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Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)
Medwave2017;17(Suppl2):e6929 doi: 10.5867/medwave.2017.6929
Is chondroitin sulfate effective for osteoarthritis?
Valentina Rojas-Briones, Stephanie Harrison-Muñoz, Sebastián Irarrázaval
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Abstract

Osteoarthritis is the most prevalent chronic articular disease, in which pain is one of the main symptoms and the major determinant of functional loss. Several therapeutic options have been proposed, including chondroitin sulfate, but its actual usefulness has not yet been established. To answer this question we searched in Epistemonikos database, which is maintained by screening multiple information sources. We identified 13 systematic reviews including 50 randomized trials overall. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded it is not clear whether the use of chondroitin sulfate leads to an improvement in pain or functionality in osteoarthritis because the certainty of the evidence is very low.


 
Problem

Osteoarthritis is the most prevalent chronic joint disease in the world, and is associated with progressive and chronic joint cartilage damage, producing pain and limiting the functionality of patients.

One of the drugs available for the management of osteoarthritis is chondroitin sulfate, which in in vitro models has beneficial effects in the metabolism of chondrocytes, synoviocytes and subchondral bone cells, increasing the synthesis of type II collagen and proteoglycan, decreasing the production of inflammatory mediators and proteases, slowing cell death and improving the anabolic-catabolic balance of the cartilage extracellular matrix. Even so, results of its effects differ in clinical trials. Chondroitin sulfate is recommended as a slow-acting drug for osteoarthritis in some international guidelines, while other guidelines do not recommend it or just for certain conditions.

Methods

We used Epistemonikos database, which is maintained by screening multiple information sources, to identify systematic reviews and their included primary studies. With this information we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

  • It is not clear whether the use of chondroitin sulfate leads to an improvement in pain or functionality in osteoarthritis because the certainty of the evidence is very low. 
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

We identified 13 systematic reviews [1],[2],[3],[4],[5],[6], [7],[8],[9],[10],[11],[12],[13] that included 50 randomized controlled trials reported in 53 references [14],[15],[16], [17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27], [28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38], [39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49], [50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60], [61],[62],[63],[64],[65],[66].

What types of patients were included

Four trials included outpatients [21],[52],[54],[66]. The rest of the trials did not provide this information.

Thirty eight trials included patients with knee osteoarthritis [14],[15],[17],[19],[20],[21],[22],[24],[25],[26],[27], [28],[29],[31],[38],[39],[41],[42],[43],[44],[45],[46], [48],[50],[51],[52],[53],[54],[55],[56],[57],[60],[61], [62],[63],[64],[65],[66]. Two trials included hip osteoarthritis [16] and [23], four included hand osteoarthiritis [35],[37],[40],[58], three trials included osteoarthritis in more than one joint [18],[32],[33] an three trials did not provide this information [30],[36],[59].

What types of interventions were included

All of the trials used chondroitin sulfate.

Twenty seven trials used only chondroitin sulfate: [14], [15],[16],[17],[18],[20],[21],[22],[23],[24],[26],[27], [28],[31],[37],[41],[46],[48],[50],[54],[55],[56],[58], [61],[63],[65],[66], eleven trials used chondroitin sulfate and glucosamine [30],[34],[39],[42],[43],[44],[45],[51], [52],[53],[57], five trials used chondroitin sulfate, glucosamine and other components [29],[38],[59],[60], [62], four trials used chondroitin sulfate versus nonsteroidal anti-inflammatory drugs [18],[25],[35],[40] and three trials used chondroitin and did not inform the comparator (no placebo) [33],[36],[64].

Twenty trials used a daily dose of chondroitin sulfate greater than 1000 mg (between 1000 mg and 2000 mg) [16],[17],[18],[19],[21],[25],[28],[31],[36],[37],[48], [50],[51],[53],[56],[57],[59],[63],[64],[66], nineteen trials used a daily dose of chondroitin sulfate lesser than 1000 mg (between 60 mg and 800 mg) [20],[22],[23], [24],[26],[29],[34],[35],[39],[40],[41],[46],[54],[55], [58],[60],[61],[62],[65], seven trials used a dose scheme with more than one dose of chondroitin sulfate [27],[30],[33],[42],[43],[44],[45] and four trials did not provide this data [14],[15],[38],[52].

Forty seven trials used oral administration of chondroitin sulfate [16],[17],[18],[19],[20],[21],[22],[23],[24],[25], [26],[27],[28],[29],[30],[31],[33],[34],[35],[36],[37], [39],[40],[41],[42],[43],[44],[45],[46],[48],[50],[51],
[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62], [63],[64],[65],[66], two trials used intramuscular administration [14],[15] and one trial used topical administration [38].

Nine trials reported that patients received coadjuvant therapy with acetaminophen [17],[19],[20],[26],[27],[28], [48],[56],[66]. Fourteen trials used ibuprofen, diclofenac or other nonsteroidal anti-inflammatory drugs [14],[25],[35],[36],[38],[40],[42],[43],[44],[52],[59],[60],
[62],[63]. The rest of the trials did not provide information on the use of other drugs besides chondroitin sulfate.

The treatment mean time of duration was 7 months, with a minimum of 1 month and a maximum of 2 years. Eight trials did not report this data [25],[26],[27], [29],[35],[36],[40],[56].

Thirty-seven trials compared against placebo: [14],[15], [16],[17],[18],[20],[21],[22],[23],[24],[26],[27],[28], [29],[30],[31],[34],[37],[38],[39],[41],[46],[48],[50], [51],[52],[54],[55],[56],[58],[59],[60],[61],[62],[63], [65],[66]. Ten trials compared against nonsteroidal anti-inflammatory drugs [19],[25],[35],[40],[42],[43],[44], [45],[53],[57]. Three trials did not provide this information (no placebo) [33],[36],[64].

What types of outcomes
were measured

Among the outcomes measured by the systematic reviews were pain in the visual analogue scale (VAS) from 0 to 10 or from 0 to 100 mm, the Western Ontario and McMaster Universities Total Arthritis Index (WOMAC), WOMAC stiffness, Physical Function from 0 to 100 (adapted WOMAC scale), Lequesne Index, reduction of joint space in the radiography, adverse effects, total knee arthroplasty requirement, among others.
Summary of findings

The effects of chondroitin sulfate are based on 18 randomized trials that, in total, included 2188 patients. The rest of the trials did not report the outcomes of interest, or the identified reviews do not provide data suitable for meta-analysis. Eighteen trials [14],[16],[17],[18],[21],[22],[23],[24],[27],[31],[32],[41],[46],[50],[56],[61],[63],[66] measured pain using the visual analogue scale (2188 patients). Only two trials [24],[26] evaluated functionality using the WOMAC scale (403 patients). Adverse effects were obtained directly from one of the systematic reviews identified [13], since it was not possible to extract more information from the other reviews. The summary of findings is as follows:

  • It is not clear whether chondroitin sulfate decreases pain in osteoarthritis because the certainty of the evidence is very low.
  • It is not clear whether chondroitin sulfate improves functionality in osteoarthritis because the certainty of the evidence is very low.
  • Chondroitin sulfate has no adverse effects or they are minimal. The certainty of the evidence is high.

Other considerations for decision-making

To whom this evidence does and does not apply
  • Although the intention of this summary was to encompass all possible joints that suffer from osteoarthritis and the respective treatment outcome with chondroitin sulfate, most of the primary studies focus on knee osteoarthritis. However, in the absence of direct evidence for other joints, it is reasonable to extrapolate the conclusions of this summary. Therefore, we think the evidence presented in this summary is broadly applicable to patients with all types of osteoarthritis. 
About the outcomes included in this summary
  • The chosen outcomes were pain and functionality because they are critical outcomes for decision-making on the use of chondroitin sulfate. This selection is based on the opinion of the authors of this summary, but it agrees in general with the outcomes mentioned by the systematic reviews and clinical guidelines.
  • No radiological outcomes were selected because they are surrogate outcomes and do not necessarily predict clinical outcomes.
Balance between benefits and risks, and certainty of the evidence
  • It is not possible to make an appropriate balance between benefits and risks because of the uncertainty about benefits.
What would patients and their doctors think about this intervention
  • Faced with the evidence presented in this summary, most patients and clinicians should lean against the use of this intervention.
  • However, in the absence of clearly effective therapeutic alternatives, there may be variability in clinical decisions made by individual patients. Those who put more value on the possible benefit, even if it is not proven, could lean in favor of the intervention. Those who privilege the certainty of the evidence or the costs, would possibly lean against.
  • There should be less variability in the decisions made by clinicians given the recommendations against the use of this intervention in the main guidelines.
Resource considerations
  • It is not possible to make an appropriate balance between benefits and costs because of the uncertainty about benefits.

Differences between this summary and other sources
  • On the matter of the information given by the systematic reviews, four of them [1],[3],[4],[11] report that chondroitin sulfate would be beneficial for either of the two critical outcomes (pain and functionality), although some highlight the high risk of bias. In contrast, two reviews [5],[6] indicate that it would not be beneficial for any of the aforementioned outcomes. On the other hand, five systematic reviews [7],[8],[9],[10],[12] did not explore clinically relevant outcomes, instead only analysed surrogate outcomes.
  • Finally, our summary leads to a conclusion slightly different from that of the Cochrane review [13], which is the most recent and complete of the reviews identified. This indicates that chondroitin sulfate has a small to moderate positive effect compared to placebo in reducing pain, and that it has a low risk of serious adverse effects.
  • In respect to the international guidelines for osteoarthritis, the one from the Osteoarthritis Research Society International (OARSI) [67] states that the use of chondroitin sulfate for symptom management has an uncertain result and that its use is not appropriate to modify the disease, which is consistent with the results of this summary. The guidelines of the American Academy of Orthopedic Surgeons (AAOS) [68] do not recommend the use of chondroitin sulfate for patients with symptomatic knee osteoarthritis.
Could this evidence change in the future?
  • The probability that future research changes the conclusions of this summary is very high, due to the uncertainty of the current evidence.
  • There are at least ten ongoing randomized trials [69],[70],[71],[72][73],[74],[75],[76],[77],[78] evaluating the use of chondroitin sulfate in osteoarthritis compared to placebo according to the International Clinical Trials Registry Platform of the World Health Organization.
How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Chondroitin sulfate for osteoarthritis

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

La artrosis es la enfermedad articular crónica que presenta mayor prevalencia, en la cual el dolor es uno de los principales síntomas y el mayor determinante de la pérdida de funcionalidad. Se han planteado múltiples opciones terapéuticas, entre ellas el condroitín sulfato, pero su real utilidad aún no ha sido claramente demostrada. Para aclarar esta interrogante utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples fuentes de información. Identificamos 13 revisiones sistemáticas que en conjunto incluyen 50 estudios aleatorizados que responden la pregunta de este resumen. Extrajimos la información relevante, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que no está claro si el uso de condroitín sulfato produce una mejoría en el dolor o la funcionalidad en la artrosis porque la certeza de la evidencia es muy baja.

Authors: Valentina Rojas-Briones[1,2], Stephanie Harrison-Muñoz[1,2], Sebastián Irarrázaval[2,3]

Affiliation:
[1] Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[2] Proyecto Epistemonikos, Santiago, Chile
[3] Proyecto Epistemonikos, Santiago, Chile

E-mail: sirarraz@med.puc.cl

Author address:
[1] Escuela de Medicina
Pontificia Universidad Católica de Chile
Diagonal Paraguay 362
Oficina 310
Santiago Centro
Chile

Citation: Rojas-Briones V, Harrison-Muñoz S, Irarrázaval S. Is chondroitin sulfate effective for osteoarthritis?. Medwave2017;17(Suppl2):e6929 doi: 10.5867/medwave.2017.6929

Submission date: 30/12/2016

Acceptance date: 30/12/2016

Publication date: 26/4/2017

PubMed record

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  56. Pavelka K, Coste P, Géher P, Krejci G. Efficacy and safety of piascledine 300 versus chondroitin sulfate in a 6 months treatment plus 2 months observation in patients with osteoarthritis of the knee. Clin Rheumatol. 2010 Jun;29(6):659-70 | CrossRef | PubMed |
  57. Sawitzke AD, Shi H, Finco MF, Dunlop DD, Harris CL, Singer NG, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis. 2010 Aug;69(8):1459-64 | CrossRef | PubMed |
  58. Gabay C, Medinger-Sadowski C, Gascon D, Kolo F, Finckh A. Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial at a single center. Arthritis Rheum. 2011 Nov;63(11):3383-91 | CrossRef | PubMed |
  59. Magrans-Courtney T, Wilborn C, Rasmussen C, Ferreira M, Greenwood L, Campbell B, et al. Effects of diet type and supplementation of glucosamine, chondroitin, and MSM on body composition, functional status, and markers of health in women with knee osteoarthritis initiating a resistance-based exercise and weight loss program. J Int Soc Sports Nutr. 2011 Jun 20;8(1):8 | CrossRef | PubMed |
  60. Nakasone Y, Watabe K, Watanabe K, Tomonaga A, Nagaoka I, Yamamoto T, et al. Effect of a glucosamine-based combination supplement containing chondroitin sulfate and antioxidant micronutrients in subjects with symptomatic knee osteoarthritis: A pilot study. Exp Ther Med. 2011 Sep;2(5):893-899 | PubMed |
  61. Wildi LM, Raynauld JP, Martel-Pelletier J, Beaulieu A, Bessette L, Morin F, et al. Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI. Ann Rheum Dis. 2011 Jun;70(6):982-9 | CrossRef | PubMed |
  62. Kanzaki N, Saito K, Maeda A, Kitagawa Y, Kiso Y, Watanabe K, et al. Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled study. J Sci Food Agric. 2012 Mar 15;92(4):862-9 | CrossRef | PubMed |
  63. Railhac JJ, Zaim M, Saurel AS, Vial J, Fournie B. Effect of 12 months treatment with chondroitin sulfate on cartilage volume in knee osteoarthritis patients: a randomized, double-blind, placebo-controlled pilot study using MRI. Clin Rheumatol. 2012 Sep;31(9):1347-57 | CrossRef | PubMed |
  64. Fardellone P, Zaim M, Saurel AS, Maheu E. Comparative efficacy and safety study of two chondroitin sulfate preparations from different origin (avian and bovine) in symptomatic osteoarthritis of the knee. Open Rheumatol J. 2013;7:1-12 | CrossRef | PubMed |
  65. Raynauld JP, Martel-Pelletier J, Dorais M, Haraoui B, Choquette D, Abram F, et al. Total Knee Replacement as a Knee Osteoarthritis Outcome: Predictors Derived from a 4-Year Long-Term Observation following a Randomized Clinical Trial Using Chondroitin Sulfate. Cartilage. 2013 Jul;4(3):219-26 | CrossRef | PubMed |
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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 Feb;60(2):524-33. | CrossRef | PubMed |

Möller I, Pérez M, Monfort J, Benito P, Cuevas J, Perna C, et al. Effectiveness of chondroitin sulphate in patients ith concomitant knee osteoarthritis and psoriasis: a randomized, double-blind, placebo-controlled study. Osteoarthritis Cartilage. 2010 Jun;18 Suppl 1:S32-40 | CrossRef | PubMed |

Pavelka K, Coste P, Géher P, Krejci G. Efficacy and safety of piascledine 300 versus chondroitin sulfate in a 6 months treatment plus 2 months observation in patients with osteoarthritis of the knee. Clin Rheumatol. 2010 Jun;29(6):659-70 | CrossRef | PubMed |

Sawitzke AD, Shi H, Finco MF, Dunlop DD, Harris CL, Singer NG, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis. 2010 Aug;69(8):1459-64 | CrossRef | PubMed |

Gabay C, Medinger-Sadowski C, Gascon D, Kolo F, Finckh A. Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial at a single center. Arthritis Rheum. 2011 Nov;63(11):3383-91 | CrossRef | PubMed |

Magrans-Courtney T, Wilborn C, Rasmussen C, Ferreira M, Greenwood L, Campbell B, et al. Effects of diet type and supplementation of glucosamine, chondroitin, and MSM on body composition, functional status, and markers of health in women with knee osteoarthritis initiating a resistance-based exercise and weight loss program. J Int Soc Sports Nutr. 2011 Jun 20;8(1):8 | CrossRef | PubMed |

Nakasone Y, Watabe K, Watanabe K, Tomonaga A, Nagaoka I, Yamamoto T, et al. Effect of a glucosamine-based combination supplement containing chondroitin sulfate and antioxidant micronutrients in subjects with symptomatic knee osteoarthritis: A pilot study. Exp Ther Med. 2011 Sep;2(5):893-899 | PubMed |

Wildi LM, Raynauld JP, Martel-Pelletier J, Beaulieu A, Bessette L, Morin F, et al. Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI. Ann Rheum Dis. 2011 Jun;70(6):982-9 | CrossRef | PubMed |

Kanzaki N, Saito K, Maeda A, Kitagawa Y, Kiso Y, Watanabe K, et al. Effect of a dietary supplement containing glucosamine hydrochloride, chondroitin sulfate and quercetin glycosides on symptomatic knee osteoarthritis: a randomized, double-blind, placebo-controlled study. J Sci Food Agric. 2012 Mar 15;92(4):862-9 | CrossRef | PubMed |

Railhac JJ, Zaim M, Saurel AS, Vial J, Fournie B. Effect of 12 months treatment with chondroitin sulfate on cartilage volume in knee osteoarthritis patients: a randomized, double-blind, placebo-controlled pilot study using MRI. Clin Rheumatol. 2012 Sep;31(9):1347-57 | CrossRef | PubMed |

Fardellone P, Zaim M, Saurel AS, Maheu E. Comparative efficacy and safety study of two chondroitin sulfate preparations from different origin (avian and bovine) in symptomatic osteoarthritis of the knee. Open Rheumatol J. 2013;7:1-12 | CrossRef | PubMed |

Raynauld JP, Martel-Pelletier J, Dorais M, Haraoui B, Choquette D, Abram F, et al. Total Knee Replacement as a Knee Osteoarthritis Outcome: Predictors Derived from a 4-Year Long-Term Observation following a Randomized Clinical Trial Using Chondroitin Sulfate. Cartilage. 2013 Jul;4(3):219-26 | CrossRef | PubMed |

Zegels B, Crozes P, Uebelhart D, Bruyère O, Reginster JY. Equivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4&6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study. Osteoarthritis Cartilage. 2013 Jan;21(1):22-7 | CrossRef | PubMed |

July 2022, Vol 22, Issue 6
icon Research papers
Association of biomarkers and severity of COVID-19: A crosssectional study

Systematization of initiatives in sexual and reproductive health about good practices criteria in response to the COVID-19 pandemic in primary health care in Chile

Clinical, psychological, social, and family characterization of suicidal behavior in Chilean adolescents: a multiple correspondence analysis

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