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.
Kahan, Andre; Uebelhart, Daniel; De Vathaire, Florentet al.
2009 • In Arthritis and Rheumatism, 60 (2), p. 524-33
[en] OBJECTIVE: To assess the long-term effects of chondroitins 4 and 6 sulfate (CS) on the radiographic progression of, and symptom changes associated with, knee osteoarthritis (OA). METHODS: We performed an international, randomized, double-blind, placebo-controlled trial in which 622 patients with knee OA were randomly assigned to receive either 800 mg CS (n = 309 patients) or placebo (n = 313 patients) once daily for 2 years. Radiographs of the target knee, using the Lyon schuss view, were obtained at the time of enrollment and at 12, 18, and 24 months. The minimum joint space width (JSW) of the medial compartment of the tibiofemoral joint was assessed by digital image analysis. The primary outcome was the loss in minimum JSW over 2 years. RESULTS: The intent-to-treat analysis demonstrated a significant reduction (P < 0.0001) in minimum JSW loss in the CS group (mean +/- SEM -0.07 +/- 0.03 mm) as compared with the placebo group (-0.31 +/- 0.04 mm). The percentage of patients with radiographic progression > or =0.25 mm was significantly reduced in the CS group compared with the placebo group (28% versus 41% [P < 0.0005]; relative risk reduction 33% [95% confidence interval 16-46%]). The number of patients needed to treat was 8 (95% confidence interval 5-17). Pain improved significantly faster in the CS group than in the placebo group (P < 0.01). There were no differences in safety between groups. CONCLUSION: The long-term combined structure-modifying and symptom-modifying effects of CS suggest that it could be a disease-modifying agent in patients with knee OA.
Disciplines :
Rheumatology
Author, co-author :
Kahan, Andre
Uebelhart, Daniel
De Vathaire, Florent
Delmas, Pierre D
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Language :
English
Title :
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.
Publication date :
2009
Journal title :
Arthritis and Rheumatism
ISSN :
0004-3591
eISSN :
1529-0131
Publisher :
Wiley Liss, Inc., New York, United States - New York
Emrani PS, Katz JN, Kessler CL, Reichmann WM, Wright EA, McAlindon TE, et al. Joint space narrowing and Kellgren-Lawrence progression in knee osteoarthritis: an analytic literature synthesis. Osteoarthritis Cartilage 2008;16:873-82.
Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998;41:778-99.
American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum 2000;43:1905-15.
Pendleton A, Arden N, Dougados M, Doherty M, Bannwarth B, Bijlsma JW, et al. 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 2000;59:936-44.
Lequesne M, Brandt K, Bellamy N, Moskowitz R, Menkes CJ, Pelletier JP, et al. Guidelines for testing slow acting drugs in osteoarthritis [published erratum appears in J Rheumatol Suppl 1994;21:2395]. J Rheumatol Suppl 1994;41:65-71.
Group for the Respect of Ethics and Excellence in Science (GREES): osteoarthritis section. Recommendations for the registration of drugs used in the treatment of osteoarthritis. Ann Rheum Dis 1996;55:552-7.
Altman R, Brandt K, Hochberg M, Moskowitz R. Design and conduct of clinical trials of patients with osteoarthritis: recommendations from a task force of the Osteoarthritis Research Society. Osteoarthritis Cartilage 1996;4:217-43.
Dougados M, Nguyen M, Berdah L, Mazieres B, Vignon E, Lequesne M, for the ECHODIAH Investigators Study Group. Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a 3-year, placebo-controlled trial. Arthritis Rheum 2001;44:2539-47.
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;357:251-6.
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;162:2113-23.
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;52:779-86.
Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum 1986;29:1039-49.
Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis 1957;16:494-502.
Hellio le Graverand MP, Vignon EP, Brandt KD, Mazzuca SA, Piperno M, Buck R, et al. Head-to-head comparison of the Lyon schuss and fixed flexion radiographic techniques: long-term reproducibility in normal knees and sensitivity to change in osteoarthritic knees. Ann Rheum Dis 2008;67:1562-6.
Reginster JY, Kahan A, Vignon E. A two-year prospective, randomized, double-blind, controlled study assessing the effect of chondroitin 4&6 sulfate (CS) on the structural progression of knee osteoarthritis: STOPP (STudy on Osteoarthritis Progression Prevention) [abstract]. Arthritis Rheum 2006;54:4117.
Arlot M, Gensburger D, Roux JP, Delmas PD. Does the knowledge of the time sequence of radiographs impact the reading of radiographs in longitudinal studies in patients with knee osteoarthritis? Osteoporos Int 2008;19 Suppl 1:59.
Altman RD, Abadie E, Avouac B, Bouvenot G, Branco J, Bruyere O, et al, for the Group for the Respect of Excellence and Ethics in Science (GREES). Total joint replacement of hip or knee as an outcome measure for structure modifying trials in osteoarthritis. Osteoarthritis Cartilage 2005;13:13-9.
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 anti-rheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833-40.
Abadie E, Ethgen D, Avouac B, Bouvenot G, Branco J, Bruyere O, et al, on behalf of the Group for the Respect of Excellence and Ethics in Science (GREES). Recommendations for the use of new methods to assess the efficacy of disease-modifying drugs in the treatment of osteoarthritis. Osteoarthritis Cartilage 2004;12:263-8.
Conrozier T, Mathieu P, Piperno M, Favret H, Colson F, Vignon M, et al. Selection of knee radiographs for trials of structure-modifying drugs in patients with knee osteoarthritis: a prospective, longitudinal study of Lyon schuss knee radiographs with the definition of adequate alignment of the medial tibial plateau. Arthritis Rheum 2005;52:1411-7.
Piperno M, Hellio le Graverand MP, Conrozier T, Bochu M, Mathieu P, Vignon E. Quantitative evaluation of joint space width in femorotibial osteoarthritis: comparison of three radiographic views. Osteoarthritis Cartilage 1998;6:252-9.
Mazzuca SA, Brandt KD, Katz BP. Is conventional radiography suitable for evaluation of a disease-modifying drug in patients with knee osteoarthritis? Osteoarthritis Cartilage 1997;5:217-26.
Dieppe PA, Cushnaghan J, Shepstone L. The Bristol 'OA500' Study: progression of osteoarthritis (OA) over 3 years and the relationship between clinical and radiographic changes at the knee joint. Osteoarthritis Cartilage 1997;5:87-97.
McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469-75.
Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis. Arch Intern Med 2003;163:1514-22.
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;354:795-808.
Pham T, van der Heijde D, Altman RD, Anderson JJ, Bellamy N, Hochberg M, et al. OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage 2004;12:389-99.
Uebelhart D, Malaise M, Marcolongo R, de Vathaire F, Piperno M, Mailleux E, et al. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage 2004;12:269-76.
Volpi N. Chondroitin sulphate for the treatment of osteoarthritis. Curr Med Chem Anti-Inflam Anti-Allergy Agents 2005;4:221-34.
Uebelhart D, Thonar EJ, Zhang J, Williams JM. Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit. Osteoarthritis Cartilage 1998;6 Suppl A:6-13.
Monfort J, Pelletier JP, Garcia-Giralt N, Martel-Pelletier J. Biochemical basis of the effect of chondroitin sulfate on osteoarthritis articular tissues. Ann Rheum Dis 2008;67:735-40.
Volpi N. Oral bioavailability of chondroitin sulfate (Condrosulf) and its constituents in healthy male volunteers. Osteoarthritis Cartilage 2002;10:768-77.
Maillefert JF, Gueguen A, Nguyen M, Berdah L, Lequesne M, Mazieres B, et al. Relevant change in radiological progression in patients with hip osteoarthritis. I. Determination using predictive validity for total hip arthroplasty. Rheumatology (Oxford) 2002;41:142-7.
Bruyere O, Compere S, Rovati LC, Giacovelli G, Deroisy R, Reginster JY. Five-year follow-up of patients from a previous 3-year randomized, controlled trial of glucosamine sulfate in knee osteoarthritis [abstract]. Arthritis Rheum 2003;48 Suppl 9:S80.
Bruyere O, Pavelka K, Rovati LC, Gatterova J, Giacovelli G, Olejarova M, et al. 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. Osteoarthritis Cartilage 2008;16:254-60.