Glucosamine and chondroitin sulfate are nutritional supplements widely used to treat osteoarthritis (OA). OA is articular inflammation characterized by progressive cartilage damage to the joints due to friction between bones. Osteoarthritis causes pain, stiffness, effusion, and deformity of joints.

The Roles of Glucosamine and Chondroitin in the Management of Osteoarthritis
Normal Knee and Knee Osteoarthritis

OA is the most common type of arthritis and is a major cause of limitation and decreased life quality in the age group above 50 years old. About 75% of patients aged> 65 years experience OA in joints. To date, there has been no ideal management in treating OA. Some treatments currently being pursued are aimed at easing pain and increasing the patient's functional abilities. OA treatment can be given pharmacologically, such as non-steroidal anti-inflammatory drugs and steroids, also nonpharmacological, such as physiotherapy, occupational therapy, weight loss, and physical exercise), alternative therapies (acupuncture), and surgical methods in severe OA.

At present, glucosamine and chondroitin are commonly used in the management of OA. Glucosamine and chondroitin potentially can act as chondroprotectors or "disease-modifying OA drugs." However, until now, the effectiveness of both is still in doubt.

Pharmacology and benefits of Glucosamine and Chondroitin

Glucosamine is an endogenous amino monosaccharide synthesized from glucose and used for glycoprotein and glycosaminoglycan biosynthesis. Glucosamine is abundant in connective tissue and is most abundant in cartilages. The chondroprotective effect of glucosamine is direct stimulation of chondrocytes and preventing degradation in the body through gene expression changes. However, until now, the exact mechanism of glucosamine in the body is unknown.

Chondroitin sulfate is a component of the extracellular matrix found in connective tissue, including cartilages, bones, skin, ligaments, and tendons. Chondroitin plays an important role in biomechanical cartilage, which is for resistance and elasticity. Chondroitin sulfate can act as an anti-inflammatory. In vitro, chondroitin sulfate can inhibit Cyclooxygenase (COX) -2, microsomal prostaglandin synthase (mPGES-1), and prostaglandin (PG) E2. Also, chondroitin can reduce proinflammatory cytokines, such as interleukin (IL) -6.

Rationalization of using Glucosamine and Chondroitin in Osteoarthritis Treatment

Glucosamine and chondroitin are believed to be useful for the management of osteoarthritis (OA). Glucosamine and chondroitin are considered to reduce pain and prevent or slow down cartilage damage. Some studies suggest that glucosamine can play a role in synthesizing glycosaminoglycans, proteoglycans, and hyaluronates in cartilage joints. They can also induce the synthesis of proteoglycans to form chondrocytes and inhibit the synthesis of metalloproteinases. Chondroitin sulfate acts as an anti-inflammatory to reduce inflammation that occurs in cartilages. Also, chondroitin can increase hyaluronic synthesis in synovial cells, type II collagen, and proteoglycans in chondrocytes. Chondroitin sulfate can also prevent oxidative stress, prevent apoptosis, and cartilage degradation.

To date, no significant side effects have been reported in the use of glucosamine and chondroitin. Glucosamine is derived from the shells of shellfish, such as lobster, shrimp. So, some people with shellfish allergies should not take glucosamine. Glucosamine and chondroitin are given orally. The usual glucosamine sulfate dose is 1500 mg/day, while the chondroitin dose is 800-1200 mg/day.

Clinical Evidence

The therapeutic efficacy of glucosamine and chondroitin has been extensively studied in various clinical trials in osteoarthritis (OA) patients. The effects of glucosamine and chondroitin are thought to reduce OA symptoms and disease modification, such as effects on organ structure or prevent further damage to the cartilage.

A meta-analysis involved 10 large randomized controlled trials (RCTs) examined the effectiveness of glucosamine, chondroitin, a combination of chondroitin and glucosamine in patients with genu or pelvic OA. In this meta-analysis, glucosamine, chondroitin supplementation, or a combination of both, did not significantly affect pain relief in OA compared to placebo. This meta-analysis also found that there were only minimal or no significant effects on reducing the joint gap's narrowing. This meta-analysis's heterogeneity and inconsistency are close to zero, so this meta-analysis's validity is quite good.

An RCT (Randomized Controlled Trial) was conducted by Sawitzke, et al., which involved 662 patients for 2 years. This clinical trial examined the efficacy and safety of glucosamine and chondroitin sulfate (monotherapy or combination) compared with celecoxib and placebo in patients with OA genu. This RCT got the same results as the previous meta-analysis. There were no clinically meaningful results for pain relief or function improvement in OA patients, according to the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). This RCT found an improvement in complaints in the initial 24 weeks of drug administration in all groups, but after that, there was no improvement during the two years of the study. This RCT was carried out for 2 years and was carried out by double-blinding. However, in this RCT, selective drop out is obtained so that it might cause refraction.

In a literature review involving various case series, RCTs, and meta-analyzes regarding the effectiveness of glucosamine and chondroitin in OA patients, glucosamine and chondroitin supplementation positively affect symptoms radiological findings. However, these effects are not clinically meaningful.

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