Additive effects of glucosamine or risedronate for the treatment of osteoarthritis of the knee combined with home exercise: a prospective randomized 18-month trial

  • Takayuki Kawasaki
  • Hisashi Kurosawa
  • Hiroshi Ikeda
  • Sung-gon Kim
  • Aki Osawa
  • Yuji Takazawa
  • Mitsuaki Kubota
  • Muneaki Ishijima
Original Article


We have previously demonstrated the efficacy of therapeutic exercise for osteoarthritis (OA) of the knee. This study was performed to examine the additive effects of glucosamine or risedronate on the exercise therapy. In this study, 142 female patients with moderate OA of the knee, who had been recommended to undergo home exercise at the first visit to the hospital, were randomly given glucosamine hydrochloride, risedronate, or no additive. Although improvement after 18 months was observed in all groups using individual scales for evaluation of pain and function of the knee, no significant differences were observed between the groups regarding any of the scales, indicating no significant additive effect of glucosamine or risedronate. One reason for the lack of effect of glucosamine or risedronate on OA of the knee may be that the effect of these agents was occluded by the effect of therapeutic exercise to improve pain and function of the knee. This finding means that even if glucosamine and risedronate were to have an effect on OA of the knee, the effect would not be greater than the effect of knee exercise to improve the symptoms.

Key words

osteoarthritis glucosamine risedronate home exercise treatment 


  1. 1.
    Radin EL, Paul IL, Rose RM (1972) Mechanical factors in osteoarthritis. Lancet 1:519–522PubMedCrossRefGoogle Scholar
  2. 2.
    Radin EL, Parker HG, Pugh JW, Steinberg RS, Paul IL, Mose RM (1973) Response of joints to impact loading. III. Relationship between trabecular microfractures and cartilage degeneration. J Biomech 6:51–57PubMedCrossRefGoogle Scholar
  3. 3.
    Brown TD, Radin EL, Martin RB, Burr DB (1984) Finite element studies of some juxtarticular changes due to localized subchondral stiffening. J Biomech 17:11–24PubMedCrossRefGoogle Scholar
  4. 4.
    O’Reilley SC, Muir KR, Doherty M (1999) Effectiveness of home exercise on pain and disability from osteoarthritis of the knee. Ann Rheum Dis 58:15–19Google Scholar
  5. 5.
    Deyle GD, Henderson NE, Matekel RL, Ryder MG, Garber MB, Allison SC (2000) Effectiveness of manual physical therapy and exercise in osteoarthritis of the knee. Ann Intern Med 132:173–181PubMedGoogle Scholar
  6. 6.
    Petrella RJ, Bartha C (2000) Home based exercise therapy for older patients with knee osteoarthritis: a randomized clinical trial. J Rheumatol 27:2215–2221PubMedGoogle Scholar
  7. 7.
    Penninx BW, Messier SP, Rejeski WJ, Williamson JD, DiBari M, Cavazzini C, Applegate WB, Pahor M (2001) Physical exercise and the prevention of disability in activities of daily living in older persons with osteoarthritis. Arch Intern Med 161:2309–2316PubMedCrossRefGoogle Scholar
  8. 8.
    Kurosawa H, Ikeda H, Kim S, Osawa A, Seto H, Takazawa Y (2006) Conservative treatment for osteoarthritis of the knee: with special reference to survival rate of home-based exercise (in Japanese). Nippon Seikeigeka Gakkai Zasshi (J Jpn Orthop Assoc) 80:933–941Google Scholar
  9. 9.
    Kurosawa H (2005) Conservative treatment for osteoarthritis of the knee by home exercise (in Japanese). Nippon Seikeigeka Gakkai Zasshi (J Jpn Orthop Assoc) 79:793–805Google Scholar
  10. 10.
    Kurosawa H (2006) Effect of therapeutic exercise for osteoarthritis of the knee (in Japanese). Rinsyo Seikeigeka 41:739–747Google Scholar
  11. 11.
    Hanypsiak BT, Shaffer BS (2005) Nonoperative treatment of unicompartmental arthritis of the knee. Orthop Clin N Am 36:401–411CrossRefGoogle Scholar
  12. 12.
    McAlindon TE, Beth Anne Biggee BA (2005) Nutritional factors and osteoarthritis: recent developments. Curr Opin Rheumatol 17:647–652PubMedGoogle Scholar
  13. 13.
    Reginster JY, Deroisy R, Rovati LC, Lee RL, Lejeune E, Bruyere O, Giacovelli G, Henrotin Y, Dacre JE, Gossett C (2001) Longterm effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 357:251–256PubMedCrossRefGoogle Scholar
  14. 14.
    Pavelka K, Gatterova J, Olejarova M, Machacek S, Giacovelli G, Rovati LC (2002) Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, doubleblind study. Arch Intern Med 162:2113–2123PubMedCrossRefGoogle Scholar
  15. 15.
    Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, Blanco FJ, Benito P, Martín-Mola E, Paulino J, Marenco J, Porto A, Laffon A, Araújo D, Figueroa M, Branco J (2007) Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side com parator. Arthritis Rheum 56:555–567PubMedCrossRefGoogle Scholar
  16. 16.
    Hua J, Sakamoto K, Nagaoka I (2002) Inhibitory actions of glucosamine, a therapeutic agent for osteoarthritis, on the functions of neutrophils. J Leukoc Biol 71:632–640PubMedGoogle Scholar
  17. 17.
    Tamai Y, Miyatake K, Okamoto Y, Takamori T, Sakamoto K, Minami S (2002) Enhanced healing of cartilaginous injuries by glucosamine hydrochloride. Carbohydr Polym 48:369–378CrossRefGoogle Scholar
  18. 18.
    Dodge GR, Jimenez SA (2003) Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes. Osteoarthritis Cartilage 11:424–432PubMedCrossRefGoogle Scholar
  19. 19.
    Byron CR, Orth MW, Venta PJ, Lloyd JW, Caron JP (2003) Influence of glucosamine on matrix metalloproteinase expression and activity in lipopolysaccharide-stimulated equine chondrocytes. Am J Vet Res 64:666–671PubMedCrossRefGoogle Scholar
  20. 20.
    Tamai Y, Miyatake K, Okamoto Y, Takamori T, Sakamoto K, Minami S (2003) Enhanced healing of cartilaginous injuries by N-acetyl-D-glucosamine and glucuronic acid. Carbohydr Polym 54:251–262CrossRefGoogle Scholar
  21. 21.
    Wang SX, Cherian A, Dumitriu M, Grynpas MD, Carran J, Wainman D, Anastassiades T (2007) Disease modifying effects of N-butyryl glucosamine in a streptococcal cell wall induced arthritis model in rats. J Rheumatol 15:1–9Google Scholar
  22. 22.
    Nakamura H, Shibakawa A, Tanaka M, Kato T, Nishioka K (2004) Effects of glucosamine hydrochloride on the production of prostaglandin E2, nitric oxide and metalloproteases by chondrocytes and synoviocytes in osteoarthritis. Clin Exp Rheumatol 22:293–299PubMedGoogle Scholar
  23. 23.
    Carbone LD, Nevitt MC, Wildy K, Barrow KD, Harris F, Felson DT, Peterfy C, Visser M, Harris TB, Benjamin BWE, Stephen B, Kritchevsky SB (2004) The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis. Arthritis Rheum 50:3516–3525PubMedCrossRefGoogle Scholar
  24. 24.
    Spector TD, Conaghan PG, Buckland-Wright JC, Garnero P, Cline GA, Valent DJ, Meyer JM (2005) Effect of risedronate on joint structure and symptoms of knee osteoarthritis: result of the BRISK randomized, controlled trial. Arthritis Res Ther 7:625–633CrossRefGoogle Scholar
  25. 25.
    Buckland-Wright JC, Messent EA, Bingham III CO, Ward RJ, Tonkin C (2007) A 2-yr longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients. Rheumatology 46:257–264PubMedCrossRefGoogle Scholar
  26. 26.
    Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, Howell D, Kaplan D, Koopman W, Longley S III, Mankin H, Mcshane DJ, Medsger T Jr, Meenan R, Mikkelsen W, Moskowitz R, Murphy W, Rothschild B, Segal M, Sokoloff L, Wolfe F (1986) Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis Rheum 29:1039–1049PubMedCrossRefGoogle Scholar
  27. 27.
    Altman R, Brandt K, Hochberg M, Moskowitz R (1996) Design and conduct of clinical trials of patients with osteoarthritis: recommendations from a task force of the Osteoarthritis Research Society. Osteoarthritis Cartilage 4:217–243PubMedCrossRefGoogle Scholar
  28. 28.
    Koshino T, Saito T, Wada J, Akamatsu Y (1997) New design of TKA; unicompartmental arthroplasty for osteoarthritis of the knee using the ceramic YMCK model. In: Niwa S, Yoshino S, Kurosawa M, Shino K, Yamamoto S (eds) Reconstruction of the Knee Joint. Springer, Berlin, pp 200–206Google Scholar
  29. 29.
    Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) 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 15:1833–1840PubMedGoogle Scholar
  30. 30.
    Ravaud P, Auleley GR, Chastang C, Rousselin B, Paolozzi L, Amor B, Dougados M (1996) Knee joint space width measurement: an experimental study of the influence of radiographic procedure and joint positioning. Br J Rheumatol 35:761–766PubMedCrossRefGoogle Scholar
  31. 31.
    Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502PubMedCrossRefGoogle Scholar
  32. 32.
    Belo JN, Berger MY, Reijman M, Koes BW, Bierma-Zeinstra SM (2007) Prognostic factors of progression of osteoarthritis of the knee: a systematic review of observational studies. Arthritis Rheum 57:13–26PubMedCrossRefGoogle Scholar
  33. 33.
    Rindone JP, Hiller D, Collacott E, Nordhargen N, Arriola G (2000) Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee. West J Med 172:91–94PubMedCrossRefGoogle Scholar
  34. 34.
    Hughes R, Carr A (2002) A randomized, double-blind, placebo-controlled trial of glucosamine sulphate as an analgesic in osteoarthritis of the knee. Rheumatology 41:279–284PubMedCrossRefGoogle Scholar
  35. 35.
    Cibere J, Kopec JA, Thorne A, Singer J, Canvin J, Robinson DB, Pope J, Hong P, Grant E, Esdaile JM (2004) Randomized, doubleblind, placebo-controlled glucosamine discontinuation trial in knee osteoarthritis. Arthritis Rheum 51:738–745PubMedCrossRefGoogle Scholar
  36. 36.
    McAlindon T, Formica M, La Valley M, Lehmer M, Kabbara K (2004) Effectiveness of glucosamine for symptoms of knee osteoarthritis: results from an Internet-based randomized double-blind controlled trial. Am J Med 117:643–649PubMedCrossRefGoogle Scholar
  37. 37.
    Clegg DO, Reda DJ, Harris CL, Klein MA, O’Dell JR, et al (2006) Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 354:795–808PubMedCrossRefGoogle Scholar
  38. 38.
    McAlindon TE, La Valley MP, Gulin JP, Felson DT (2000) Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 283:1469–1475PubMedCrossRefGoogle Scholar
  39. 39.
    Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, Wells G (2005) Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2:CD002946Google Scholar
  40. 40.
    Delmas PD (2005) The use of bisphosphonates in the treatment of osteoporosis. Curr Opin Rheumatol 17:462–466PubMedGoogle Scholar
  41. 41.
    Bingham CO III, Buckland-Wright JC, Garnero P, Cohen SB, Dougados M, Adami S, Clauw DJ, Spector TD, Pelletier JP, Raynauld JP, Strand V, Simon LS, Meyer JM, Cline GA, Beary JF (2006) Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum 54:3494–507PubMedCrossRefGoogle Scholar
  42. 42.
    Creamer P, Hochberg MC (1997) Osteoarthritis. Lancet 350:503–508PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2008

Authors and Affiliations

  • Takayuki Kawasaki
    • 1
  • Hisashi Kurosawa
    • 1
  • Hiroshi Ikeda
    • 1
  • Sung-gon Kim
    • 1
  • Aki Osawa
    • 1
  • Yuji Takazawa
    • 1
  • Mitsuaki Kubota
    • 1
  • Muneaki Ishijima
    • 1
  1. 1.Department of Orthopaedic SurgeryJuntendo University School of MedicineTokyoJapan

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