Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
European Journal of Medical Research
Published in: European Journal of Medical Research 1/2015

Open Access 01-12-2015 | Research

Efficacy and safety of glucosamine, diacerein, and NSAIDs in osteoarthritis knee: a systematic review and network meta-analysis

Authors: Jatupon Kongtharvonskul, Thunyarat Anothaisintawee, Mark McEvoy, John Attia, Patarawan Woratanarat, Ammarin Thakkinstian

Published in: European Journal of Medical Research | Issue 1/2015

Login to get access

Abstract

Background

To conduct a systematic review and network meta-analysis of randomized controlled trials (RCTs) with the aims of comparing relevant clinical outcomes (that is, visual analog scores (VAS), total and sub-Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) scores, Lequesne algofunctional index, joint space width change, and adverse events) between diacerein, glucosamine, and placebo.

Methods

Medline and Scopus databases were searched from inception to 29 August 2014, using PubMed and Scopus search engines and included RCTs or quasi-experimental designs comparing clinical outcomes between treatments. Data were extracted from original studies. A network meta-analysis was performed by applying weight regression for continuous outcomes and a mixed-effect Poisson regression for dichotomous outcomes.

Results

Thirty-one of 505 identified studies were eligible. Compared to placebo, glucosamine showed a significant improvement with unstandardized mean differences (UMD) in total WOMAC, pain WOMAC, function WOMAC, and Lequesne score of −2.49 (95% confidence interval (CI) −4.14, −0.83), −0.75 (95% CI: −1.18, −0.32), −4.78 (95% CI: −5.96, −3.59), and −1.03 (95% CI: −1.34, −0.72), respectively. Diacerein clinically improves visual analog scores, function WOMAC, and stiffness WOMAC with UMD values of −2.23 (95% CI: −2.82, −1.64), −6.64 (95% CI: −10.50, −2.78), and −0.68 (95% CI: −1.20, −0.16) when compared to placebo.

Conclusions

The network meta-analysis suggests that diacerein and glucosamine are equally efficacious for symptom relief in knee OA, but that the former has more side effects.
Appendix
Available only for authorised users
Literature
1.
Blandizzi C, Tuccori M, Colucci R, Fornai M, Antonioli L, Ghisu N, et al. Role of coxibs in the strategies for gastrointestinal protection in patients requiring chronic non-steroidal anti-inflammatory therapy. Pharmacol Res Off J Italian Pharmacol Soc. 2009;59(2):90–100. doi:10.1016/j.phrs.2008.11.004.CrossRef
2.
Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001;286(8):954–9.CrossRefPubMed
3.
Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005;2:CD002946. doi:10.1002/14651858.CD002946.pub2.PubMed
4.
Rintelen B, Neumann K, Leeb BF. A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis. Arch Intern Med. 2006;166(17):1899–906. doi:10.1001/archinte.166.17.1899.CrossRefPubMed
5.
Wandel S, Juni P, Tendal B, Nuesch E, Villiger PM, Welton NJ, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. BMJ. 2010;341:c4675. doi:10.1136/bmj.c4675.CrossRefPubMedCentralPubMed
6.
Bartels EM, Bliddal H, Schondorff PK, Altman RD, Zhang W, Christensen R. Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials. Osteoarthritis Cartilage. 2010;18(3):289–96. doi:10.1016/j.joca.2009.10.006.CrossRefPubMed
7.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100. doi:10.1371/journal.pmed.1000100.CrossRefPubMedCentralPubMed
8.
Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. 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. 1988;15(12):1833–40.PubMed
9.
Lequesne MG. The algofunctional indices for hip and knee osteoarthritis. J Rheumatol. 1997;24(4):779–81.PubMed
10.
11.
Palmer TMPJ, Sutton AJ, Moreno SG. Contour-enhanced funnel plots in meta-analysis. STATA J. 2009;8(2):242–54.
12.
Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol. 2008;61(10):991–6. doi:S0895-4356(07)00435-0.CrossRefPubMed
13.
14.
Song F, Altman DG, Glenny AM, Deeks JJ. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ. 2003;326(7387):472. doi:10.1136/bmj.326.7387.472.CrossRefPubMedCentralPubMed
15.
Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med. 2004;23(20):3105–24. doi:10.1002/sim.1875.CrossRefPubMed
16.
Song F, Harvey I, Lilford R. Adjusted indirect comparison may be less biased than direct comparison for evaluating new pharmaceutical interventions. J Clin Epidemiol. 2008;61(5):455–63. doi:10.1016/j.jclinepi.2007.06.006.CrossRefPubMed
17.
Pilotto A, Franceschi M, Vitale DF, Zaninelli A, Masotti G, Rengo F. Upper gastrointestinal symptoms and therapies in elderly out-patients, users of non-selective NSAIDs or coxibs. Aliment Pharmacol Ther. 2005;22(2):147–55.CrossRefPubMed
18.
Brahmachari B, Chatterjee S, Ghosh A. Efficacy and safety of diacerein in early knee osteoarthritis: a randomized placebo-controlled trial. Clin Rheumatol. 2009;28(10):1193–8. doi:10.1007/s10067-009-1225-9.CrossRefPubMed
19.
Dougados M, Nguyen M, Berdah L, Mazieres B, Vignon E, Lequesne M. Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation Chondromodulating Effect Diacerein OA Hip. Arthritis Rheum. 2001;44(11):2539–47.CrossRefPubMed
20.
Louthrenoo W, Nilganuwong S, Aksaranugraha S, Asavatanabodee P, Saengnipanthkul S. The efficacy, safety and carry-over effect of diacerein in the treatment of painful knee osteoarthritis: a randomised, double-blind. NSAID-Controlled Stuty. Osteoarthritis Cartilage. 2007;15(6):605–14. doi:10.1016/j.joca.2007.02.021.CrossRefPubMed
21.
Nguyen M, Dougados M, Berdah L, Amor B. Diacerein in the treatment of osteoarthritis of the hip. Arthritis Rheum. 1994;37(4):529–36.CrossRefPubMed
22.
Pavelka K, Trc T, Karpas K, Vitek P, Sedlackova M, Vlasakova V, et al. The efficacy and safety of diacerein in the treatment of painful osteoarthritis of the knee: a randomized, multicenter, double-blind, placebo-controlled study with primary end points at two months after the end of a three-month treatment period. Arthritis Rheum. 2007;56(12):4055–64. doi:10.1002/art.23056.CrossRefPubMed
23.
Pelletier JP, Yaron M, Haraoui B, Cohen P, Nahir MA, Choquette D, et al. Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group. Arthritis Rheum. 2000;43(10):2339–48. doi:10.1002/1529-0131(200010)43:10 < 2339::aid-anr23 > 3.0.co;2-p.CrossRefPubMed
24.
Pham T, Le Henanff A, Ravaud P, Dieppe P, Paolozzi L, Dougados M. Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis. Ann Rheum Dis. 2004;63(12):1611–7. doi:10.1136/ard.2003.019703.CrossRefPubMedCentralPubMed
25.
Zheng WJ, Tang FL, Li J, Zhang FC, Li ZG, Su Y, et al. Evaluation of efficacy and safety of diacerein in knee osteoarthritis in Chinese patients. Chin Med Sci J. 2006;21(2):75–80.PubMed
26.
Braham R, Dawson B, Goodman C. The effect of glucosamine supplementation on people experiencing regular knee pain. Br J Sports Med. 2003;37(1):45–9. discussion 9.CrossRefPubMedCentralPubMed
27.
Cibere J, Kopec JA, Thorne A, Singer J, Canvin J, Robinson DB, et al. Randomized, double-blind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis Rheum. 2004;51(5):738–45. doi:10.1002/art.20697.CrossRefPubMed
28.
Clegg DO, Reda DJ, Harris CL, Klein MA, O’Dell JR, Hooper MM, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354(8):795–808. doi:10.1056/NEJMoa052771.CrossRefPubMed
29.
Frestedt JL, Walsh M, Kuskowski MA, Zenk JL. A natural mineral supplement provides relief from knee osteoarthritis symptoms: a randomized controlled pilot trial. Nutr J. 2008;7:9. doi:10.1186/1475-2891-7-9.CrossRefPubMedCentralPubMed
30.
Herrero-Beaumont G, Ivorra JA, Del Carmen TM, Blanco FJ, Benito P, Martin-Mola E, et al. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum. 2007;56(2):555–67. doi:10.1002/art.22371.CrossRefPubMed
31.
Houpt JB, McMillan R, Wein C, Paget-Dellio SD. Effect of glucosamine hydrochloride in the treatment of pain of osteoarthritis of the knee. J Rheumatol. 1999;26(11):2423–30.PubMed
32.
Hughes R, Carr A. A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology (Oxford). 2002;41(3):279–84.CrossRef
33.
Kawasaki T, Kurosawa H, Ikeda H, Kim SG, Osawa A, Takazawa Y, et al. Additive effects of glucosamine or risedronate for the treatment of osteoarthritis of the knee combined with home exercise: a prospective randomized 18-month trial. J Bone Miner Metab. 2008;26(3):279–87. doi:10.1007/s00774-007-0813-5.CrossRefPubMed
34.
Lopes VA. 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 Opin. 1982;8(3):145–9. doi:10.1185/03007998209112375.CrossRef
35.
McAlindon T, Formica M, LaValley M, Lehmer M, Kabbara K. Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an internet-based randomized double-blind controlled trial. Am J Med. 2004;117(9):643–9. doi:10.1016/j.amjmed.2004.06.023.CrossRefPubMed
36.
Muller-Fassbender H, Bach GL, Haase W, Rovati LC, Setnikar I. Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee. Osteoarthritis Cartilage. 1994;2(1):61–9.CrossRefPubMed
37.
Noack W, Fischer M, Forster KK, Rovati LC, Setnikar I. Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage. 1994;2(1):51–9.CrossRefPubMed
38.
Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2002;162(18):2113–23.CrossRefPubMed
39.
Pujalte JM, Llavore EP, Ylescupidez FR. Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis. Curr Med Res Opin. 1980;7(2):110–4. doi:10.1185/03007998009112036.CrossRefPubMed
40.
Qiu GX, Gao SN, Giacovelli G, Rovati L, Setnikar I. Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with knee osteoarthritis. Arzneimittelforschung. 1998;48(5):469–74.PubMed
41.
Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet. 2001;357(9252):251–6. doi:10.1016/s0140-6736(00)03610-2.CrossRefPubMed
42.
Rindone JP, Hiller D, Collacott E, Nordhaugen N, Arriola G. Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med. 2000;172(2):91–4.CrossRefPubMedCentralPubMed
43.
Rozendaal RM, Koes BW, van Osch GJ, Uitterlinden EJ, Garling EH, Willemsen SP, et al. Effect of glucosamine sulfate on hip osteoarthritis: a randomized trial. Ann Intern Med. 2008;148(4):268–77.CrossRefPubMed
44.
Sawitzke AD, Shi H, Finco MF, Dunlop DD, Bingham 3rd CO, Harris CL, et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum. 2008;58(10):3183–91. doi:10.1002/art.23973.CrossRefPubMedCentralPubMed
45.
Durmus D, Alayli G, Bayrak IK, Canturk F. Assessment of the effect of glucosamine sulfate and exercise on knee cartilage using magnetic resonance imaging in patients with knee osteoarthritis: a randomized controlled clinical trial. J Back Musculoskeletal Rehabil. 2012;25(4):275–84. doi:10.3233/bmr-2012-0336.
46.
Kwoh CK, Roemer FW, Hannon MJ, Moore CE, Jakicic JM, Guermazi A, et al. Effect of oral glucosamine on joint structure in individuals with chronic knee pain: a randomized, placebo-controlled clinical trial. Arthritis Rheumatol (Hoboken NJ). 2014;66(4):930–9. doi:10.1002/art.38314.CrossRef
47.
Madhu K, Chanda K, Saji MJ. Safety and efficacy of Curcuma longa extract in the treatment of painful knee osteoarthritis: a randomized placebo-controlled trial. Inflammopharmacology. 2013;21(2):129–36. doi:10.1007/s10787-012-0163-3.CrossRefPubMed
48.
Chopra A, Saluja M, Tillu G, Sarmukkaddam S, Venugopalan A, Narsimulu G, et al. Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial. Rheumatology (Oxford). 2013;52(8):1408–17. doi:10.1093/rheumatology/kes414.CrossRef
49.
Wu D, Huang Y, Gu Y, Fan W. Efficacies of different preparations of glucosamine for the treatment of osteoarthritis: a meta-analysis of randomised, double-blind, placebo-controlled trials. Int J Clin Pract. 2013;67(6):585–94. doi:10.1111/ijcp.12115.CrossRefPubMed
50.
Michel BA, Stucki G, Frey D, De Vathaire F, Vignon E, Bruehlmann P, et al. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial. Arthritis Rheum. 2005;52(3):779–86. doi:10.1002/art.20867.CrossRefPubMed
51.
Mazieres B, Hucher M, Zaim M, Garnero P. Effect of chondroitin sulphate in symptomatic knee osteoarthritis: a multicentre, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2007;66(5):639–45. doi:10.1136/ard.2006.059899.CrossRefPubMedCentralPubMed
52.
Kahan A, Uebelhart D, De Vathaire F, Delmas PD, Reginster JY. Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: the study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2009;60(2):524–33. doi:10.1002/art.24255.CrossRefPubMed
53.
Tashiro T, Seino S, Sato T, Matsuoka R, Masuda Y, Fukui N. Oral administration of polymer hyaluronic acid alleviates symptoms of knee osteoarthritis: a double-blind, placebo-controlled study over a 12-month period. TheScientificWorldJOURNAL. 2012;2012:167928. doi:10.1100/2012/167928.CrossRefPubMedCentralPubMed
54.
Appelboom T, Schuermans J, Verbruggen G, Henrotin Y, Reginster JY. Symptoms modifying effect of avocado/soybean unsaponifiables (ASU) in knee osteoarthritis. A double blind, prospective, placebo-controlled study. Scand J Rheumatol. 2001;30(4):242–7.CrossRefPubMed
55.
Pujol JP, Chadjichristos C, Legendre F, Bauge C, Beauchef G, Andriamanalijaona R, et al. Interleukin-1 and transforming growth factor-beta 1 as crucial factors in osteoarthritic cartilage metabolism. Connect Tissue Res. 2008;49(3):293–7. doi:10.1080/03008200802148355.CrossRefPubMed
Metadata
Title
Efficacy and safety of glucosamine, diacerein, and NSAIDs in osteoarthritis knee: a systematic review and network meta-analysis
Authors
Jatupon Kongtharvonskul
Thunyarat Anothaisintawee
Mark McEvoy
John Attia
Patarawan Woratanarat
Ammarin Thakkinstian
Publication date
01-12-2015
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2015
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-015-0115-7

Other articles of this Issue 1/2015

European Journal of Medical Research 1/2015 Go to the issue

Research

An analysis of the association between a polymorphism of KCNJ11 and diabetic retinopathy in a Chinese Han population

Research

MiR-133a is downregulated in non-small cell lung cancer: a study of clinical significance

Research

Rapamycin impairs endothelial cell function in human internal thoracic arteries

Research

Association between plasma ADAMTS-7 levels and ventricular remodeling in patients with acute myocardial infarction

Research

Sertoli cell-mediated differentiation of male germ cell-like cells from human umbilical cord Wharton’s jelly-derived mesenchymal stem cells in an in vitro co-culture system

Research

Better short-term efficacy of treating severe flail chest with internal fixation surgery compared with conservative treatments