Crystalline glucosamine sulfate in the management of knee osteoarthritis: Efficacy, safety, and pharmacokinetic properties

Therapeutic Advances in Musculoskeletal Disease

Volumn 4, Issue 3, 2012, Pages 167-180

  Rovati, Lucio C ^a   Girolami, Federica ^a   Persiani, Stefano ^a  

^a Rotta Research Laboratorium   (Italy)

Author keywords

efficacy; glucosamine; glucosamine hydrochloride; glucosamine sulfate; knee osteoarthritis; pharmacokinetics; safety

Indexed keywords

GLUCOSAMINE; GLUCOSAMINE SULFATE; GLUSARTEL; NONSTEROID ANTIINFLAMMATORY AGENT; OSAFLEXAN; PHENYLBUTAZONE; PLACEBO; UNCLASSIFIED DRUG; VIARTRIL S; XICIL;

ABDOMINAL PAIN; ANALGESIA; AREA UNDER THE CURVE; ARTICLE; CONSTIPATION; COST EFFECTIVENESS ANALYSIS; DIARRHEA; DIASTOLIC BLOOD PRESSURE; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG COST; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; DYSPEPSIA; ERYTHEMA; FATIGUE; FLATULENCE; GASTROINTESTINAL SYMPTOM; GLUCOSE BLOOD LEVEL; HUMAN; KNEE OSTEOARTHRITIS; MAXIMUM PLASMA CONCENTRATION; META ANALYSIS (TOPIC); NAUSEA; NONHUMAN; PAIN ASSESSMENT; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; SIDE EFFECT; SINGLE DRUG DOSE; SOMNOLENCE; SYSTOLIC BLOOD PRESSURE;

EID: 84868647956     PISSN: 1759720X     EISSN: 17597218     Source Type: Journal    
DOI: 10.1177/1759720X12437753     Document Type: Article

References (74)

1. Ali A.A. Lewis S.M. Badgley H.L. Allaben W.T. Leakey J.E. (2011) Oral glucosamine increases expression of transforming growth factor 1 (TGF1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: implications for human efficacy and toxicity. Arch Biochem Biophys 510: 11–18.
2. Altman R.D. (2009) Glucosamine therapy for knee osteoarthritis: pharmacokinetic considerations. Expert Rev Clin Pharmacol 2: 359–371.
3. Altman R.D. Cheung H. (2001) Glucosamine sulfate on cartilage: lapine study. Arthritis Rheum 44(Suppl 9): 1535.
4. Baron A.D. Zhu J.S. Zhu J.H. Weldon H. Maianu L. Garvey W.T. et al. (1995) Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity. J Clin Invest 96: 2792–2801.
5. Bassleer C. Rovati L.C. Franchimont P. (1998) Glucosamine sulfate stimulates proteoglycan production in human chondrocytes in vitro. Osteoarthritis Cartilage 6: 427–434.
6. Biggee B.A. Blinn C.M. McAlindon T.E. Nuite M. Silbert J.E. (2006) Low levels of human serum glucosamine after ingestion of glucosamine sulfate relative to capability for peripheral effectiveness. Ann Rheum Dis 65: 222–226.
7. Bjordal J.M. Ljunggren A.E. Klovning A. Slørdal L. (2004) Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritis knee pain: meta-analysis of randomised placebo controlled trials. BMJ 329: 1317–1322.
8. Black C. Clar C. Henerson R. MacEachen C. McNamee P. Quayyum Z. et al. (2009) The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation. Health Technol Assess 13 (52).
9. Block J.A. Oegema T.R. Sandy J.D. Plaas A. (2010) The effects of oral glucosamine on joint health: is a change in research approach needed? Osteoarthritis Cartilage 18: 5–11.
10. Bruyere O. Pavelka K. Rovati L.C. Gatterová J. Giacovelli G. Olejarová M. et al. (2008) Total joint replacement after glucosamine sulfate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials. Osteoarthritis Cartilage 16: 254–260.
11. Chiusaroli R. Piepoli T. Zanelli T. Ballanti P. Lanza M. Rovati L.C. et al. (2011) Experimental pharmacology of glucosamine sulfate. Int J Rheumatol 2011: 939265 [Epub].
12. Clegg D.O. Reda D.J. Harris C.L. Klein M.A. O'Dell J.R. Hooper M.M. et al. (2006) Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 358: 795–808.
13. Cordoba F. Nimni M.E. (2003) Chondroitin sulfate and other sulfate containing chondroprotective agents may exhibit their effects by overcoming a deficiency of sulfur amino acids. Osteoarthritis Cartilage 11: 228–230.
14. de Wan M. Volpi G. ; inventors. (1997) A method of preparing mixed glucosamine salts. US patent 5,847,107. 13 August 1997.
15. Dodge G.R. Jimenez S.A. (2003) Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes. Osteoarthritis Cartilage 11: 424–432.
16. Dostrovsky N.R. Towheed T.E. Hudson R.W. Anastassiades T.P. (2011) The effect of glucosamine on glucose metabolism in humans: a systematic review of the literature. Osteoarthritis Cartilage 19: 375–380.
17. Felson D.T. Zhang Y. (1998) An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis Rheum 41: 1343–1355.
18. Giacovelli G. Rovati L.C. (2010) One more meta-analysis confirms the efficacy of prescription glucosamine sulphate in knee osteoarthritis. BMJ 341:c6338 [full text accessible at http://www.bmj.com/content/341/bmj.c4675.full/reply#bmj_el_242904].
19. Gouze J.N. Bianchi A. Becuwe P. Dauça M. Netter P. Magdalou J. et al. (2002) Glucosamine modulates IL-1-induced activation of rat chondrocytes at a receptor level, and by inhibiting the NF-kappaB pathway. FEBS Lett 510: 166–170.
20. Gouze J.N. Bordji K. Gulberti S. Terlain B. Netter P. Magdalou J. et al. (2001) Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes. Arthritis Rheum 44: 351–360.
21. Groves T. (2011) Report from BMJ post-publication review meeting [accessible at http://www.bmj.com/content/341/bmj.c4675.full/reply#bmj_el_247719].
22. Guccione A.A. Felson D.T. Anderson J.J. Anthony J.M. Zhang Y. Wilson P.W. et al. (1994) The effects of specific medical conditions on the functional limitations of elders in the Framingham Study. Am J Public Health 84: 351–358.
23. Hamerman D. (1989) The biology of osteoarthritis. N Engl J Med 320: 1322–1330.
24. Hedges L.V. Olkin I. (1985) Statistical Methods for Meta-analysis. Orlando, FL: Academic Press.
25. Herrero-Beaumont G. Ivorra J.A. DelCarmen Trabado M.C. Blanco F.J. Benito P. Martín-Mola E. et al. (2007) Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomised, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum 56: 555–567.
26. Hoffer L.J. Kaplan L.N. Hamadeh M.J. Grigoriu A.C. Baron M. (2001) Sulfate could mediate the therapeutic effect of glucosamine sulfate. Metabolism 50: 767–770.
27. Imagawa K. de Andrés M.C. Hashimoto K. Pitt D. Itoi E. Goldring M.B. et al. (2011) The epigenetic effect of glucosamine and a nuclear factor-kappa B (NF-kB) inhibitor on primary human chondrocytes – implications for osteoarthritis. Biochem Biophys Res Commun 405: 362–367.
28. Jackson C.G. Plaas A.H. Sandy J.D. Hua C. Kim-Rolands S. Barnhill J.G. et al. (2010) The human pharmacokinetics of oral ingestion of glucosamine and chondroitin sulfate taken separately or in combination. Osteoarthritis Cartilage 18: 297–302.
29. Jordan K.M. Arden N.K. Doherty M. Bannwarth B. Bijlsma J.W. Dieppe P. et al. (2003) EULAR recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 62: 1145–1155.
30. Largo R. Alvarez-Soria M.A. Dìez-Ortego I. Calvo E. Sánchez-Pernaute O. Egido J. et al. (2003) Glucosamine inhibits IL-1β-induced NFKB activation in human osteoarthritic chondrocytes. Osteoarthritis Cartilage 11: 290–298.
31. Letari O. Colombo S. Zanelli T. Piepoli T. Makovec F. Rovati L.C. (2003) The mechanism of action of glucosamine sulfate in osteoarthritis: IL-1β-mediated reactive oxygen species and modulation of NF-κB pathway. Arthritis Rheum 48(Suppl 9): 664.
32. Mason R.M. Chambers M.G. Flannelly J. Gaffen J.D. Dudhia J. Bayliss M.T. (2001) The STR/ort mouse and its use as a model of osteoarthritis. Osteoarthritis Cartilage 9: 85–91.
33. McAlindon T. Formica M. LaValley M. Lehmer M. Kabbara K. (2004) Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med 117: 643–649.
34. Meulyzer M. Vachon P. Beaudry F. Vinardell T. Richard H. Beauchamp G. et al. (2008) Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride. Osteoarthritis Cartilage 16: 973–979.
35. Monauni T. Zenti M.G. Cretti A. Daniels M.C. Targher G. Caruso B. et al. (2000) Effects of glucosamine infusion on insulin secretion and insulin action in humans. Diabetes 49: 926–935.
36. Mroz P.J. Silbert J.E. (2004) Use of 3H-glucosamine and 35S-sulfate with cultured human chondrocytes to determine the effect of glucosamine concentration on formation of chondroitin sulfate. Arthritis Rheum 50: 3574–3579.
37. Muniyappa R. Karne R.J. Hall G. Crandon S.K. Bronstein J.A. Ver M.R. et al. (2006) Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects. Diabetes 55: 3142–3150.
38. National Collaborating Centre for Chronic Conditions, Royal College of Physicians. (2008) Osteoarthritis: National Clinical Guideline for Care and Management in Adults. NICE Clinical Guideline 59. London: National Institute for Health and Clinical Excellence.
39. Noack W. Fischer M. Forster K.K. Rovati L.C. Setnikar I. (1994) Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage 2: 51–59.
40. Noyszewski E.A. Wroblewski K. Dodge G.R. Kudchodkar S. Beers J. Sarma A.V. et al. (2001) Preferential incorporation of glucosamine into the galactosamine moieties of chondroitin sulfate in articular cartilage explants. Arthritis Rheum 44: 1089–1095.
41. Oliveira S.A. Felson D.T. Reed J.I. Cirillo P.A. Walker A.M. (1995) Incidence of symptomatic hand, hip and knee osteoarthritis among patients in a health maintenance organisation. Arthritis Rheum 38: 1134–1141.
42. Palma dos Reis R. Giacovelli G. Girolami F. André R. Bonazzi A. Rovati L.C. (2011) Crystalline glucosamine sulfate in the treatment of osteoarthritis: evidence of long-term cardiovascular safety from clinical trials. Open Rheumatol J 5: 69–77.
43. Pavelka K. Gatterova J. Olejarova M. Machacek S. Giacovelli G. Rovati L.C. et al. (2002) Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 162: 2113–2123.
44. Pelletier J.P. Hochberg M.C. du Souich P. Kahan A. Michel B.A. (2010) Symptomatic and disease modifying effects of chondroitin sulphate and glucosamine BMJ 341: c 6328 [full text accessible at http://www.bmj.com/content/341/bmj.c4675.full/reply#bmj_el_242776].
45. Pendleton A. Arden N. Dougados M. Doherty M. Bannwarth B. Bijlsma J.W. et al. (2000) EULAR recommendations for the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 59: 936–944.
46. Persiani S. Canciani L. Ricci V. Larger P. Paganini D. Rovati L.C. (2006) Glucosamine does not inhibit or induce human cytochromes P450. Drug Metab Rev 38: 255.
47. Persiani S. Larger P. Canciani L. Matthews A. Hall M. Rovati L.C. (2008) Evaluation of crystalline glucosamine sulfate plasma to blood partitioning and protein binding in human and mouse plasma and binding in human synovial fluid. Drug Metab Rev 40: 255.
48. Persiani S. Locatelli M. Fiorentino S. Rovati L.C. Roda A. (2005 a) Absolute bioavailability of glucosamine after administration of crystalline glucosamine sulfate in rats. Osteoarthritis Cartilage 13 (Suppl. A): P161.
49. Persiani S. Roda E. Rovati L.C. Locatelli M. Giacovelli G. Roda A. (2005 b) Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man. Osteoarthritis Cartilage 13: 1041–1049.
50. Persiani S. Rotini R. Trisolino G. Rovati L.C. Locatelli M. Paganini D. et al. (2007) Synovial and plasma glucosamine concentrations in osteoarthritic patients following oral crystalline glucosamine sulfate at therapeutic dose. Osteoarthritis Cartilage 15: 764–772.
51. Piperno M. Reboul P. Helio L.e. Graverand M.P. Peschard M.J. Annefeld M. Richard M. et al. (2000) Glucosamine sulfate modulates dysregulated activities of human osteoarthritic chondrocytes in vitro. Osteoarthritis Cartilage 8: 207–212.
52. Pocock S.J. (2007) Safety of drug-eluting stents: demystifying network meta-analysis. Lancet 370: 2099–2100.
53. Pouwels M.J. Jacobs J.R. Span P.N. Lutterman J.A. Smits P. Tack C.J. (2001) Short-term glucosamine infusion does not affect insulin sensitivity in humans. J Clin Endocrinol Metab 86: 2099–2103.
54. Reginster J.Y. (2007) Editorial. The efficacy of glucosamine sulfate in osteoarthritis: financial and nonfinancial conflict of interest. Arthritis Rheum 56: 2105–2110.
55. Reginster J.Y. Altman R.D. Hochberg M.C. (2010) Prescription glucosamine sulphate is effective in knee osteoarthritis. BMJ 341: c 6335 [full text available at http://www.bmj.com/content/341/bmj.c4675.full/reply#bmj_el_242366].
56. Reginster J.Y. Deroisy R. Rovati L.C. Lee R.L. Lejeune E. Bruyere O. et al. (2001) Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomized, placebo-controlled clinical trial. Lancet 357: 251–256.
57. Roda A. Sabatini L. Barbieri A. Guardigli M. Locatelli M. Violante F.S. et al. (2006) Development and validation of a sensitive HPLC-ESI-MS/MS method for the direct determination of glucosamine in human plasma. J Chromatogr B 844: 119–126.
58. Rozendaal R.M. Koes B.W. van Osch G.J. Uitterlinden E.J. Garling E.H. Willemsen S.P. et al. (2008) Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial. Ann Intern Med 148: 268–277.
59. Russell A.S. Aghazadeh-Habashi A. Jamali F. (2002) Active ingredient consistency of commercially available glucosamine sulfate products. J Rheumatol 29: 2407–2409.
60. Sandy J.D. Gamett 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.
61. Sawitzke A.D. Shi H. Finco M.F. Dunlop D.D. Bingham C.O. 3rd Harris C.L. et al. (2008) The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis. Arthritis Rheum 58: 3183–3191.
62. Scholtissen S. Bruyere O. Neuprez A. Severens J.L. Herrero-Beaumont G. Rovati L.C. et al. (2010) Glucosamine sulfate in the treatment of knee osteoarthritis: cost-effectiveness comparison with paracetamol. Int J Clin Pract 64: 756–762.
63. Setnikar I. Rovati L.C. (2001) Absorption, distribution, metabolism and excretion of glucosamine sulfate: a review. Arzneimittelforschung 51: 699–725.
64. Shankar R.R. Zhu J.S. Baron A.D. (1998) Glucosamine infusion in rats mimics the beta-cell dysfunction of non-insulin-dependent diabetes mellitus. Metabolism 47: 573–577.
65. Shikhman A.R. Kuhn K. Alaaeddine N. Lotz M. (2001) N-acetylglucosamine prevents IL-1 beta-mediated activation of human chondrocytes. J Immunol 166: 5155–5160.
66. Simon R.R. Marks V. Leeds A.R. Anderson J.W. (2011) A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals. Diabetes Metab Res Rev 27: 14–27.
67. Towheed T. Maxwell L. Anastassiades T.P. Shea B. Houpt J. Robinson V. et al. (2009) Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2: CD002946.pub2. DOI: 10.1002/14651858.CD00294610.1002/14651858.CD002946.
68. Uitterlinden E.J. Jahr H. Koevoet J.L.M. Jenniskens Y.M. Bierma-Zeinstra S.M. Degroot J. et al. (2006) Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants. Osteoarthritis Cartilage 14: 250–257.
69. Varghese S. Theprungsirikul P. Sahani S. Hwang N. Yarema K.J. Elisseeff J.H. (2007) Glucosamine modulates chondrocyte proliferation, matrix synthesis, and gene expression. Osteoarthritis Cartilage 15: 59–68.
70. Wandel S. Jüni P. Tendal B. Nuesch E. Villiger P.M. Welton N.J. et al. (2010) Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ 341: c4675.
71. Wen Z.H. Tang C.C. Chang Y.C. Huang S.Y. Hsieh S.P. Lee C.H. (2010) Glucosamine sulfate reduces experimental osteoarthritis and nociception in rats: association with changes of mitogen-activated protein kinase in chondrocytes. Osteoarthritis Cartilage 18: 1192–1202.
72. Zhang W. Moskowitz R.W. Nuki G. Abramson S. Altman R.D. Arden N. et al. (2007) OARSI recommendations for the management of hip and knee osteoarthritis, Part I: Critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage 15: 981–1000.
73. Zhang W. Moskowitz R.W. Nuki G. Abramson S. Altman R.D. Arden N. et al. (2008) OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 16: 137–162.
74. Zhang W. Nuki G. Moskowitz R.W. Abramson S. Altman R.D. Arden N.K. et al. (2010) OARSI recommendations for the management of hip and knee osteoarthritis, Part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 18: 476–499.