Startseite
Impressum
Datenschutz
 
arznei-telegramm 2006; 37: 28

 


GLUCOSAMINE (DONA 200-S) IN OSTEOARTHRITIS: BENEFIT STILL DOUBTFUL

Amino sugars such as glucosamine are synthesised from intermediates of glucose metabolism in all organs whenever required. They are regular components of proteoglycans of extracellular ground substance, e.g. cartilage. Glucosamine (DONA 200-S) is offered in Germany as a medicinal product and, internationally, also as a food supplement for the management of osteoarthritis. The theoretical basis for this indication is amongst other things derived from in-vitro findings, according to which proteoglycan synthesis may be stimulated in cartilage cell cultures (1,2). However, it has not been shown that orally ingested glucosamine actually reaches joint cartilage. Even in the serum, only a fraction of the concentrations used in vitro is needed following oral administration (3).

The marketing of chondroitin sulphate as a medicinal product for management of osteoarthritis is based on a similar concept ("joint nutrient"). Chondroitin sulphate is a long-chain polysaccharide and one of the main components of cartilage proteoglycans. It is not registered as medicinal product for the treatment of osteoarthritis in Germany, but as food supplement (e.g. in ORTHOEXPERT GELENKNAHRUNG).

The clinical benefit of both substances is controversial. In 2000, a meta-analysis of randomised, controlled studies compared the efficiency of glucosamine and chondroitin with that of placebo. The poor quality of the evaluated studies and hints of unpublished negative studies, however, question the validity of these findings (publication bias; a-t 2000; 31: 33-4) (4).

A recent systematic review (5) of the COCHRANE Collaboration does not find any effect on pain or on joint functions measured according to the WOMAC* score when the evaluation is restricted to randomised studies of higher quality. With no apparent justification, however, studies on a glucosamine preparation manufactured by the Italian company Rotta is separately evaluated in an "ad-hoc" sub-group analysis. The authors uncritically adopt the manufacturer's perspective claiming that Rotta's "crystalline glucosamine sulphate" displays "significant differences" compared with other glucosamine preparations such as glucosamine hydrochloride (6). The dubious positive results of this sub-group analysis are presented in the abstract but no reference is given to the relevant data used. For the primary end-point pain, an advantage is shown for the Rotta glucosamine preparation only in studies of poorer quality. The exception is a study presented only as an abstract (7) almost a decade ago, for which the manufacturer is said to have made additional data available to the COCHRANE authors. This study is the essential proof for an efficacy of glucosamine: it is large, allegedly of high quality and, as the only higher quality study covering all of the efficacy end points referred to in the review and with which it is evaluated, highlights positive results (5). There is just one snag in it - it is not publicly accessible and thus cannot be checked independently.

In February the eagerly awaited publicly financed US American study GAIT** (8) was published focusing on glucosamine and chondroitin sulphate. This is the biggest study of these products with over 300 patients per group. A total of 1,583 patients averaging 59 years presenting symptomatic osteoarthritis of the knee joint and radiologically confirmed osteophytes receive 500 mg of glucosamine hydrochloride three times daily, 400 mg of chondroitin sulphate three times daily, a combination of both, 200 mg of celecoxib (CELEBREX) or placebo for six months. The average pain score (WOMAC) of 236 is within the milder discomfort range (8).

Approximately 20% of patients in all groups dropped out of the study prematurely, most of them in the glucosamine group. The celecoxib group had the lowest number of dropouts. The primary end point is the response to treatment defined as a 20% decrease in the WOMAC pain score. There was an unexpectedly high placebo response rate of 60%, but no significant effect for glucosamine (64%), chondroitin sulphate (65%) and glucosamine plus chondroitin sulphate (67%). Also for the stringently defined response according to OMERACT-OARSI***, there was no significant difference between placebo and the test preparations whilst celecoxib significantly affected both end points (primary endpoint: 70%). Daily use of paracetamol (e.g. BEN-U-RON) increased by approximately half a tablet in all groups, from an average starting dose of 1 - 2 tablets of 500 mg per day. In the small sub-group of patients with moderate to severe pain, pre-defined by stratified randomisation, the 79% response rate under glucosamine and chondroitin sulphate was significantly higher than that observed with placebo (54%) (7). This result has to be interpreted with special caution as no significant effect was observed in these patients in the celecoxib group serving as the control (9). The authors expressly classify this as a finding from an "explorative" analysis that warrants confirmation in other studies (8).

Benefit from use of the amino sugar glucosamine (DONA 200-S) is not confirmed in osteoarthritis.
According to the WOMAC index glucosamine does not show a better effect on pain and function in randomised studies of higher quality published in full than placebo.
The benefit of glucosamine, chondroitin sulphate or a combination of both in patients with osteoarthritis of the knee joint remains unconfirmed in a recent study financed by public funds.
There are no valid data to corroborate an allegedly special position of Rotta's glucosamine preparation (DONA 200-S).

 

(R = randomised study, M = meta-analysis)

 

1

CHARD, J., DIEPPE, P.: BMJ 2001; 322: 1439-40

 

2

BASSLEER, C. et al.: Osteoarthritis Cartilage 1998; 6: 427-34

 

3

BIGGEE, B.A. et al.: Ann. Rheum. Dis. 2006; 65: 222-6

M

4

McALINDON, T.E. et al.: JAMA 2000; 283: 1469-75

M

5

TOWHEED, T.E. et al.: Glucosamine therapy for treating osteoarthritis. The Cochrane Database of Systematic Reviews 2006, Issue 1; Stand Febr. 2005

 

6

Rotta Pharmaceuticals: Health Claim Petition: Dietary Supplementation of Crystalline Glucosamine Sulfate; 23. Sept. 2003; http://www.fda.gov/ohrms/dockets/dockets/04p0060/04p-0060-cp00001-03-Original-Submission-vol1.pdf

 

7

ROVATI, L.C.: Osteoarthritis Cartilage 1997; 5 (Suppl. A): 72

R

8

CLEGG, D.O. et al.: N. Engl. J. Med. 2006; 354: 795-808

 

9

HOCHBERG, M.C.: N. Engl. J. Med. 2006; 354: 858-60


*

 

WOMAC-Index = Western Ontario and MacMaster Universities Osteoarthritis Index, Questionnaire to assess pain, function and stiffness in osteoarthritis

**

 

GAIT = Glucosamine/chondroitin Arthritis Intervention Trial

***

 

OMERACT-OARSI = Outcome Measures in Rheumatology Clinical Trials - Osteoarthritis Research Society International; For instance, response is defined as an improvement in pain or function of at least 50% and at least 20 mm on a visual analogue scale.



© arznei-telegramm 3/06