formation of osteophytes and calcium deposits. Osteophytes further limit flexibility of the joint. OA progression is associated with synovial inflammation, joint swelling, stiffness, and pain, leading to progressive functional impairment.

Common OA therapy focuses mainly on the treatment of symptoms, such as pain reduction, but does not treat the cause. However, the main goal of OA therapy should be to delay cartilage degeneration and even help to regenerate the cartilage structure. One approach in this direction is the treatment with chondroprotectives, differentiated in symptomatic slow-acting drugs in OA (SYSADOA) or structure modifying OA drugs (SMOAD).

A paper published in the International Journal of Rheumatology (Effects of Glucosamine and Chondroitin Sulphate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids) reviewed a number of studies to determine the ability of chondroprotectives to retard the degenerative process of cartilage destruction in OA with particular focus on glucosamine and chondroitin sulphate. The paper conclusively showed that the two mechanisms are able to slow the progression of cartilage destruction and may help to regenerate the joint structure, leading to reduced pain and increased mobility of the affected joint.

Treatment with chondroprotectives

Besides the common OA therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the treatment with chondroprotectives, such as glucosamine sulphate, chondroitin sulphate, hyaluronic acid, collagen hydrolysate, or nutrients, such as antioxidants and omega-3 fatty acids is a promising therapeutic approach.

Numerous clinical studies have demonstrated that the targeted administration of selected micronutrients leads to a more effective reduction of OA symptoms, with less adverse events. Their chondroprotective action can be explained by a dual mechanism:

  • as basic components of cartilage and synovial fluid, they stimulate the anabolic process of the cartilage metabolism;
  • their anti-inflammatory action can delay many inflammation-induced catabolic processes in the cartilage.


In vitro studies

According to the paper, in vitro studies on isolated chondrocytes, or cartilage explants from healthy or OA patients, provide much evidence for the proposed mechanisms regarding how glucosamine supports joint health. It has been shown that glucosamine enhances the production of cartilage matrix components in chondrocyte culture, such as aggrecan and collagen type 2 [4, 5]. Glucosamine increases hyaluronic acid production in synovium explants [6]. Further experiments have shown that glucosamine prevents collagen degeneration in chondrocytes by inhibiting lipoxidation reactions and protein oxidation [7]. MMPs (matrix metalloproteinases) and aggrecanases are the predominant cleavage enzymes in the cartilage. These enzymes are responsible for cleavage preferentially in the interglobular domain of the aggrecan molecule, which leads to loss of aggrecan function [8]. Glucosamine is able to inhibit the MMP synthesis, and further proteoglycan degeneration is therefore prevented [9, 10]. Glucosamine also inhibits aggrecanases by suppression of glycosylphosphatidylinositol-linked proteins [11]. Inflammatory processes, which are also responsible for degeneration of the cartilage, are inhibited by glucosamine.

Selected reviews and meta-analyses

Based on data from clinical studies, meta-analyses, and reviews on the effect of SYSADOA including glucosamine sulphate it was concluded that glucosamine sulphate, among others, has “demonstrated pain reduction and physical function improvement with very low toxicity, with moderate to high quality evidence” [12].

From the clinical trials, it can be concluded that long term treatment with glucosamine:

  • reduces pain,
  • improves function/mobility of the joint,
  • reduces OA progression,
  • reduces risk of total joint replacement.

Glucosamine has many favourable effects on cartilage. First, it has shown an anabolic stimulating effect on cartilage synthesis. Furthermore, it inhibits by means of several anti-inflammatory and antioxidant mechanisms, the catabolic cartilage degenerating reactions observed in OA. This can delay cartilage degeneration in OA which leads to a reduction in pain and swelling as well as to increased mobility of the affected joint.


Chondroitin sulphate (CS) is one of the natural glycosaminoglycans (GAG) composed of the alternating sugars D-glucuronic acid (GlcA) and N-acetyl-D-galactosamine (GalNAc). It is an important component of the extracellular matrix(ECM).CS is the most frequent GAG in the aggrecan molecule of the cartilage. Due to the negative charge of CS, it is responsible for the water retention of the cartilage, which is important for pressure resistance.

CS influences the symptoms of OA such as pain and inflammation, but also acts as a structure-modifying drug in OA (SMOAD). It may retard OA progression and could modify the course of OA.

The ability of CS to slow down the development of OA has been demonstrated in several clinical trials. [13, 14, 15]

Information from in vitro and in vivo studies, clinical trials, as well as meta-analyses lead to the conclusion that there is sufficient data to support the use of oral CS in OA. The findings show that CS reduces pain, improves function/mobility of the joint, and reduces the progression of OA by its structure-modifying effects.


Many clinical studies tested chondroitin sulphate together with glucosamine [16, 17,18–20]. The results suggest that both components may enhance each other’s efficacy. This synergistic effect was also proposed by various in vivo and in vitro studies [21, 22–25]. CS increases the hyaluronan production by human synovial cells, which has a beneficial effect on maintaining viscosity in the synovial fluid [26]. It has been shown that CS stimulates the chondrocyte metabolism, leading to the synthesis of collagen and proteoglycan, the basic components of new cartilage. Furthermore, CS inhibits the enzymes leukocyte elastase and hyaluronidase, which are found in high concentration in the synovial fluid of patients with rheumatic diseases. CS also increases the production of hyaluronic acid by synovial cells, which subsequently improves the viscosity and the synovial fluid levels.

In addition to their anti-inflammatory action, glucosamine and chondroitin sulphate exhibit an antioxidant action which leads to a significant reduction in iNOS expression and activity [27, 28]. This is one explanation why glucosamine and chondroitin reduce the otherwise NO-induced cell death of chondrocytes.


Based on the preclinical and clinical data, the review concluded that it is obvious that chondroprotectives such as glucosamine, chondroitin sulphate, and other nutrients, such as antioxidants and PUFAs, can modulate OA. In long-term use they exhibit, in contrast to NSAIDs, an excellent safety profile, with as few adverse events as placebo. The chondroprotectives are essential components of the cartilage metabolism and stimulate important cartilage regeneration processes, thereby adjusting the imbalance of catabolic and anabolic processes in OA. Newer data point out that inflammation and oxidative stress are characteristics of all stages of the disease.

Chondroprotectives are able to inhibit many of these processes. They defend chondrocytes against oxidative stress-induced apoptosis, reduce the inflammatory mediator-induced joint cartilage degeneration, and reactivate the inflammation reduced anabolic processes of extracellular matrix components. This leads to reduced inflammation, swelling, and pain, and to an increased mobility of the affected joints.

AUTHOR: Jörg Jerosch, “Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids,” International Journal of Rheumatology, vol. 2011, Article ID 969012, 17 pages, 2011. doi:10.1155/2011/969012