Glucosamine usage in treating Osteoarthritis

Role of Glucosamine in treating Osteoarthritis

By: Muhamad Na’im B Ab Razak

4^th year Medical Student, Orthopedic rotation.

University Science Malaysia

Glucosamine is an aminosacharide that function as a substrate for the biosynthesis of glycosaminoglycan that is important for the production of aggrecan and other proteoglycans of cartilage.

It also being demonstrated to reduce PGE2 production and interfere with nuclear factor kappa B (NFαB) DNA binding in chondrocytes and synovial cells [J.-Y. Reginster]. It also inhibits gene expression of OA cartilage in vitro.

However, it’s role in treating osteoarthritis remains controversy and debateable. The way on how the study being conducted is also questioned. Among the question that has being arised includes 1) early termination of study due to coast, 2) subject enrolled in the study has different degree of morbidity due to osteoarthritis, 3) different salt preparation for glucosamine (sulphate vs hydrochloride), 4) different result in study funded by pharmaceutical company which supports thebeneficial use of glucosamine and 5) do not know the exact mechanism of glucosamine sulphate intreating osteoarthritis.

However, glucosamine sulphate is proven beneficial when compared with placebo. Below are listed some conclusion of the latest study regarding the use of glucosamine.

There was evidence that glucosamine sulphate shows some clinical effectiveness in the treatment of OA of the knee. No trial data came from the UK and caution should be exercised in generalising the findings to the UK health-care setting. Cost-effectiveness was not conclusively demonstrated. There was evidence to support the potential clinical impact of glucosamine sulphate. The value of information analysis identified three research priorities: QoL, structural outcomes and knee arthroplasty. The biological mechanism of glucosamine sulphate and chondroitin remains uncertain and, in particular, the proposal that the active substance may be sulphate should be explored further.[Black C et al, 2009]

Glucosamine sulfate did not show a significant effect versus controls on minimum Joint space narrowing, JSN over the first year of treatment. However, after 3 years of treatment, glucosamine sulfate revealed a small to moderate protective effect on minimum JSN. The same was observed for chondroitin sulfate, which had a small but significant protective effect on minimum JSN after 2 years. This meta-analysis of available data shows that glucosamine and chondroitin sulfate may delay radiological progression of OA of the knee after daily administration for over 2 or 3 years.[ Lee YH et al, 2010]

Based on current evidence, the use of a combination product of glucosamine sulfate and chondroitin sulfate seems to have the greatest potential as a therapeutic intervention for patients at increased risk from the adverse events of accepted current oral therapies [Fox BA, 2009]

GS has shown positive effects on symptomatic and structural outcomes of knee OA. These results should not be extrapolated to other glucosamine salts [hydrochloride or preparations (over-the-counter or food supplements)] in which no warranty exists about content, pharmacokinetics and pharmacodynamics of the tablets.[J.-Y. Reginster]

It is controversial whether glucosamine sulphate is the first structure-modifying drug commercially available. Little evidence suggests that glucosamine is superior to a placebo treatment in restoring articular cartilage. [Kirkham SG]

There was no significant difference between glucosamine and placebo with respect to effects on pain, function, and range of movement [Conchrane review]

Glucosamine sulfate was not efficacious in treating the symptoms or retarding radiographic progression of hip OA over two years of use.[The John Hopkins Arthritis Center]

Large, randomized trials of glucosamine that lack pharmaceutical sponsorship have largely shown no effect of glucosamine for analgesia or structural modification in knee OA. One of the criticisms of the landmark GAIT trial in knee OA was that glucosamine HCL was used instead of glucosamine sulfate. Yet here, this difference appears to be irrelevant. One criticism of the trial presented here is that a large number of patients with mild radiographic disease were included. However, all patients were symptomatic, with baseline WOMAC pain and function scores consistent with other trials, and since the objective was to investigate radiographic progression, one would still expect patients with even mild radiographic OA to demonstrate differences in progression rates if there was a beneficial effect of the drug.[ editorial comment, The John Hopkins Arthritis Center]

My conclusion is, glucosamine can be used as a supplement nutrition for osteoarthritis patient. However, a clear instruction needs to be told to the patient that the role of glucosamine remains un-clear.

Reference

1) Black C, Clar C, Henderson R et al, "The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation.", Health Technol Assess. 2009 Nov;13(52):1-148, pubmed

2) Fox BA, Stephens MM., "Glucosamine/chondroitin/primorine combination therapy for osteoarthritis.", Drugs Today (Barc). 2009 Jan;45(1):21-31, PubMed

3) J.-Y. Reginster; O. Bruyere; A. Neuprez, Current Role of Glucosamine in the Treatment of Osteoarthritis", http://www.medscape.com/viewarticle/557058, accessed on 1 May 2010, 8.00 AM

4) Kirkham SG, Samarasinghe RK., " Review article: Glucosamine", Journal of Orthopaedic Surgery 2009;17(1):72-6.

5) Lee YH, Woo JH, Choi SJ, Ji JD, Song GG, "Effect of glucosamine or chondroitin sulfate on the osteoarthritis progression: a meta-analysis.",Rheumatol Int. 2010 Jan;30(3):357-63. Epub 2009 Jun 21, Pubmed

6) The John Hopkins Arthritis Center, "Is Glucosamine Sulfate an Effective Treatment for Osteoarthritis of the Hip? ",http://www.hopkins-arthritis.org/arthritis-news/2008/is-glucosamine-sulfate-an-effective-treatment-for-osteoarthritis-of-the-hip.html, accessed on 1 May 2010, 8.00 AM

7) Towheed TE, Maxwell L, Anastassiades TP et al, "Glucosamine therapy for treating osteoarthritis.", Cochrane Database Syst Rev. 2005 Apr 18;(2):CD002946.