[en] BACKGROUND: Treatment of osteoarthritis is usually limited to short-term symptom control. We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms. METHODS: We did a randomised, double-blind placebo controlled trial, in which 212 patients with knee osteoarthritis were randomly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years. Weightbearing, anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years. Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis, whereas minimum joint-space width--ie, at the narrowest point--was measured by visual inspection with a magnifying lens. Symptoms were scored by the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. FINDINGS: The 106 patients on placebo had a progressive joint-space narrowing, with a mean joint-space loss after 3 years of -0.31 mm (95% CI -0.48 to -0.13). There was no significant joint-space loss in the 106 patients on glucosamine sulphate: -0.06 mm (-0.22 to 0.09). Similar results were reported with minimum joint-space narrowing. As assessed by WOMAC scores, symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate. There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups. INTERPRETATION: The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis.
Disciplines :
Rheumatology Public health, health care sciences & services
Author, co-author :
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Deroisy, Rita ; Université de Liège - ULiège > Médecine de l'appareil locomoteur
Rovati, Lucio C
Lee, Richard L
Lejeune, Eric ; Université de Liège - ULiège > Médecine de l'appareil locomoteur
Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Giacovelli, Giampaolo
Henrotin, Yves ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.) - Didactique des sciences de la santé - Pathologie générale et physiopathologie
Dacre, Jane E
Gosset, Christiane ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique : aspects généraux
Language :
English
Title :
Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial
(2000) American college of rheumatology subcommittee on osteoarthritis guidelines: Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum 43:1905-1915.
Dougados M. (1996) Recommendations for the registration of drugs used in the treatment of osteoarthritis. Ann Rheum Dis 55:552-557.
Altman R., Brandt K., Hochberg M., Moskowitz R. (1996) Design and conduct of clinical trials of patients with osteoarthritis: Recommendations from a task force of the Osteoarthritis Research Society. Osteoarthritis Cartilage 4:217-243.
Rashad S., Revell P., Hemingway A., Low F., Rainsford K., Walker F. (1989) Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 2:519-522.
Hamerman D. (1989) The biology of osteoarthritis. N Engl J Med 320:1322-1330.
Noack W., Fischer M., Förster K.K., Rovati L.C., Setnikar I. (1994) Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage 2:51-59.
Müller-Faßbender H., Bach G.L., Haase W., Rovati L.C., Setnikar I. (1994) Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage 2:61-69.
Rovati L.C. (1997) The clinical profile of glucosamine sulfate as a selective symptom modifying drug in osteoarthritis: Current data and perspectives. Osteoarthritis Cartilage 5(SUPPL. A):72.
McAlindon T.E., La Valley M.P., Gulin J.P., Felson D.T. (2000) Glucosamine and chondroitin for treatment of osteoarthritis: A systematic quality assessment and meta-analysis. JAMA 283:1469-1475.
Towheed T.E., Anastassiades T.P. (2000) Glucosamine and chondroitin for treating symptoms of osteoarthritis: Evidence is widely touted but incomplete. JAMA 283:1483-1484.
Adams M.E. (1999) Hype about glucosamine. Lancet 354:353-354.
Altman R., Asch E., Bloch D. (1986) Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee. Arthritis Rheum 29:1039-1049.
Dacre J.E., Huskisson E.C. (1989) The automatic assessment of knee radiographs in osteoarthritis using digital image analysis. Br J Rheumatol 28:506-510.
Byrne J., Heald G., James M.F., Kay M., Shorter J., Dacre J.E. (1993) Digital image analysis, a rapid and reproducible method for joint space measurement. Osteoarthritis Cartilage 1:60-61.
Lequesne M. (1995) Quantitative measurements of joint space width during progression of osteoarthritis: Chondrometry., Kuetter KE, Goldberg VM, eds. Osteoarthritic disorders. Rosemont, USA: American Academy of Orthopedic Surgeons; 427-444.
Bellamy N., Buchanan W.W., Goldsmith C.H., Campbell J., Stitt L.W. (1988) Validation study of WOMAC: A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833-1840.
Lequesne M., Brandt K., Bellamy N. (1994) Guidelines for testing slow acting drugs in osteoarthritis. J Rheumatol 21:65-73.
Piperno M., Hellio Le Graverand M.P., Conrozier T., Bochu M., Mathieu P., Vignon E. (1998) Quantitative evaluation of joint space width in femorotibial osteoarthritis: Comparison of three radiographic views. Osteoarthritis Cartilage 6:252-259.
Mazzuca S.A., Brandt K.D., Katz B.P. (1997) Is conventional radiography suitable for evaluation of a disease-modifying drug in patients with knee osteoarthritis?. Osteoarthritis Cartilage 5:217-226.
Lethbridge-Cejku M., Hockberg M.C., Scott W.W. Jr., Plato C.C., Tobin J.D. (1995) Longitudinal change in joint space of the knee: Data from the Baltimore Longitudinal Study of Aging. Arthritis Rheum 38(SUPPL.).
Neuhauser K.B., Anderson J.J., Felson D.T. (1994) Rate of joint space narrowing in normal knees and knees with osteoarthritis. Arthritis Rheum 37(SUPPL.).
Dieppe P.A., Cushnaghan J., Shepstone L. (1997) The Bristol "OA500" Study: Progression of osteoarthritis (OA) over 3 years and the relationship between clinical and radiographic changes at the knee joint. Osteoarthritis Cartilage 5:87-97.
Setnikar I., Cereda R., Pacini M.A., Revel L. (1991) Antireactive properties of glucosamine sulfate. Arzneimittelforschung 41:157-161.
Bassleer C., Rovati L.C., Franchimont P. (1998) Glucosamine sulfate stimulates proteoglycan production in human chondrocytes in vitro. Osteoarthritis Cartilage 6:427-434.
Dodge G.R., Hawkins D.F., Jimenez S.A. (1999) Modulation of aggrecan, MMP1, and MMP3 production by glucosamine sulfate in cultured human osteoarthritis articular chondrocytes. Arthritis Rheum 42(SUPPL.):253.
Sandy J.D., Gamete D., Thompson V., Verscharen C. (1998) Chondrocyte-mediated catabolism of aggrecan: Aggreganase-dependent cleavage induced by interleukin-1 or retinoic acid can be inhibited by glucosamine. Biochem J 335:59-66.
Buckland-Wright J.C., Wolfe F., Ward R.J., Flowers N., Hayne C. (1999) Substantial superiority of semiflexed (MTP) views in knee osteoarthritis: A comparative radiographic study, without fluoroscopy, of standing extended, semiflexed (MTP), and schuss views. J Rheumatol 26:2664-2674.
