SpringerLink
Log in

Efficacy and safety of the combination of glucosamine and chondroitin for knee osteoarthritis: a systematic review and meta-analysis

  • Arthroscopy and Sports Medicine
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Aims

Though glucosamine and chondroitin have become common practices for treating knee osteoarthritis, the clinical value of these two drugs in combination are still questionable. To evaluate the efficacy and safety of the combination of glucosamine (GS) and chondroitin (CS) in knee osteoarthritis (KOA) treatment.

Methods

We searched electronic databases, including PubMed, Embase, Web of Science, SCOPUS, The Cochrane Central Register of Controlled Trials (CENTRAL), OVID, Chinese Clinical Trial Registry (ChiCTR), CBM, CNKI, WanFang and VIP from their inception to August 20, 2020, for literature concerning the combination of glucosamine and chondroitin in knee osteoarthritis treatment. The Cochrane Collaboration’s tool for assessing risk of bias and Jadad scale were used to evaluate the risk of bias and quality of literature. The meta-analysis was performed using Review Manager 5.3 software.

Results

Eight randomized controlled trials (RCTs) were included, including 7 studies in English and 1 study in Chinese. While the number of included papers was quite limited, the number of participants was decent, and quality appraisal result is acceptable. The total number of patients was 3793, with 1067 patients receiving a combination of glucosamine and chondroitin and 2726 patients receiving other treatments. The meta-analysis results revealed the following: (1) Regarding the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, compared with the placebo group, the combination group showed a statistically significant advantage [MD = − 12.04 (− 22.33 ~ − 1.75); P = 0.02], while the other groups showed no significance. (2) Regarding the VAS score, none of the comparisons showed significance. (3) In the secondary outcomes, except the comparison of JSN between the combination and placebo groups (MD = − 0.09 (− 0.18 ~ − 0.00); P = 0.04) and the comparison of the WOMAC stiffness score between the combination and CS groups [MD = − 4.70 (− 8.57 ~ − 0.83); P = 0.02], none of the comparisons showed a significant difference. (4)Safety analysis results show that none of the comparisons have significant differences.

Conclusion

Our study confirmed that the combination of glucosamine and chondroitin is effective and superior to other treatments in knee osteoarthritis to a certain extent. It is worthwhile to popularize and apply the combination in KOA treatment considering the point of effect, tolerability and economic costs. Additionally, regarding the limited number of studies and uneven trial quality, more high-quality trials are required to investigate the accurate clinical advantages of the combination.

PROSPERO registration ID

CRD42020202093.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig.4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Dulay GS, Cooper C, Dennison EM (2015) Knee pain, knee injury, knee osteoarthritis & work. Best Pract Res Clin Rheumatol 29(3):454–461. https://doi.org/10.1016/j.berh.2015.05.005

    Article  Google Scholar 

  2. Sharma L (2021) Osteoarthritis of the knee. N Engl J Med 384(1):51–59. https://doi.org/10.1056/NEJMcp1903768

    Article  CAS  Google Scholar 

  3. Tang X, Wang S, Zhan S, Niu J, Tao K, Zhang Y, Lin J (2016) The prevalence of symptomatic knee osteoarthritis in China: results from the China health and retirement longitudinal study. Arthritis Rheumatol 68(3):648–653. https://doi.org/10.1002/art.39465

    Article  Google Scholar 

  4. Kolasinski SL, Neogi T, Hochberg MC et al (2020) 2019 American college of rheumatology/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken) 72(2):149–162. https://doi.org/10.1002/acr.24131

    Article  Google Scholar 

  5. Goldman L, Schafer AI (2019) Goldman-Cecil medicine, 26th edn. Elsevier, Philadelphia

    Google Scholar 

  6. Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ (2015) Osteoarthritis. Lancet 386(9991):376–387. https://doi.org/10.1016/S0140-6736(14)60802-3

    Article  CAS  Google Scholar 

  7. Hu X, Lai Z, Wang L (2020) Effects of Taichi exercise on knee and ankle proprioception among individuals with knee osteoarthritis. Res Sports Med 28(2):268–278. https://doi.org/10.1080/15438627.2019.1663520

    Article  Google Scholar 

  8. Wallace IJ, Worthington S, Felson DT, Jurmain RD, Wren KT, Maijanen H, Woods RJ, Lieberman DE (2017) Knee osteoarthritis has doubled in prevalence since the mid-20th century. Proc Natl Acad Sci USA 114(35):9332–9336. https://doi.org/10.1073/pnas.1703856114

    Article  CAS  Google Scholar 

  9. Cross M, Smith E, Hoy D et al (2014) The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 73(7):1323–1330. https://doi.org/10.1136/annrheumdis-2013-204763

    Article  Google Scholar 

  10. Martel-Pelletier J, Barr AJ, Cicuttini FM, Conaghan PG, Cooper C, Goldring MB, Goldring SR, Jones G, Teichtahl AJ, Pelletier JP (2016) Osteoarthritis. Nat Rev Dis Primers 2:16072. https://doi.org/10.1038/nrdp.2016.72

    Article  Google Scholar 

  11. Kolasinski SL, Neogi T, Hochberg MC et al (2020) 2019 American college of rheumatology/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Rheumatol 72(2):220–233. https://doi.org/10.1002/art.41142

    Article  Google Scholar 

  12. Osteoporosis Group of Chinese Orthopaedic Association (2018) Chinese guideline for diagnosis and management of osteoarthritis (2018 edition). Chin J Orthop 38(12):705–715. https://doi.org/10.3760/cma.j.issn.0253-2352.2018.12.001

    Article  Google Scholar 

  13. Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12. https://doi.org/10.1016/0197-2456(95)00134-4

    Article  CAS  Google Scholar 

  14. Cumpston M, Li T, Page MJ et al (2019). Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database of Systematic Reviews 2019(10). Art. No.: ED000142. https://doi.org/10.1002/14651858.ED000142

  15. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  Google Scholar 

  16. Fransen M, Agaliotis M, Nairn L et al (2015) Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis 74(5):851–858. https://doi.org/10.1136/annrheumdis-2013-203954

    Article  CAS  Google Scholar 

  17. Sawitzke AD, Shi H, Finco MF et al (2008) 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 58(10):3183–3191. https://doi.org/10.1002/art.23973

    Article  CAS  Google Scholar 

  18. Clegg DO, Reda DJ, Harris CL et al (2006) Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 354(8):795–808. https://doi.org/10.1056/NEJMoa052771

    Article  CAS  Google Scholar 

  19. Roman-Blas JA, Castañeda S, Sánchez-Pernaute O, Largo R, Herrero-Beaumont G, CS/GS Combined Therapy Study Group (2017) 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 69(1):77–85. https://doi.org/10.1002/art.39819

    Article  CAS  Google Scholar 

  20. Tsuji T, Yoon J, Kitano N, Okura T, Tanaka K (2016) Effects of N-acetyl glucosamine and chondroitin sulfate supplementation on knee pain and self-reported knee function in middle-aged and older Japanese adults: a randomized, double-blind, placebo-controlled trial. Aging Clin Exp Res 28(2):197–205. https://doi.org/10.1007/s40520-015-0412-6

    Article  Google Scholar 

  21. Lugo JP, Saiyed ZM, Lane NE (2016) Effectiveness and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J 15:14. https://doi.org/10.1186/s12937-016-0130-8

    Article  CAS  Google Scholar 

  22. Ye Y, Gao X, Yang N (2015) Analysis and appraisal of safety and curative effect of medicine treatment for moderate or severe knee osteoarthritis by double blind and double simulation. Chin J Modern Med 25(13):73–77. https://doi.org/10.3969/j.issn.1005-8982.2015.13.017

    Article  Google Scholar 

  23. Hochberg MC, Martel-Pelletier J, Monfort J et al (2016) Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib. Ann Rheum Dis 75(1):37–44. https://doi.org/10.1136/annrheumdis-2014-206792

    Article  Google Scholar 

  24. Hermann W, Lambova S, Muller-Ladner U (2018) Current treatment options for osteoarthritis. Curr Rheumatol Rev 14(2):108–116. https://doi.org/10.2174/1573397113666170829155149

    Article  CAS  Google Scholar 

  25. Singh JA, Noorbaloochi S, MacDonald R, Maxwell LJ (2015) Chondroitin for osteoarthritis. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD005614.pub2

    Article  Google Scholar 

  26. Bruyère O, Altman RD, Reginster JY (2016) Effectiveness and safety of glucosamine sulfate in the management of osteoarthritis: evidence from real-life setting trials and surveys. Semin Arthritis Rheum 45(4 Suppl):S12–S17. https://doi.org/10.1016/j.semarthrit.2015.11.011

    Article  CAS  Google Scholar 

  27. Volpi N, Mantovani V, Galeotti F, Bianchi D, Straniero V, Valoti E, Miraglia N (2019) Oral bioavailability and pharmacokinetics of nonanimal chondroitin sulfate and its constituents in healthy male volunteers. Clin Pharmacol Drug Dev 8(3):336–345. https://doi.org/10.1002/cpdd.587

    Article  CAS  Google Scholar 

  28. Hjermstad MJ, Fayers PM, Haugen DF, Caraceni A, Hanks GW, Loge JH, Fainsinger R, Aass N, Kaasa S, Collaborative EPCS (2011) Studies comparing numerical rating scales, verbal rating scales, and visual analogue scales for assessment of pain intensity in adults: a systematic literature review. J Pain Symptom Manag 41(6):1073–1093. https://doi.org/10.1016/j.jpainsymman.2010.08.016

    Article  Google Scholar 

  29. Rubio-Terrés C, Grupo del estudio VECTRA (2010) An economic evaluation of chondroitin sulfate and non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis. Data from the VECTRA study. Reumatol Clin 6(4):187–195. https://doi.org/10.1016/j.reuma.2009.12.009

    Article  Google Scholar 

  30. Kahan A, Uebelhart D, De Vathaire F, Delmas PD, Reginster JY (2009) 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 60(2):524–533. https://doi.org/10.1002/art.24255

    Article  CAS  Google Scholar 

  31. Scholtissen S, Bruyère O, Neuprez A et al (2010) Glucosamine sulphate in the treatment of knee osteoarthritis: cost-effectiveness comparison with paracetamol. Int J Clin Pract 64(6):756–762. https://doi.org/10.1111/j.1742-1241.2010.02362.x

    Article  CAS  Google Scholar 

  32. Bruyere O, Pavelka K, Rovati LC, Gatterová J, Giacovelli G, Olejarová M, Deroisy R, Reginster JY (2008) Total joint replacement after glucosamine sulphate treatment in knee osteoarthritis: results of a mean 8-year observation of patients from two previous 3-year, randomised, placebo-controlled trials. Osteoarthr Cartil 16(2):254–260. https://doi.org/10.1016/j.joca.2007.06.011

    Article  CAS  Google Scholar 

  33. Rovati LC, Girolami F, D’Amato M, Giacovelli G (2016) Effects of glucosamine sulfate on the use of rescue non-steroidal anti-inflammatory drugs in knee osteoarthritis: results from the pharmaco-epidemiology of gonarthrosis (PEGASus) study. Semin Arthritis Rheum 45(4 Suppl):S34-41. https://doi.org/10.1016/j.semarthrit.2015.10.009

    Article  CAS  Google Scholar 

  34. Herrero-Beaumont G, Ivorra JA, Del Carmen TM et al (2007) Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum 56(2):555–567. https://doi.org/10.1002/art.22371

    Article  CAS  Google Scholar 

  35. Bruyère O, Cooper C, Pelletier JP et al (2016) A consensus statement on the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) algorithm for the management of knee osteoarthritis-From evidence-based medicine to the real-life setting. Semin Arthritis Rheum 45(4 Suppl):S3-11. https://doi.org/10.1016/j.semarthrit.2015.11.010

    Article  Google Scholar 

  36. Bassleer C, Rovati L, Franchimont P (1998) Stimulation of proteoglycan production by glucosamine sulfate in chondrocytes isolated from human osteoarthritic articular cartilage in vitro. Osteoarthr Cartil 6(6):427–434. https://doi.org/10.1053/joca.1998.0146

    Article  CAS  Google Scholar 

  37. Barclay TS, Tsourounis C, McCart GM (1998) Glucosamine. Ann Pharmacother 32(5):574–579. https://doi.org/10.1345/aph.17235

    Article  CAS  Google Scholar 

  38. Bissett DL (2006) Glucosamine: an ingredient with skin and other benefits. J Cosmet Dermatol 5(4):309–315. https://doi.org/10.1111/j.1473-2165.2006.00277.x

    Article  Google Scholar 

  39. du Souich P, García AG, Vergés J, Montell E (2009) Immunomodulatory and anti-inflammatory effects of chondroitin sulphate. J Cell Mol Med 13(8A):1451–1463. https://doi.org/10.1111/j.1582-4934.2009.00826.x

    Article  CAS  Google Scholar 

  40. Lomonte ABV, Mendonça JA, de Castro BG, Castro ML (2018) Multicenter, randomized, double-blind clinical trial to evaluate effectiveness and safety of combined glucosamine sulfate and chondroitin sulfate capsules for treating knee osteoarthritis. Adv Rheumatol 58(1):41. https://doi.org/10.1186/s42358-018-0041-9

    Article  Google Scholar 

  41. Thie NM, Prasad NG, Major PW (2001) Evaluation of glucosamine sulfate compared to ibuprofen for the treatment of temporomandibular joint osteoarthritis: a randomized double blind controlled 3 month clinical trial. J Rheumatol 28(6):1347–1355. https://doi.org/10.1097/00124743-200106000-00019

    Article  CAS  Google Scholar 

  42. Simental-Mendía M, Sánchez-García A, Vilchez-Cavazos F, Acosta-Olivo CA, Peña-Martínez VM, Simental-Mendía LE (2018) Effect of glucosamine and chondroitin sulfate in symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials. Rheumatol Int 38(8):1413–1428. https://doi.org/10.1007/s00296-018-4077-2

    Article  CAS  Google Scholar 

  43. Karcioglu O, Topacoglu H, Dikme O, Dikme O (2018) A systematic review of the pain scales in adults: which to use? Am J Emerg Med 36(4):707–714. https://doi.org/10.1016/j.ajem.2018.01.008

    Article  Google Scholar 

  44. Angst F, Aeschlimann A, Stucki G (2001) Smallest detectable and minimal clinically important differences of rehabilitation intervention with their implications for required sample sizes using WOMAC and SF-36 quality of life measurement instruments in patients with osteoarthritis of the lower extremities. Arthritis Rheum 45(4):384–391. https://doi.org/10.1002/1529-0131(200108)45:4%3c384::AID-ART352%3e3.0.CO;2-0

    Article  CAS  Google Scholar 

  45. Tubach F, Ravaud P, Martin-Mola E et al (2012) Minimum clinically important improvement and patient acceptable symptom state in pain and function in rheumatoid arthritis, ankylosing spondylitis, chronic back pain, hand osteoarthritis, and hip and knee osteoarthritis: results from a prospective multinational study. Arthritis Care Res (Hoboken) 64(11):1699–1707. https://doi.org/10.1002/acr.21747

    Article  CAS  Google Scholar 

  46. Hmamouchi I, Allali F, Tahiri L et al (2012) Clinically important improvement in the WOMAC and predictor factors for response to non-specific non-steroidal anti-inflammatory drugs in osteoarthritic patients: a prospective study. BMC Res Notes 23(5):58. https://doi.org/10.1186/1756-0500-5-58

    Article  CAS  Google Scholar 

  47. Harris JD, Brand JC, Cote MP, Faucett SC, Dhawan A (2017) Research pearls: the significance of statistics and perils of pooling. Part 1: clinical versus statistical significance. Arthroscopy 33(6):1102–1112. https://doi.org/10.1016/j.arthro.2017.01.053

    Article  Google Scholar 

  48. Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY (2003) Structural and symptomatic effectiveness of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 163(13):1514–1522. https://doi.org/10.1001/archinte.163.13.1514

    Article  CAS  Google Scholar 

  49. Zhu X, Sang L, Wu D, Rong J, Jiang L (2018) Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials. J Orthop Surg Res 13:170. https://doi.org/10.1186/s13018-018-0871-5

    Article  Google Scholar 

Download references

Funding

No funds, grants, or other support was received.

Author information

Author notes

  1. Zhengyuan Meng and Jiakun Liu have contributed equally to this article, and are joint first authors.

Authors and Affiliations

  1. Zhengzhou University Medical College, Zhengzhou, Henan, People’s Republic of China

    Zhengyuan Meng

  2. Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China

    Jiakun Liu

  3. Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, Henan, 450052, People’s Republic of China

    Nan Zhou

Authors
  1. Zhengyuan Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiakun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nan Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nan Zhou.

Ethics declarations

Conflict of interest

The authors declare they have no conflicts of interest. There was no funding source for this study. This article does not contain any studies with human participants or animals performed by any of the authors. This study was IRB exempt; informed consent from individual participants did not apply to the study methods. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Ethical approval

Not applicable.

Informed consent

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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 143, 409–421 (2023). https://doi.org/10.1007/s00402-021-04326-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00402-021-04326-9

Keywords

Search

Navigation