To investigate the structural and symptomatic efficacy and safety of glucosamine in
knee osteoarthritis (OA).
DATA SOURCES:
Clinical trials of glucosamine were identified through electronic searches (MEDLINE,
EMBASE, BIOSIS, EMB review, the Cochrane Library) using the key words glucosamine,
osteoarthritis, degenerative joint disease, degenerative arthritis, osteoarthrosis,
gonarthrosis, knee, disease progression, and clinical trial. The bibliographic databases
were searched from their respective inception dates to August 2004. We also
hand-searched reference lists of relevant articles.
STUDY SELECTION AND DATA EXTRACTION:
Studies were included if they were double-blind, randomized, controlled trials that
evaluated oral glucosamine long-term treatment in knee OA; lasting at least one year;
and reporting as outcome measures the symptom severity and disease progression as
assessed by joint space narrowing. Two authors interpreted data independently.
Disagreements were resolved through discussion.
DATA SYNTHESIS:
Glucosamine sulfate was more effective than placebo in delaying structural progression
in knee OA. The risk of disease progression was reduced by 54% (pooled RR 0.46; 95% CI
0.28 to 0.73; p = 0.0011). The number-needed-to-treat was 9 (95% CI 6 to 20). The pooled
effect sizes for pain reduction and improvement in physical function were 0.41 (95% CI
0.21 to 0.60; p < 0.0001) and 0.46 (95% CI 0.27 to 0.66; p < 0.0001),
respectively, in favor of glucosamine sulfate. Glucosamine sulfate caused no more
adverse effects than placebo.
CONCLUSIONS:
The available evidence suggests that glucosamine sulfate may be effective and safe in
delaying the progression and improving the symptoms of knee OA. Due to the sparse data
on structural efficacy and safety, further studies are warranted.
CarrAJ. Beyond disability: Measuring the social and
personal consequences of osteoarthritis. Osteoarthritis
Cartilage1999; 7:
230–8.
3.
BuckwalterJASaltzmanCBrownTSchurmanDJ. The impact of osteoarthritis: Implications for
research. Clin Orthop Relat Res2004; 427S (suppl):
S6–15.
4.
LequesneMBrandtKBellamyNMoskowitzRMenkesCJPelletierJP. Guidelines for testing slow acting drugs in
osteoarthritis. J Rheumatol1994; 21 (suppl 41):
65–73.
5.
AltmanRDHochbergMMoskowitzRWSchnitzerJ, on behalf of the American College of
Rheumatology Subcommittee on Osteoarthritis Guidelines.
Recommendations for the medical management of osteoarthritis of the hip
and the knee. Arthritis Rheum2000; 43:
1905–15.
6.
HungerfordDSJonesLC. Glucosamine and chondroitin sulfate are effective
in the management of osteoarthritis. J Arthroplasty2003; 18:
5–9.
7.
BasleerCRovatiLCFranchimontP. Glucosamine sulfate stimulates proteoglycan
production in human chondrocytes in vitro. Osteoarthritis
Cartilage1998; 6:
427–34.
8.
BarclayTSTsourounisCMcCartGM. Glucosamine. Ann
Pharmacother1998; 32: 574–9. DOI
10.1345/aph.17235
9.
NoackWFischerMForsterKKRovatiLCSetnikarI. Glucosamine sulfate in osteoarthritis of the
knee. Osteoarthritis Cartilage1994; 2:
51–9.
10.
Muller-FassbenderHBachGLHaaseWRovatiLCSetnikarI. Glucosamine sulfate compared to ibuprofen in
osteoarthritis of the knee. Osteoarthritis Cartilage1994; 2:
61–9.
11.
RovatiLC. The clinical profile of glucosamine sulfate as a
selective symptom modifying drug in osteoarthritis: Current data and perspectives
(abstract). Osteoarthritis Cartilage1997; 5 (suppl A):
72.
12.
HughesRCarrA. A randomized, double-blind, placebo-controlled
trial of glucosamine sulphate as an analgesic in osteoarthritis of the
knee. Rheumatology2002; 41:
279–84.
RichyFBruyereOEthgenOCucheratMHenrotinYReginsterJY. Structural and symptomatic efficacy of
glucosamine and chondroitin in knee osteoarthritis. A comprehensive
meta-analysis. Arch Intern Med2003; 163:
1514–22.
15.
ReginsterJYDeroisyRRovatiLCLeeRLLejeuneEBruyereO. Long-term effects of glucosamine sulphate
on osteoarthritis progression: A randomised, placebo-controlled clinical
trial. Lancet2001; 357:
251–6.
16.
PavelkaKGatterovaJOlejarovaMMachacekSGiacovelliGRovatiLC. Glucosamine sulfate use and delay of progression
of knee osteoarthritis. A 3-year, randomized, placebo-controlled, double-blind
study. Arch Intern Med2002; 162:
2113–23.
17.
JadadARMooreRACarrollDJenkinsonCReynoldsDJGavaghanDJ. Assessing the quality of reports of
randomized clinical trials: Is blinding necessary?Control Clin Trials1996; 17:
1–12.
18.
HedgesLV. Distribution theory for Glass's estimator of
effect size and related estimators. J Educ Stat1981; 6:
107–28.
19.
RothmanKJ. Modern epidemiology.
Boston: Little Brown,
1986.
20.
CookDJSackettDL. The number needed to treat: A clinically useful
measure of treatment effect. BMJ1995; 310:
452–4.
21.
WhiteheadAWhiteheadJ. A general parametric approach to the metaanalysis
of randomized clinical trial. Stat Med1991; 10:
1665–77.
22.
SuttonAJAbramsKRJonesDRSheldonTASongF. Methods for meta-analysis in medical research.
Chichester, Great Britain: John Wiley
& Sons, 2000.
23.
DerSimonianRLairdN. Meta-analysis in clinical trials.
Cont Clin Trials1986; 7:
177–88.
24.
VajaradulY. Double-blind clinical evaluation of
intra-articular glucosamine in outpatients with gonarthrosis.
Clin Ther1981; 3:
336–43.
25.
VajaranetraP. Clinical trial of glucosamine compounds for
osteoarthrosis of knee joints. J Med Assoc Thai1984; 67:
409–18.
26.
ReicheltAForsterKKFischerMRovatiLCSetnikarI. [Efficacy and safety of intramuscular glucosamine
sulfate in osteoarthritis of the knee. A randomised, placebo-controlled, double-blind
study] German. Arzneimittelforschung1994; 44:
75–80.
27.
DasAJrHammadTA. Efficacy of a combination of FCHG49™ glucosamine
hydrochloride, TRH122™ low molecular weight sodium chondroitin sulfate and manganese
ascorbate in the management of knee osteoarthritis.
Osteoarthritis Cartilage2000; 8:
343–50.
28.
LefflerCTPhillipiAFLefflerSGMosureJCKimPD. Glucosamine, chondroitin, and manganese ascorbate
for degenerative joint disease of the knee or low back: A randomized, double-blind,
placebo-controlled pilot study. Mil Med1999; 164:
85–91.
29.
CohenMWolfeRMaiTLewisD. A randomized, double-blind placebo controlled
trial of a topical cream containing glucosamine sulfate, chondroitin sulfate, and
camphor for osteoarthritis of the knee. J Rheumatol2003; 30:
523–8.
30.
PujalteJMLlavoreEPYlescupidezFR. Double-blind clinical evaluation of oral
glucosamine sulphate in the basic treatment of osteoarthrosis.
Curr Med Res Opin1980; 7:
110–4.
31.
VazAL. Double-blind clinical evaluation of the relative
efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of
the knee in out-patients. Curr Med Res Opin1982; 8:
145–9.
32.
QiuGXGaoSNGiacovelliGRovatiLCSetnikarI. [Efficacy and safety of glucosamine sulfate
versus ibuprofen in patients with knee osteoarthritis] German.
Arzneimittelforschung1998; 48:
469–74.
33.
HouptJBMcMillanRWeinCPaget-DellioSD. Effect of glucosamine hydrochloride in the
treatment of pain of osteoarthritis of the knee. J
Rheumatol1999; 26:
2423–30.
34.
RindoneJHillerDCollacottENordhaugenNArriolaG. Randomized, controlled trial of glucosamine for
treating osteoarthritis of the knee. West J Med2000; 172:
91–4.
35.
BruyereOPavelkaKRovatiLCDeroisyROlejarovaMGatterovaJ. Glucosamine sulfate reduces osteoarthritis
progression in postmenopausal women with knee osteoarthritis: Evidence from two 3-year
studies. Menopause2004; 11:
138–43.
36.
BellamyNKirwanJBoersMBrooksPStrandVTugwellP. Recommendations for a core set of outcome
measures for future phase III clinical trials in knee, hip, and hand OA. Consensus
Development at OMERACT III. J Rheumatol1997; 24:
799–802.
37.
AbadieEEthgenDAvouacBBouvenotGBrancoJBruyereO. Recommendations for the use of new methods
to assess the efficacy of disease-modifying drugs in the treatment of
osteoarthritis. Osteoarthritis Cartilage2004; 12:
263–8.
38.
RavaudPGirardeauBAuleleyGRDrapeJLRousselinBPaolozziL. Variability in knee radiographing:
Implication for definition of radiological progression in medial knee
osteoarthritis. Ann Rheum Dis1998; 57:
624–9.
39.
CohenJ. Statistical power analysis for the behavioural
sciences. 2nd ed.Hillsdale, NJ: Lawrence Erlbaum
Associates, 1988.
40.
BruyereOHonoreAEthgenORovatiLCGiacovelliGHenrotinYE. Correlation between radiographic severity
of knee osteoarthritis and future disease progression. Results from a 3-year
prospective, placebo-controlled study evaluating the effect of glucosamine
sulfate. Osteoarthritis Cartilage2003; 11:
1–5.
41.
McAlindonTELaValleyMPGulinJPFelsonDT. Glucosamine and chondroitin for treatment of
osteoarthritis: A systematic quality assessment and meta-analysis.
JAMA2000; 283:
1469–75.
42.
HofferLJKaplanLNHamadehMJGrigoriuACBaronM. Sulfate could mediate the therapeutic effect of
glucosamine sulfate. Metabolism2001; 50:
767–70.
43.
HäuselmannHJ. Nutripharmaceuticals for
osteoarthritis. Best Pract Res Clin Rheumatol2001; 15:
595–607.
44.
SuttonLRapportLLockwoodB. Glucosamine: Con or cure?Nutrition2002; 18:
534–6.
45.
DealCLMoskowitzRW. Neutraceuticals as therapeutic agents in
osteoarthritis. The role of glucosamine, chondroitin sulfate and collagen
hydrolysate. Rheum Dis Clin North Am1999; 25:
379–95.
