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Glucosamine Sulfate in Osteoarthritis: The Jury Is Still Out

Johannes W.J. Bijlsma; and Floris P.J.G. Lafeber
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From the University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands.


Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Johannes W.J. Bijlsma, Department of Rheumatology-Clinical Immunology, University Medical Center Utrecht, Postbus 85500, 3508 GA Utrecht, the Netherlands; e-mail, j.w.j.bijlsma@umcutrecht.nl.

Current Author Addresses: Drs. Bijlsma and Lafeber: Department of Rheumatology-Clinical Immunology, Unversity Medical Center Utrecht, Postbus 85500, 3508 GA Utrecht, the Netherlands.


Ann Intern Med. 2008;148(4):315-316. doi:10.7326/0003-4819-148-4-200802190-00012
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Treatment in osteoarthritis has 3 goals: relief of symptoms (pain), preservation of function (daily activities in life), and delay of joint damage (cartilage and bone) (1). Millions of patients with osteoarthritis use glucosamine. However, despite more than 4 decades of use and many controlled and uncontrolled trials, the effects of glucosamine on these outcomes are still unproven (2). One possible explanation is the lack of a standard preparation. The U.S. Food and Drug Administration classifies glucosamine as a dietary supplement and does not require standardization of its content and purity. An Italian company, Rottapharm, produces a standardized preparation that is the only one approved as a prescription drug for osteoarthritis (in the European Union).

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In Response
Posted on March 17, 2008
Jeremiah E. Silbert
Harvard Medical School
Conflict of Interest: None Declared

I do not agree that the "Jury is still out" in regard to the use of glucosamine sulfate in osteoarthritis. Prior to the current excellent negative clinical study that this Editorial accompanied as well as another recent negative clinical study of similar quality (1), we demonstrated that incubation of low concentrations of radiolabeled glucosamine with cultured cells (2) provided less than 1% of the galactosamine incorporated into chondroitin sulfate synthesized during the incubation. More than 99% was derived by cell production of unlabeled glucosamine from glucose. More recently we used varying concentrations of radiolabeled glucosamine with cultures of mouse (3) and human (4) chondrocytes to determine the percentage of radiolabeled glucosamine to unlabeled glucosamine incorporated into the chondroitin sulfate synthesized at different concentrations. We then measured serum glucosamine concentrations in human subjects following ingestion of 1500 mg of glucosamine sulfate (5). The exceedingly low concentrations that we found, averaging about 4 microM, were in the range that had generally provided only 1 or 2% of the galactosamine found in the newly-synthesized chondroitin sulfate of the cell cultures. This serum glucosamine level is about one tenth the glucose level achieved by comparable amounts of glucose ingestion, indicating that the glucosamine has mainly been utilized by the liver after its first pass from the gut through the portal system.

In conclusion, the concentration of glucosamine presented to cartilage or tissues other than gut or liver following oral ingestion is much too low to provide any increment in production or sustenance of cartilage chondroitin sulfate. The only possibility of action would have to be by providing some other stimulatory substance produced at these low concentrations or some action mediated by liver or gut where the concentration is much higher. Such actions have not been demonstrated at these low concentrations. The clinical studies confirm our previous conclusions that glucosamine sulphate is highly unlikely to have any usefulness in affecting joints.

1. Clegg DO et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795- 808.

2. Silbert CK et al. Production of [3H]hexosamine-labeled proteoglycans by cultures of normal and diabetic skin fibroblasts: dilution of exogenous [3H]glucosamine by endogenous hexosamine from glucose and other sources. Arch Biochem Biophys 1989;268:393-397.

3. Mroz PJ and Silbert JE. Effects of [3H]glucosamine concentration on [3H]chondroitin sulphate formation by cultured chondrocytes. Biochem J 2003;376:511-515.

4. Mroz PJ and Silbert JE. Use of [3H]glucosamine and [35S]sulfate with cultured human chondrocytes to determine the effect of glucosamine concentration on formation of chondroitin sulfate. Arth Rheum 2004;50:3574-3579.

5. Biggee BA et al. Low levels of human serum glucosamine after ingestion of glucosamine sulphate relative to capability for peripheral effectiveness. Ann Rheum Dis 2006;65:222-226

Conflict of Interest:

None declared

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