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Glucosamine sulfate in osteoarthritis of the knee

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      Summary

      Glucosamine sulfate is a drug used for the treatment of osteoarthritis (OA), based on its pharmacological and metabolic activities on the cartilage and chondrocytes, complemented by mild anti-inflammatory properties and a favorable pharmacokinetic profile.
      The aim of this study was to define the activity and safety of glucosamine sulfate on the symptoms of patients with OA, using a multicenter, randomized, placebo-controlled, double-blind, parallel-group study design. The study included 252 outpatients with OA of the knee (Lequesne's criteria), radiological stage between I and III, and Lequesne's severity index of at least 4 points and symptoms for at least 6 months. Patients were treated with either placebo or oral glucosamine sulfate 500 mg t.i.d. for 4 weeks, with weekly clinic visits. Responders to treatment were defined as patients with a reduction of at least 3 points in the Lequesne's index with a positive overall assessment by the investigator.
      The Lequesne's index was 10.6±0.45 s.e.m. points in both groups at the start of the study. This decreased to 7.45±0.5 points in the treatment group (average 3.2) and 8.4±0.4 points in the placebo group (average 2.2) (P < 0.05, Student's t-test). The responder rate in the evaluable patients was 55% with glucosamine (N = 120) vs 38% with placebo (N = 121). These proportions were 52% vs 37% in an intention-to-treat analysis (P = 0.014 and 0.016, respectively; Fisher's Exact Test). The medications were well tolerated throughout the study, with no difference between the glucosamine and placebo treated groups.
      It is concluded that glucosamine sulfate may be a safe and effective symptomatic Slow Acting Drug for OA.

      Key words

      References

        • Batchlor EE
        • Paulus HE
        Principles of drug therapy.
        in: Moskowitz RW Howell DS Goldberg VM Mankin HJ Osteoarthritis: diagnosis and medical/surgical management. 2nd ed. WB Saunders, Philadelphia, PA1992: 465-492
        • Rashad S
        • Revell P
        • Hemingway A
        • Low F
        • Rainsford K
        • Walker F
        Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis.
        Lancet. 1989; 2: 519-522
        • Jimenez R
        Innovative therapeutic agents.
        in: Willkens RF Dahl SL Therapeutic controversies in the rheumatic diseases. Grune & Stratton, Orlando, CA1987: 213-251
        • Bird H
        The current treatment of osteoarthritis.
        in: Russel RGG Dieppe PA Osteoarthritis: current research and prospects for pharmacological intervention. IBC Ltd, London1991: 173-195
      1. (Suppl 1)
        • Lequesne M
        ILAR guidelines for testing Slow Acting Drugs in Osteoarthritis (SADOAs).
        in: Proceedings of the XVIIIth ILAR Congress of Rheumatology. Rev Esp Reumatol. 20. 1993: 220-221
        • Roden L
        Effect of hexosamines on the synthesis of chondroitin sulphuric acid in vitro.
        Arkh Kemi. 1956; 10: 345-352
        • Karzel K
        • Domenjoz R
        Effects of hexosamine derivatives and uronic acid derivatives on glycosaminoglycan metabolism of fibroblast cultures.
        Pharmacology. 1971; 5: 337-345
        • Vidal y Plana RR
        • Bizzarri D
        • Rovati AL
        Articular cartilage pharmacology. In vitro studies on glucosamine and non steroidal antiinflammatory drugs.
        Pharmacol Res Comm. 1978; 10: 557-569
        • Vidal y Plana RR
        • Karzel K
        Glucosamine: its role in the articular cartilage metabolism 2. Studies on rat and human articular cartilage.
        Fortschr Med. 1980; 98: 801-806
        • Bassleer C
        • Henrotin Y
        • Franchimont P
        In-vitro evaluation of drugs proposed as chondroprotective agents.
        Int J Tissue React. 1992; 14: 231-241
        • Setnikar I
        • Giachetti C
        • Zanolo G
        Absorption, distribution and excretion of radioactivity after a single intravenous or oral administration of [14C]-glucosamine to the rat.
        Pharmatherapeutica. 1984; 3: 538-550
        • Setnikar I
        • Giachetti C
        • Zanolo G
        Pharmacokinetics of glucosamine in the dog and in man.
        Arzneimittelforschung. 1986; 36: 729-735
        • Eichler J
        • Noh E
        Therapy of deforming arthrosis through the action upon the cartilagineous metabolism.
        Orthop Prax. 1970; 9: 225-229
        • Crolle G
        • D'Este E
        Glucosamine sulfate for the management of arthrosis: a controlled clinical investigation.
        Curr Med Res Opin. 1980; 7: 104-109
        • Drovanti A
        • Bignamini AA
        • Rovati AL
        Therapeutic activity of oral glucosamine sulfate in osteoarthritis: a placebo controlled double-blind investigation.
        Clin Ther. 1980; 3: 260-272
        • Mund-Hoym WD
        Medical treatment of spinal arthrosis with glucosamine or phenylbutazone. A controlled study.
        Therapiewoche. 1980; 30: 5922-5928
        • Pujalte JM
        • Llavore EP
        • Ylescupidez FR
        Double-blind clinical evaluation of oral glucosamine sulfate in the basic treatment of osteoarthrosis.
        Curr Med Res Opin. 1980; 7: 110-114
        • D'Ambrosio E
        • Casa B
        • Bompani R
        • Scali G
        • Scali M
        Glucosamine sulfate: a controlled clinical investigation in arthrosis.
        Pharmatherapeutica. 1981; 2: 504-508
        • Lopez Vaz A
        Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulfate in the management of osteoarthrosis of the knee in out-patients.
        Curr Med Res Opin. 1982; 8: 145-149
        • Lequesne MG
        Clinical features, diagnostic criteria, functional assessment and radiological classifications of osteoarthritis.
        Rheumatol Int. 1982; 7: 1-10
        • Weseloh G
        • Liebig K
        Therapeutic aspects in degenerative joint destruction.
        Orthopade. 1983; 12: 127-134
      2. Jäger M Wirth CJ Kapselbandläsionen: Biomechanik, Diagnostik und Therapie. Georg Thieme Verlag, Stuttgart1978
        • Kellgren JH
        • Lawrence JS
        Radiological assessment of osteoarthritis.
        Ann Rheum Dis. 1957; 16: 494-501
        • Lequesne MG
        • Mery C
        • Samson M
        • Gerard P
        Indexes of severity for osteoarthritis of the hip and knee. Validation-Value in comparison with other assessment tests.
        Scand J Rheumatol. 1987; 16: 85-89
        • Sander A
        Principles for the proper conduct of clinical drug trials (translated from Bundesanzeiger 243, 1987, p. 16617).
        Drugs made in Germany. 1989; 32: 21-23
        • Pocock SJ
        Protocol deviations.
        in: Pocock SJ Clinical trials: a practical approach. J Wiley, Chichester1983: 176-186
        • Bollet AJ
        Stimulation of protein-chondroitin sulfate synthesis by normal and osteoarthritic articular cartilage.
        Arthritis Rheum. 1968; 11: 663-673
        • Kalbhen DA
        • Karzel K
        • Domenjoz R
        A high molecular mucopolysaccharide peptide complex stimulating connective tissue metabolism.
        Pharmacology. 1968; 1: 33-42
        • Nevo Z
        • Dorfman A
        Stimulation of chondromucoprotein synthesis in chondrocytes by extracellular chondromucoprotein.
        in: Proc Natl Acad Sci USA. 69. 1972: 2069-2072
        • Stancikova M
        • Trnavsky K
        • Keilova H
        The effect of antirheumatic drugs on collagenolytic activity of cathepsin B1.
        Biochem Pharmacol. 1977; 26: 2121-2124
        • Baici A
        • Salgam P
        • Fehr K
        • Boni A
        Inhibition of human elastase from polymorphonuclear leucocytes by a glycosaminoglycan polysulfate (Arteparon).
        Biochem Pharmacol. 1980; 29: 1723-1727
        • Adam M
        • Krabcova M
        • Musilova J
        • Pesakova V
        • Brettschneider I
        • Deyl A
        Contribution to the mode of action of glycosaminoglycanpolysulphate (GAGPS) upon human osteoarthritic cartilage.
        Arzneimittelforschung. 1982; 30: 1730-1732
        • Burkhardt D
        • Ghosh P
        Laboratory evaluation of antiarthritis drugs as potential chondroprotective agents.
        Semin Arthritis Rheum. 1987; 17: 3-34
        • Altman RD
        • Dean DD
        • Muniz OE
        • Howell DS
        Prophylactic treatment of canine osteoarthritis with glycosaminoglycan polysulfuric acid ester.
        Arthritis Rheum. 1989; 32: 759-766
        • Altman RD
        • Dean DD
        • Muniz OE
        • Howell DS
        Therapeutic treatment of canine osteoarthritis with glycosaminoglycan polysulfuric acid ester.
        Arthritis Rheum. 1989; 32: 1300-1307
        • Dean DD
        • Muniz OE
        • Rodriquez I
        • et al.
        Amelioration of lapine osteoarthritis by treatment with glycosaminoglycan-peptide association complex (Rumalon).
        Arthritis Rheum. 1991; 34: 304-313
      3. Altman RD Gottlieb NL Howell DS Hyaluronan. Semin Arthritis Rheum. 22. 1993: 1-51
        • Setnikar I
        • Palumbo R
        • Canali S
        • Zanolo G
        Pharmacokinetics of glucosamine in man.
        Arzneimittelforschung. 1993; 43: 1109-1113
        • Bassleer C
        • Reginster JY
        • Franchimont P
        Effects of glucosamine on differentiated human chondrocytes cultivated in cluster (Abstract).
        Rev Esp Reumatol. 1993; 20 (Mo 96)
        • Raiss R
        Influence of glucosamine sulfate on experimentally impaired articular cartilage: test of ultrastructural changes in chondrocytes using morphometry.
        Fortschr Med. 1985; 103: 658-662
        • Setnikar I
        • Cereda R
        • Pacini MA
        • Revel L
        Antireactive properties of glucosamine sulfate.
        Arzneimittelforschung. 1991; 41: 157-161
        • Setnikar I
        • Pacini MA
        • Revel L
        Antiarthritic effects of glucosamine sulfate studied on animal models.
        Arzneimittelforschung. 1991; 41: 542-545
        • Ghosh P
        • Brooks P
        Chondroprotection: exploring the concept.
        J Rheumatol. 1991; 18: 161-166
        • Adler E
        • Wolf E
        • Taustein I
        A double blind trial with cartilage and bone marrow extract in degenerative gonarthrosis.
        Acta Rheum Scand. 1970; 16: 6-11
        • Dixon AS
        • Kersley GD
        • Mercer R
        • et al.
        A double-blind controlled trial of Rumalon in the treatment of painful osteoarthrosis of the hip.
        Ann Rheum Dis. 1970; 29: 193-194
        • Denko CW
        Treatment of osteoarthritis with Rumalon.
        Arthritis Rheum. 1978; 21: 494-496
        • Siegmeth W
        • Radi I
        Comparison of glycosaminoglycan polysulfate and saline solution in arthrosis of the large joints.
        Z Rheumatol. 1983; 42: 223-228
        • Dixon AStJ
        • Jacoby RK
        • Berry H
        • Hamilton EBD
        Clinical trial of intraarticular injection of sodium hyaluronate in patients with osteoarthritis of the knee.
        Curr Med Res Opin. 1988; 11: 205-213
        • Grecomoro G
        • Martorana V
        • Di Marco C
        Intra-articular treatment with sodium hyaluronate in gonarthrosis. Controlled clinical trial versus placebo.
        Pharmatherapeutica. 1987; 5: 137-141
        • Anderson JJ
        • Firschein HE
        • Meenan FR
        Sensitivity of a healthy status measure to short-term clinical changes in arthritis.
        Arthritis Rheum. 1989; 32: 844-850
        • Tyson VCH
        • Glynne A
        A comparative study of benoxaprofen and ibuprofen in osteoarthritis in general practice.
        J Rheumatol Suppl. 1980; 6: 132-138
        • Levinson DJ
        • Rubinstein HM
        Double-blind comparison of fenoprofen calcium and ibuprofen in osteoarthritis of large joints.
        Curr Ther Res. 1983; 34: 280-284
        • Bradley JD
        • Brandt KD
        • Katz BP
        • Kalasinski LA
        • Ryan SI
        Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee.
        N Engl J Med. 1991; 325: 87-91
        • Lequesne M
        • Samson M
        • Gerard P
        • Mery C
        Algo-functional indices for the follow-up of hip and knee arthrosis.
        Rev Rhum Mal Osteoartic. 1990; 57: 32S-36S
        • Muller-Faßbender H
        • Bach GL
        • Haase W
        • Rovati LC
        • Setnikar I
        Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee.
        Osteoarthritis Cart. 1994; 2: 61-69
        • Rovati LC
        • Setnikar I
        • Förster KK
        • Reichelt A
        • Noack W
        Glucosamine sulfate in gonarthrosis: efficacy in placebo controlled studies (Abstract).
        Rev Esp Reumatol. 1993; 20: 72
        • Giacovelli G
        • Rovati LC
        Clinical efficacy of glucosamine sulfate in osteoarthritis of the spine (Abstract).
        Rev Esp Reumatol. 1993; 20 (Mo 96)
        • Berg PA
        • Dürk H
        • Saal J
        • Hopf G
        Bovine cartilage and marrow extract.
        Lancet. 1989; 1: 1275
        • Greiling H
        Biochemical studies of potentially antiarthrotic drugs.
        Z Rheumatol. 1983; 42: 153-158
      4. (Suppl 1)
        • Serni U
        Profile of glucosamine sulfate as an example of Slow Acting Drug in Osteoarthritis.
        in: Proceedings of the XVIIIth ILAR Congress of Rheumatology. Rev Esp Reumatol. 20. 1993: 222