Effects of adding glucosamine or glucosamine combined with chondroitin to exercise on pain and physical function in adults with knee osteoarthritis: a systematic review and meta-analysis

Submitted: 20 October 2023
Accepted: 5 November 2023
Published: 23 November 2023
Abstract Views: 1715
PDF: 924
HTML: 7
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

It is well known that different types of exercise significantly improve physical function and relieve pain in knee osteoarthritis (KOA) patients. The aim of this study was to investigate the added effects of glucosamine or glucosamine and chondroitin supplementation in combination with an exercise program in the management of KOA. The randomized controlled trials on adding glucosamine (G) or G combined with chondroitin (C) to an exercise program in the treatment of KOA were searched in the PubMed, Cochrane Central Register of Controlled Trials, PEDro, and Web of Science online databases. The Pedro scale tool was used to assess quality of literature. A meta-analysis was performed using the Review Manager 5.4 software. In total, 6 studies (including 297 participants) were included for the final meta-analysis. According to the PEDro scale, the average quality of the studies was rated as good (mean = 8.2 (2)). The results showed that the effect of G, or G and C, in combination with exercise is not significant, as indicated by the assessed knee pain (WOMAC pain: SMD -0.18, 95% CI -0.47 to 0.11, p = 0.23; and VAS pain: SMD -0.34, 95% CI -0.85 to 0.17, p = 0.20) and physical function (SMD -0.13, 95% CI -0.95 to 0.69, p = 0.76). Adding glucosamine alone or a combination of glucosamine and chondroitin to exercise, has no effect on knee pain and physical function compared with exercise alone in KOA patients.

Keywords: treatment, dietary supplement, physical activity, older adults

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Annals of the Rheumatic Diseases. BMJ Publishing Group Ltd; 2014 Jul 1;73(7):1323–30. Epub 2014 Feb 19. PMID: 24553908. DOI: https://doi.org/10.1136/annrheumdis-2013-204763
Abbassy AA, Trebinjac S, Kotb N. The use of cellular matrix in symptomatic knee osteoarthritis. Bosn J Basic Med Sci. 2020 May;20(2):271–4. PMCID: PMC7202193. DOI: https://doi.org/10.17305/bjbms.2019.4205
Ashkavand Z, Malekinejad H, Vishwanath BS. The pathophysiology of osteoarthritis. Journal of Pharmacy Research. 2013 Jan 1;7(1):132–8. DOI: https://doi.org/10.1016/j.jopr.2013.01.008
Saito T, Tanaka S. Molecular mechanisms underlying osteoarthritis development: notch and NF-κB. Arthritis Res Ther. 2017 May 15;19(1):94. Epub 2017 May 15. PMID: 28506315; PMCID: PMC5433029. DOI: https://doi.org/10.1186/s13075-017-1296-y
Fernández-Martín S, González-Cantalapiedra A, Muñoz F, García-González M, Permuy M, López-Peña M. Glucosamine and chondroitin sulfate: is there any scientific evidence for their effectiveness as disease-modifying drugs in knee osteoarthritis preclinical studies?-a systematic review from 2000 to 2021. Animals (Basel). 2021 May 29;11(6):1608. PMID: 34072407; PMCID: PMC8228516. DOI: https://doi.org/10.3390/ani11061608
Hanypsiak BT, Shaffer BS. Nonoperative treatment of unicompartmental arthritis of the knee. Orthop Clin North Am. 2005 Oct;36(4):401–11. Epub: 2005 Sep 13. PMID: 16164945. DOI: https://doi.org/10.1016/j.ocl.2005.05.005
McAlindon TE, Biggee BA. Nutritional factors and osteoarthritis: recent developments. Curr Opin Rheumatol. 2005 Sep;17(5):647–52. Epub 2014 Jan 24. PMID: 16093847.
Meng Z, Liu J, Zhou N. Efficacy and safety of the combination of glucosamine and chondroitin for knee osteoarthritis: a systematic review and meta-analysis. Arch Orthop Trauma Surg. 2023 Jan 1;143(1):409–21. Epub 2022 Jan 13. DOI: https://doi.org/10.1007/s00402-021-04326-9
Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018 Feb;52(3):167–75. Epub 2017 Oct 10. PMID: 29018060. DOI: https://doi.org/10.1136/bjsports-2016-097333
Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ. Chondroitin for osteoarthritis. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2015;(1). CD005614.pub2. Epub 2015 Jan 28. PMID: 25629804.
Bruyère O, Altman RD, Reginster JY. Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: evidence from real-life setting trials and surveys. Seminars in Arthritis and Rheumatism. 2016 Feb 1;45(4, Supplement):S12–7. Epub 2015 Dec 2. DOI: https://doi.org/10.1016/j.semarthrit.2015.11.011
Goh SL, Persson MSM, Stocks J, Hou Y, Lin J, Hall MC, Doherty M, Zhang W. Efficacy and potential determinants of exercise therapy in knee and hip osteoarthritis: a systematic review and meta-analysis. Ann Phys Rehabil Med. 2019 Sep;62(5):356–65. Epub 2019 May 21. PMID: 31121333; PMCID: PMC6880792. DOI: https://doi.org/10.1016/j.rehab.2019.04.006
Kus G, Yeldan I. Strengthening the quadriceps femoris muscle versus other knee training programs for the treatment of knee osteoarthritis. Rheumatol Int. 2019 Feb;39(2):203–18. Epub 2018 Nov 15. PMID: 30430202. DOI: https://doi.org/10.1007/s00296-018-4199-6
Zeng CY, Zhang ZR, Tang ZM, Hua FZ. Benefits and mechanisms of exercise training for knee osteoarthritis. Front Physiol. 2021;12:794062. Epub 2021 Dec 16. PMID: 34975542. DOI: https://doi.org/10.3389/fphys.2021.794062
Mat S, Tan MP, Kamaruzzaman SB, Ng CT. Physical therapies for improving balance and reducing falls risk in osteoarthritis of the knee: a systematic review. Age Ageing. 2015 Jan;44(1):16–24. Epub 2014 Aug 22. PMID: 25149678. DOI: https://doi.org/10.1093/ageing/afu112
You Y, Liu J, Tang M, Wang D, Ma X. Effects of tai chi exercise on improving walking function and posture control in elderly patients with knee osteoarthritis: a systematic review and meta-analysis. Medicine (Baltimore). 2021 Apr 23;100(16):e25655. Epub 2021 Apr 23. PMID: 33879749; PMCID: PMC8078456. DOI: https://doi.org/10.1097/MD.0000000000025655
Wang Z, Wang R, Yao H, Yang J, Chen Y, Zhu Y, Lu C. Clinical efficacy and safety of chondroitin combined with glucosamine in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Comput Math Methods Med. 2022;2022:5285244. Epub 2022 Jul 25. PMID: 35924114; PMCID: PMC9343191. DOI: https://doi.org/10.1155/2022/5285244
Methley AM, Campbell S, Chew-Graham C, McNally R, Cheraghi-Sohi S. PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res. 2014 Nov 21;14:579. PMID: 25413154; PMCID: PMC4310146. DOI: https://doi.org/10.1186/s12913-014-0579-0
Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther. 2003 Aug;83(8):713–21. PMID: 12882612. DOI: https://doi.org/10.1093/ptj/83.8.713
Luo D, Wan X, Liu J, Tong T. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018 Jun;27(6):1785–805. Epub 2016 Sep 27. PMID: 27683581. DOI: https://doi.org/10.1177/0962280216669183
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014 Dec 19;14:135. PMID: 25524443; PMCID: PMC4383202. DOI: https://doi.org/10.1186/1471-2288-14-135
Higgins J, Thomas J. Cochrane handbook for systematic reviews of interventions. Available online: https://training.cochrane.org/handbook/current (accessed on 21 March 2023).
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 Musculoskelet Rehabil. Netherlands; 2012;25(4):275–84. PMID: 23220811. DOI: https://doi.org/10.3233/BMR-2012-0336
Kawasaki T, Kurosawa H, Ikeda H, Kim SG, Osawa A, Takazawa Y, Kubota M, Ishijima M. 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. Japan; 2008;26(3):279–87. PMID: 18470670. DOI: https://doi.org/10.1007/s00774-007-0813-5
Messier SP, Mihalko S, Loeser RF, Legault C, Jolla J, Pfruender J, Prosser B, Adrian A, Williamson JD. Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study. Osteoarthritis Cartilage. England; 2007 Nov;15(11):1256–66. Epub 2007 Jun 11. PMID: 17561418. DOI: https://doi.org/10.1016/j.joca.2007.04.016
Osama M, Babur MN, Siddiqi FA, Tassadaq N, Arshad Tareen MA. Effects of glucosamine and chondroitin sulfate supplementation in addition to resistance exercise training and manual therapy in patients with knee osteoarthritis: A randomized controlled trial. J Pak Med Assoc. 2022 Jul;72(7):1272–77. PMID: 36156542.
Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients. Arch Phys Med Rehabil. United States; 2011 Aug;92(8):1185–93. PMID: 21807137. DOI: https://doi.org/10.1016/j.apmr.2011.03.009
Sterzi S, Giordani L, Morrone M, Lena E, Magrone G, Scarpini C, Milighetti S, Pellicciari L, Bravi M, Panni I, Ljoka C, Bressi F, Foti C. The efficacy and safety of a combination of glucosamine hydrochloride, chondroitin sulfate and bio-curcumin with exercise in the treatment of knee osteoarthritis: a randomized, double-blind, placebo-controlled study. Eur J Phys Rehabil Med. Italy; 2016 Jun;52(3):321–30. PMID: 26937646.
Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria committee of the American rheumatism association. Arthritis Rheum. 1986 Aug;29(8):1039–49. PMID: 3741515. DOI: https://doi.org/10.1002/art.1780290816
Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957 Dec;16(4):494–502. Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1006995/ (accessed on 21 March 2023). PMID: 13498604; PMCID: PMC1006995. DOI: https://doi.org/10.1136/ard.16.4.494
McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, Hawker GA, Henrotin Y, Hunter DJ, Kawaguchi H, Kwoh K, Lohmander S, Rannou F, Roos EM, Underwood M. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis and Cartilage. 2014 Mar 1;22(3):363–88. Epub 2014 Jan 14. DOI: https://doi.org/10.1016/j.joca.2014.01.003
Xu Z, Wang Y, Zhang Y, Lu Y, Wen Y. Efficacy and safety of aquatic exercise in knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Clin Rehabil. 2023 Mar;37(3):330–47. Epub 2022 Nov 1. DOI: https://doi.org/10.1177/02692155221134240
Al-Mhanna SB, Mohamed M, Mohd Noor N, Aldhahi MI, Afolabi HA, Mutalub YB, Irekeola AA, Bello KE, Wan Ghazali WS. Effects of circuit training on patients with knee osteoarthritis: a systematic review and meta-analysis. Healthcare (Basel). 2022 Oct 15;10(10):2041. PMID: 36292488; PMCID: PMC9601599. DOI: https://doi.org/10.3390/healthcare10102041
Guo X, Zhao P, Zhou X, Wang J, Wang R. A recommended exercise program appropriate for patients with knee osteoarthritis: A systematic review and meta-analysis. Front Physiol. 2022;13:934511. Epub 2022 Oct 3. PMID: 36262252; PMCID: PMC9574341. DOI: https://doi.org/10.3389/fphys.2022.934511
Hua J, Sun L, Teng Y. Effects of high-intensity strength training in adults with knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Am J Phys Med Rehabil. 2023 Apr 1;102(4):292–99. Epub 2022 Sep 12. DOI: https://doi.org/10.1097/PHM.0000000000002088
Jurado-Castro JM, Muñoz-López M, Ledesma AST, Ranchal-Sanchez A. Effectiveness of exercise in patients with overweight or obesity suffering from knee osteoarthritis: a systematic review and meta-analysis. Int J Environ Res Public Health. 2022 Aug 24;19(17):10510. PMID: 36078226; PMCID: PMC9518463. DOI: https://doi.org/10.3390/ijerph191710510
Roman-Blas J, Castañeda S, Sánchez-Pernaute O, Largo R, Herrero-Beaumont G. Combined treatment with chondroitin sulfate and glucosamine sulfate shows no superiority over placebo for reduction of joint pain and functional impairment in patients with knee osteoarthritis: a six-month multicenter, randomized, double-blind, placebo-controlled clinical trial. Arthritis Rheumatol; 2017 Jan;69(1). PMID: 27477804. DOI: https://doi.org/10.1002/art.39819
Fransen M, Agaliotis M, Nairn L, Votrubec M, Bridgett L, Su S, Jan S, March L, Edmonds J, Norton R, Woodward M, Day R, LEGS study collaborative group. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2015 May;74(5):851–8. Epub 2014 Jan 6. PMID: 24395557. DOI: https://doi.org/10.1136/annrheumdis-2013-203954
Zeng C, Wei J, Li H, Wang Y lun, Xie D xing, Yang T, Gao S guang, Li Y sheng, Luo W, Lei G hua. Effectiveness and safety of Glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee. Sci Rep. 2015 Nov 18;5:16827. PMID: 26576862; PMCID: PMC4649492. DOI: https://doi.org/10.1038/srep16827
Hungerford DS, Jones LC. Glucosamine and chondroitin sulfate are effective in the management of osteoarthritis. J Arthroplasty. 2003 Apr;18(3 Suppl 1):5–9. PMID: 12730919. DOI: https://doi.org/10.1054/arth.2003.50067
Bruyère O, Honvo G, Veronese N, Arden NK, Branco J, Curtis EM, Al-Daghri NM, Herrero-Beaumont G, Martel-Pelletier J, Pelletier JP, Rannou F, Rizzoli R, Roth R, Uebelhart D, Cooper C, Reginster JY. An updated algorithm recommendation for the management of knee osteoarthritis from the European society for clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO). Semin Arthritis Rheum. 2019 Dec;49(3):337–50. Epub 2019 Apr 30. PMID: 31126594. DOI: https://doi.org/10.1016/j.semarthrit.2019.04.008
Altman RD. Glucosamine therapy for knee osteoarthritis: pharmacokinetic considerations. Expert Rev Clin Pharmacol. 2009 Jul;2(4):359–71. PMID: 22112180. DOI: https://doi.org/10.1586/ecp.09.17
Runhaar J, Rozendaal RM, van Middelkoop M, Bijlsma HJW, Doherty M, Dziedzic KS, Lohmander LS, McAlindon T, Zhang W, Bierma Zeinstra S. Subgroup analyses of the effectiveness of oral glucosamine for knee and hip osteoarthritis: a systematic review and individual patient data meta-analysis from the OA trial bank. Ann Rheum Dis. 2017 Nov;76(11):1862–9. Epub 2017 Jul 28. PMID: 28754801. DOI: https://doi.org/10.1136/annrheumdis-2017-211149
Hochberg MC, Martel-Pelletier J, Monfort J, Möller I, Castillo JR, Arden N, Berenbaum F, Blanco FJ, Conaghan PG, Doménech G, Henrotin Y, Pap T, Richette P, Sawitzke A, du Souich P, Pelletier JP. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis. England; 2016 Jan;75(1):37–44. Epub 2015 Jan 14. PMID: 25589511; PMCID: PMC4717399. DOI: https://doi.org/10.1136/annrheumdis-2014-206792
Provenza JR, Shinjo SK, Silva JM, Peron CRGS, Rocha FAC. Combined glucosamine and chondroitin sulfate, once or three times daily, provides clinically relevant analgesia in knee osteoarthritis. Clin Rheumatol. 2015 Aug;34(8):1455–62. PMID: 25085275. DOI: https://doi.org/10.1007/s10067-014-2757-1
Persiani S, Roda E, Rovati LC, Locatelli M, Giacovelli G, Roda A. Glucosamine oral bioavailability and plasma pharmacokinetics after increasing doses of crystalline glucosamine sulfate in man. Osteoarthritis and Cartilage. 2005 Dec 1;13(12):1041–9. Epub 2005 Sep 13. DOI: https://doi.org/10.1016/j.joca.2005.07.009
Pazit L, Jeremy D, Nancy B, Michael B, George E, Hill KD. Safety and feasibility of high speed resistance training with and without balance exercises for knee osteoarthritis: a pilot randomised controlled trial. Physical Therapy in Sport. 2018 Nov 1;34:154–63. Epub 2018 Oct 3. DOI: https://doi.org/10.1016/j.ptsp.2018.10.001
Cheung C, Wyman JF, Resnick B, Savik K. Yoga for managing knee osteoarthritis in older women: a pilot randomized controlled trial. BMC Complementary and Alternative Medicine. 2014 May 18;14(1):160. Epub 2014 May 18. DOI: https://doi.org/10.1186/1472-6882-14-160
Chang TF, Liou TH, Chen CH, Huang YC, Chang KH. Effects of elastic-band exercise on lower-extremity function among female patients with osteoarthritis of the knee. Disability and Rehabilitation. Taylor & Francis. 2012 Oct 1;34(20):1727–35. Epub 2012 Mar 8. DOI: https://doi.org/10.3109/09638288.2012.660598
Samut G, Dinçer F, Özdemir O. The effect of isokinetic and aerobic exercises on serum interleukin-6 and tumor necrosis factor alpha levels, pain, and functional activity in patients with knee osteoarthritis. Modern Rheumatology. 2015 Sep 8;25(6):919–24. Epub 2015 May 27. DOI: https://doi.org/10.3109/14397595.2015.1038425
Poolsup N, Suthisisang C, Channark P, Kittikulsuth W. Glucosamine long-term treatment and the progression of knee osteoarthritis: systematic review of randomized controlled trials. Ann Pharmacother. 2005 Jun;39(6):1080–7. Epub 2005 Apr 26. PMID: 15855241. DOI: https://doi.org/10.1345/aph.1E576
Pavelká K, Gatterová J, Olejarová 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 Oct 14;162(18):2113–23. PMID: 12374520. DOI: https://doi.org/10.1001/archinte.162.18.2113
Palazzo C, Nguyen C, Lefevre-Colau MM, Rannou F, Poiraudeau S. Risk factors and burden of osteoarthritis. Annals of Physical and Rehabilitation Medicine. 2016 Jun 1;59(3):134–8. Epub 2016 Feb 9. DOI: https://doi.org/10.1016/j.rehab.2016.01.006
Knoop J, van der Leeden M, Thorstensson CA, Roorda LD, Lems WF, Knol DL, Steultjens MPM, Dekker J. Identification of phenotypes with different clinical outcomes in knee osteoarthritis: data from the Osteoarthritis Initiative. Arthritis Care Res (Hoboken). 2011 Nov;63(11):1535–42. PMID: 21954070. DOI: https://doi.org/10.1002/acr.20571
Tschon M, Contartese D, Pagani S, Borsari V, Fini M. Gender and Sex Are Key determinants in osteoarthritis not only confounding variables. A systematic review of clinical data. J Clin Med. 2021 Jul 19;10(14):3178. Epub 2021 Jul 19. PMID: 34300344; PMCID: PMC8303951. DOI: https://doi.org/10.3390/jcm10143178
Simental-Mendía M, Sánchez-García A, Vilchez-Cavazos F, Acosta-Olivo CA, Peña-Martínez VM, Simental-Mendía LE. Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials. Rheumatol Int. 2018 Aug;38(8):1413–28. Epub 2018 Jun 11. PMID: 29947998. DOI: https://doi.org/10.1007/s00296-018-4077-2
Runge N, Aina A, May S. The benefits of adding manual therapy to exercise therapy for improving pain and function in patients with knee or hip osteoarthritis: a systematic review with meta-analysis. J Orthop Sports Phys Ther. 2022 Oct;52(10):675-A13. Epub 2022 Jul 26. PMID: 35881705. DOI: https://doi.org/10.2519/jospt.2022.11062

How to Cite

Čeh, T., & Šarabon, N. (2023). Effects of adding glucosamine or glucosamine combined with chondroitin to exercise on pain and physical function in adults with knee osteoarthritis: a systematic review and meta-analysis. European Journal of Translational Myology, 33(4). https://doi.org/10.4081/ejtm.2023.12013