Elsevier

The Lancet

Volume 357, Issue 9252, 27 January 2001, Pages 251-256
The Lancet

Articles
Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial

https://doi.org/10.1016/S0140-6736(00)03610-2Get rights and content

Summary

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 steoarthritis 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.

Introduction

Osteoarthritis is a major cause of disability and is among the most frequent forms of musculoskeletal disorders.1 The goal of pharmacological treatment is usually to control symptoms of the disease, pain, and limitation of function, which is traditionally accomplished by the use of analgesic agents or non-steroidal anti-inflammatory drugs (NSAIDs).2 Drugs for the treatment of osteoarthritis have been classified as symptom-modifying drugs and also as structure-modifying drugs if they are able to alter the joint structure favourably and thus actually interfere with the progression of the disease.3, 4 Although no drug can be included in the second category as yet, compounds are being searched for that may exert more specific effects than those of NSAIDs, directly interfering with some of the possible disease processes. Thus, these compounds might also favourably affect joint structure changes during long-term treatment, contrary to what has been observed with some NSAIDs that could even worsen progression.5

Glucosamine sulphate is the sulphate derivative of the natural aminomonosaccharide glucosamine. Glucosamine, a normal constituent of glycosaminoglycans in cartilage matrix and synovial fluid,6 could have various pharmacological actions in articular cartilage and joint tissues. Several short-term to medium-term clinical trials in osteoarthritis have shown the significant symptom-modifying effect of glucosamine sulphate and its good safety profile.7, 8, 9, 10 The need for long-term clinical trials with this compound has been emphasised.11, 12 We did a randomised double-blind placebo-controlled trial to establish whether glucosamine sulphate can affect progression of symptoms and joint structure changes in osteoarthritis.

Section snippets

Study design and selection of patients

We recruited patients from the outpatient clinic of the Bone and Cartilage Metabolism Research Unit of the University Hospital Centre in Liege, Belgium. Inclusion criteria were age over 50 years and primary knee osteoarthritis of the medial femorotibial compartment, diagnosed according to the clinical and radiological criteria of the American College of Rheumatology.13 Disease severity was graded on the basis of the Kellgren and Lawrence radiographic system.4 Major exclusion criteria were:

Patients

Of 355 patients screened, 212 were enrolled in the study and randomly assigned to receive glucosamine sulphate or placebo (figure 1). A similar number of patients in the two groups did not complete the 3-year treatment course:38 of 106 (36%) in the glucosamine sulphate group and 35 of 106 (33%) in the placebo group (p=0·77), without significant differences in reasons for withdrawal. Patients in the two groups had similar demographic and baseline characteristics (table 1). Patients had similar

Discussion

We have reported here that long-term administration of glucosamine sulphate over 3 years can prevent joint structure changes in patients with osteoarthritis of the knee with a significant improvement in symptoms.

Different validated methods have been proposed for measuring joint-space width from standardised radiographs, such as visual methods (using a caliper, ruler, or a magnifying lens) usually at the narrowest point of the joint, and computed readings of digitised radiographs, suggested to

References (29)

  • American college of rheumatology subcommittee on osteoarthritis guidelines: recommendations for the medical management of osteoarthritis of the hip and knee

    Arthritis Rheum

    (2000)
  • Dougados M for the Group for the Respect of Ethics and Excellence in Science: recommendations for the registration of drugs used in the treatment of osteoarthritis

    Ann Rheum Dis

    (1996)
  • D Hamerman

    The biology of osteoarthritis

    N Engl J Med

    (1989)
  • LC Rovati

    The clinical profile of glucosamine sulfate as a selective symptom modifying drug in osteoarthritis: current data and perspectives

    Osteoarthritis Cartilage

    (1997)
  • Cited by (1086)

    View all citing articles on Scopus
    View full text