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. 2003 Aug;79(934):449–453. doi: 10.1136/pmj.79.934.449

Intra-articular therapy in osteoarthritis

I Uthman 1, J Raynauld 1, B Haraoui 1
PMCID: PMC1742771  PMID: 12954956

Abstract

The medical literature was reviewed from 1968–2002 using Medline and the key words "intra-articular" and "osteoarthritis" to determine the various intra-articular therapies used in the treatment of osteoarthritis. Corticosteroids and hyaluronic acid are the most frequently used intra-articular therapies in osteoarthritis. Other intra-articular substances such as orgotein, radiation synovectomy, dextrose prolotherapy, silicone, saline lavage, saline injection without lavage, analgesic agents, non-steroidal anti-inflammatory drugs, glucosamine, somatostatin, sodium pentosan polysulfate, chloroquine, mucopolysaccharide polysulfuric acid ester, lactic acid solution, and thiotepa cytostatica have been investigated as potentially therapeutic in the treatment of arthritic joints. Despite the lack of strong, convincing, and reproducible evidence that any of the intra-articular therapies significantly alters the progression of osteoarthritis, corticosteroids and hyaluronic acid are widely used in patients who have failed other therapeutic modalities for lack of efficacy or toxicity. As a practical approach for a knee with effusion, steroid injections should be considered while the presence of symptomatic "dry" knees may favour the hyaluronic acid approach. The virtual absence of serious side effects, coupled with the perceived benefits, make these approaches attractive.

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Selected References

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  1. Adams M. E., Atkinson M. H., Lussier A. J., Schulz J. I., Siminovitch K. A., Wade J. P., Zummer M. The role of viscosupplementation with hylan G-F 20 (Synvisc) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone. Osteoarthritis Cartilage. 1995 Dec;3(4):213–225. doi: 10.1016/s1063-4584(05)80013-5. [DOI] [PubMed] [Google Scholar]
  2. Altman R. D. Intra-articular sodium hyaluronate in osteoarthritis of the knee. Semin Arthritis Rheum. 2000 Oct;30(2 Suppl 1):11–18. doi: 10.1053/sarh.2000.0248. [DOI] [PubMed] [Google Scholar]
  3. Altman R. D., Moskowitz R. Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. Hyalgan Study Group. J Rheumatol. 1998 Nov;25(11):2203–2212. [PubMed] [Google Scholar]
  4. Balazs E. A., Denlinger J. L. Viscosupplementation: a new concept in the treatment of osteoarthritis. J Rheumatol Suppl. 1993 Aug;39:3–9. [PubMed] [Google Scholar]
  5. Balch H. W., Gibson J. M., El-Ghobarey A. F., Bain L. S., Lynch M. P. Repeated corticosteroid injections into knee joints. Rheumatol Rehabil. 1977 Aug;16(3):137–140. doi: 10.1093/rheumatology/16.3.137. [DOI] [PubMed] [Google Scholar]
  6. Brandt K. D., Block J. A., Michalski J. P., Moreland L. W., Caldwell J. R., Lavin P. T. Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group. Clin Orthop Relat Res. 2001 Apr;(385):130–143. doi: 10.1097/00003086-200104000-00021. [DOI] [PubMed] [Google Scholar]
  7. Brandt K. D., Smith G. N., Jr, Simon L. S. Intraarticular injection of hyaluronan as treatment for knee osteoarthritis: what is the evidence? Arthritis Rheum. 2000 Jun;43(6):1192–1203. doi: 10.1002/1529-0131(200006)43:6<1192::AID-ANR2>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  8. Brocq Olivier, Tran Gali, Breuil Véronique, Grisot Christian, Flory Philippe, Euller-Ziegler Liana. Hip osteoarthritis: short-term efficacy and safety of viscosupplementation by hylan G-F 20. An open-label study in 22 patients. Joint Bone Spine. 2002 Jun;69(4):388–391. doi: 10.1016/s1297-319x(02)00416-5. [DOI] [PubMed] [Google Scholar]
  9. Cederlöf S., Jonson G. Intraarticular prednisolone injection for osteoarthritis of the knee. A double blind test with placebo. Acta Chir Scand. 1966 Nov;132(5):532–537. [PubMed] [Google Scholar]
  10. Corbett M., Seifert M. H., Hacking C., Webb S. Comparison between local injections of silicone oil and hydrocortisone acetate in chronic arthritis. Br Med J. 1970 Jan 3;1(5687):24–25. doi: 10.1136/bmj.1.5687.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Creamer P., Hunt M., Dieppe P. Pain mechanisms in osteoarthritis of the knee: effect of intraarticular anesthetic. J Rheumatol. 1996 Jun;23(6):1031–1036. [PubMed] [Google Scholar]
  12. Dahlberg L., Lohmander L. S., Ryd L. Intraarticular injections of hyaluronan in patients with cartilage abnormalities and knee pain. A one-year double-blind, placebo-controlled study. Arthritis Rheum. 1994 Apr;37(4):521–528. doi: 10.1002/art.1780370412. [DOI] [PubMed] [Google Scholar]
  13. Dawes P. T., Kirlew C., Haslock I. Saline washout for knee osteoarthritis: results of a controlled study. Clin Rheumatol. 1987 Mar;6(1):61–63. doi: 10.1007/BF02201002. [DOI] [PubMed] [Google Scholar]
  14. Dieppe P. A., Sathapatayavongs B., Jones H. E., Bacon P. A., Ring E. F. Intra-articular steroids in osteoarthritis. Rheumatol Rehabil. 1980 Nov;19(4):212–217. doi: 10.1093/rheumatology/19.4.212. [DOI] [PubMed] [Google Scholar]
  15. Dixon A. S., Jacoby R. K., Berry H., Hamilton E. B. Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee. Curr Med Res Opin. 1988;11(4):205–213. doi: 10.1185/03007998809114237. [DOI] [PubMed] [Google Scholar]
  16. Dougados M., Nguyen M., Listrat V., Amor B. High molecular weight sodium hyaluronate (hyalectin) in osteoarthritis of the knee: a 1 year placebo-controlled trial. Osteoarthritis Cartilage. 1993 Apr;1(2):97–103. doi: 10.1016/s1063-4584(05)80024-x. [DOI] [PubMed] [Google Scholar]
  17. Dougados M. Sodium hyaluronate therapy in osteoarthritis: arguments for a potential beneficial structural effect. Semin Arthritis Rheum. 2000 Oct;30(2 Suppl 1):19–25. doi: 10.1053/sarh.2000.0246. [DOI] [PubMed] [Google Scholar]
  18. Edelson R., Burks R. T., Bloebaum R. D. Short-term effects of knee washout for osteoarthritis. Am J Sports Med. 1995 May-Jun;23(3):345–349. doi: 10.1177/036354659502300317. [DOI] [PubMed] [Google Scholar]
  19. Edmonds J., Smart R., Laurent R., Butler P., Brooks P., Hoschl R., Wiseman J., George S., Lovegrove F., Warwick A. A comparative study of the safety and efficacy of dysprosium-165 hydroxide macro-aggregate and yttrium-90 silicate colloid in radiation synovectomy--a multicentre double blind clinical trial. Australian Dysprosium Trial Group. Br J Rheumatol. 1994 Oct;33(10):947–953. doi: 10.1093/rheumatology/33.10.947. [DOI] [PubMed] [Google Scholar]
  20. Egsmose C., Lund B., Bach Andersen R. Hip joint distension in osteoarthrosis. A triple-blind controlled study comparing the effect of intra-articular indoprofen with placebo. Scand J Rheumatol. 1984;13(3):238–242. doi: 10.3109/03009748409100392. [DOI] [PubMed] [Google Scholar]
  21. Friedman D. M., Moore M. E. The efficacy of intraarticular steroids in osteoarthritis: a double-blind study. J Rheumatol. 1980 Nov-Dec;7(6):850–856. [PubMed] [Google Scholar]
  22. Gaffney K., Ledingham J., Perry J. D. Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response. Ann Rheum Dis. 1995 May;54(5):379–381. doi: 10.1136/ard.54.5.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gammer W., Brobäck L. G. Clinical comparison of orgotein and methylprednisolone acetate in the treatment of osteoarthrosis of the knee joint. Scand J Rheumatol. 1984;13(2):108–112. doi: 10.3109/03009748409100372. [DOI] [PubMed] [Google Scholar]
  24. Grecomoro G., Martorana U., Di Marco C. Intra-articular treatment with sodium hyaluronate in gonarthrosis: a controlled clinical trial versus placebo. Pharmatherapeutica. 1987;5(2):137–141. [PubMed] [Google Scholar]
  25. Grecomoro G., Piccione F., Letizia G. Therapeutic synergism between hyaluronic acid and dexamethasone in the intra-articular treatment of osteoarthritis of the knee: a preliminary open study. Curr Med Res Opin. 1992;13(1):49–55. doi: 10.1185/03007999209115222. [DOI] [PubMed] [Google Scholar]
  26. Gristina A. G., Pace N. A., Kantor T. G., Thompson W. A. Intra-articular thio-tepa compared with depomedrol and procaine in the treatment of arthritis. J Bone Joint Surg Am. 1970 Dec;52(8):1603–1610. [PubMed] [Google Scholar]
  27. Guidolin D. D., Ronchetti I. P., Lini E., Guerra D., Frizziero L. Morphological analysis of articular cartilage biopsies from a randomized, clinical study comparing the effects of 500-730 kDa sodium hyaluronate (Hyalgan) and methylprednisolone acetate on primary osteoarthritis of the knee. Osteoarthritis Cartilage. 2001 May;9(4):371–381. doi: 10.1053/joca.2000.0398. [DOI] [PubMed] [Google Scholar]
  28. Helal B., Karadi B. S. Artificial lubrication of joints: use of silicone oil. Ann Phys Med. 1968 Nov;9(8):334–340. doi: 10.1093/rheumatology/9.8.334. [DOI] [PubMed] [Google Scholar]
  29. Henderson E. B., Smith E. C., Pegley F., Blake D. R. Intra-articular injections of 750 kD hyaluronan in the treatment of osteoarthritis: a randomised single centre double-blind placebo-controlled trial of 91 patients demonstrating lack of efficacy. Ann Rheum Dis. 1994 Aug;53(8):529–534. doi: 10.1136/ard.53.8.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hochberg M. C., Perlmutter D. L., Hudson J. I., Altman R. D. Preferences in the management of osteoarthritis of the hip and knee: results of a survey of community-based rheumatologists in the United States. Arthritis Care Res. 1996 Jun;9(3):170–176. doi: 10.1002/1529-0131(199606)9:3<170::aid-anr1790090304>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  31. Huskisson E. C., Scott J. Orgotein in osteoarthritis of the knee joint. Eur J Rheumatol Inflamm. 1981;4(2):212–218. [PubMed] [Google Scholar]
  32. Ike R. W., Arnold W. J., Rothschild E. W., Shaw H. L. Tidal irrigation versus conservative medical management in patients with osteoarthritis of the knee: a prospective randomized study. Tidal Irrigation Cooperating Group. J Rheumatol. 1992 May;19(5):772–779. [PubMed] [Google Scholar]
  33. Jones A., Doherty M. Intra-articular corticosteroids are effective in osteoarthritis but there are no clinical predictors of response. Ann Rheum Dis. 1996 Nov;55(11):829–832. doi: 10.1136/ard.55.11.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Keagy R. D., Keim H. A. Intra-articular steroid therapy: repeated use in patients with chronic arthritis. Am J Med Sci. 1967 Jan;253(1):45–51. [PubMed] [Google Scholar]
  35. Kumar M., Dikshit O. P. Intra-articular lactic acid solution in osteoarthritis. J Indian Med Assoc. 1968 May 1;50(9):420–422. [PubMed] [Google Scholar]
  36. Langkilde M., Rossel I. Intra-articular use of cytostatica. (Thio-Tepa, Azetepa and Osmium acid). Acta Rheumatol Scand. 1967;13(2):92–100. doi: 10.3109/rhe1.1967.13.issue-1-4.09. [DOI] [PubMed] [Google Scholar]
  37. Leardini G., Mattara L., Franceschini M., Perbellini A. Intra-articular treatment of knee osteoarthritis. A comparative study between hyaluronic acid and 6-methyl prednisolone acetate. Clin Exp Rheumatol. 1991 Jul-Aug;9(4):375–381. [PubMed] [Google Scholar]
  38. Likar R., Schäfer M., Paulak F., Sittl R., Pipam W., Schalk H., Geissler D., Bernatzky G. Intraarticular morphine analgesia in chronic pain patients with osteoarthritis. Anesth Analg. 1997 Jun;84(6):1313–1317. doi: 10.1097/00000539-199706000-00025. [DOI] [PubMed] [Google Scholar]
  39. Listrat V., Ayral X., Patarnello F., Bonvarlet J. P., Simonnet J., Amor B., Dougados M. Arthroscopic evaluation of potential structure modifying activity of hyaluronan (Hyalgan) in osteoarthritis of the knee. Osteoarthritis Cartilage. 1997 May;5(3):153–160. doi: 10.1016/s1063-4584(97)80010-6. [DOI] [PubMed] [Google Scholar]
  40. Lohmander L. S., Dalén N., Englund G., Hämäläinen M., Jensen E. M., Karlsson K., Odensten M., Ryd L., Sernbo I., Suomalainen O. Intra-articular hyaluronan injections in the treatment of osteoarthritis of the knee: a randomised, double blind, placebo controlled multicentre trial. Hyaluronan Multicentre Trial Group. Ann Rheum Dis. 1996 Jul;55(7):424–431. doi: 10.1136/ard.55.7.424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lussier A., Cividino A. A., McFarlane C. A., Olszynski W. P., Potashner W. J., De Médicis R. Viscosupplementation with hylan for the treatment of osteoarthritis: findings from clinical practice in Canada. J Rheumatol. 1996 Sep;23(9):1579–1585. [PubMed] [Google Scholar]
  42. Luzar M. J., Altawil B. Pseudogout following intraarticular injection of sodium hyaluronate. Arthritis Rheum. 1998 May;41(5):939–940. doi: 10.1002/1529-0131(199805)41:5<939::AID-ART24>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  43. Maillefert J. F., Hirschhorn P., Pascaud F., Piroth C., Tavernier C. Acute attack of chondrocalcinosis after an intraarticular injection of hyaluronan. Rev Rhum Engl Ed. 1997 Oct;64(10):593–594. [PubMed] [Google Scholar]
  44. Mandell B. F., Lipani J. Refractory osteoarthritis. Differential diagnosis and therapy. Rheum Dis Clin North Am. 1995 Feb;21(1):163–178. [PubMed] [Google Scholar]
  45. Mazières B., Masquelier A. M., Capron M. H. A French controlled multicenter study of intraarticular orgotein versus intraarticular corticosteroids in the treatment of knee osteoarthritis: a one-year followup. J Rheumatol Suppl. 1991 Feb;27:134–137. [PubMed] [Google Scholar]
  46. Menkes C. J. Intraarticular treatment of osteoarthritis and guidelines to its assessment. J Rheumatol Suppl. 1994 Sep;41:74–76. [PubMed] [Google Scholar]
  47. Miltner O., Schneider U., Siebert C. H., Niedhart C., Niethard F. Uwe. Efficacy of intraarticular hyaluronic acid in patients with osteoarthritis--a prospective clinical trial. Osteoarthritis Cartilage. 2002 Sep;10(9):680–686. doi: 10.1053/joca.2002.0815. [DOI] [PubMed] [Google Scholar]
  48. Moens B., Moens C. H. Intra-articular injection of phenylbutazone in gonarthrosis. Ann Rheum Dis. 1986 Sep;45(9):788–788. doi: 10.1136/ard.45.9.788-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Namiki O., Toyoshima H., Morisaki N. Therapeutic effect of intra-articular injection of high molecular weight hyaluronic acid on osteoarthritis of the knee. Int J Clin Pharmacol Ther Toxicol. 1982 Nov;20(11):501–507. [PubMed] [Google Scholar]
  50. Papathanassiou N. P. Intra-articular use of tenoxicam in degenerative osteoarthritis of the knee joint. J Int Med Res. 1994 Nov-Dec;22(6):332–337. doi: 10.1177/030006059402200604. [DOI] [PubMed] [Google Scholar]
  51. Pelletier J. P., Cloutier J. M., Martel-Pelletier J. In vitro effects of NSAIDs and corticosteroids on the synthesis and secretion of interleukin 1 by human osteoarthritic synovial membranes. Agents Actions Suppl. 1993;39:181–193. doi: 10.1007/978-3-0348-7442-7_21. [DOI] [PubMed] [Google Scholar]
  52. Pelletier J. P., Martel-Pelletier J. Protective effects of corticosteroids on cartilage lesions and osteophyte formation in the Pond-Nuki dog model of osteoarthritis. Arthritis Rheum. 1989 Feb;32(2):181–193. doi: 10.1002/anr.1780320211. [DOI] [PubMed] [Google Scholar]
  53. Pelletier J. P., Mineau F., Raynauld J. P., Woessner J. F., Jr, Gunja-Smith Z., Martel-Pelletier J. Intraarticular injections with methylprednisolone acetate reduce osteoarthritic lesions in parallel with chondrocyte stromelysin synthesis in experimental osteoarthritis. Arthritis Rheum. 1994 Mar;37(3):414–423. doi: 10.1002/art.1780370316. [DOI] [PubMed] [Google Scholar]
  54. Puttick M. P., Wade J. P., Chalmers A., Connell D. G., Rangno K. K. Acute local reactions after intraarticular hylan for osteoarthritis of the knee. J Rheumatol. 1995 Jul;22(7):1311–1314. [PubMed] [Google Scholar]
  55. Ravaud P., Moulinier L., Giraudeau B., Ayral X., Guerin C., Noel E., Thomas P., Fautrel B., Mazieres B., Dougados M. Effects of joint lavage and steroid injection in patients with osteoarthritis of the knee: results of a multicenter, randomized, controlled trial. Arthritis Rheum. 1999 Mar;42(3):475–482. doi: 10.1002/1529-0131(199904)42:3<475::AID-ANR12>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  56. Raynauld J. P. Clinical trials: impact of intraarticular steroid injections on the progression of knee osteoarthritis. Osteoarthritis Cartilage. 1999 May;7(3):348–349. doi: 10.1053/joca.1998.0193. [DOI] [PubMed] [Google Scholar]
  57. Raynauld Jean-Pierre, Buckland-Wright Chris, Ward Rupert, Choquette Denis, Haraoui Boulos, Martel-Pelletier Johanne, Uthman Imad, Khy Visithan, Tremblay Jean-Luc, Bertrand Carole. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2003 Feb;48(2):370–377. doi: 10.1002/art.10777. [DOI] [PubMed] [Google Scholar]
  58. Reeves K. D., Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000 Mar;6(2):68-74, 77-80. [PubMed] [Google Scholar]
  59. Sambrook P. N., Champion G. D., Browne C. D., Cairns D., Cohen M. L., Day R. O., Graham S., Handel M., Jaworski R., Kempler S. Corticosteroid injection for osteoarthritis of the knee: peripatellar compared to intra-articular route. Clin Exp Rheumatol. 1989 Nov-Dec;7(6):609–613. [PubMed] [Google Scholar]
  60. Silveri F., Morosini P., Brecciaroli D., Cervini C. Intra-articular injection of somatostatin in knee osteoarthritis: clinical results and IGF-1 serum levels. Int J Clin Pharmacol Res. 1994;14(2):79–85. [PubMed] [Google Scholar]
  61. Stein A., Yassouridis A., Szopko C., Helmke K., Stein C. Intraarticular morphine versus dexamethasone in chronic arthritis. Pain. 1999 Dec;83(3):525–532. doi: 10.1016/S0304-3959(99)00156-6. [DOI] [PubMed] [Google Scholar]
  62. Tanaka S., Ito T. Intraarticular injection of mucopolysaccharide polysulfuric acid ester in the treatment of osteoarthritis of the hip joints. Nihon Geka Hokan. 1976 Jul 1;45(4):289–297. [PubMed] [Google Scholar]
  63. Tejeswar Rao P. Intra-articular chloroquine in rheumatoid and osteo-arthritis of knee joint. J Indian Med Assoc. 1977 Nov 1;69(9):193–195. [PubMed] [Google Scholar]
  64. Towheed T. E., Hochberg M. C. A systematic review of randomized controlled trials of pharmacological therapy in osteoarthritis of the knee, with an emphasis on trial methodology. Semin Arthritis Rheum. 1997 Apr;26(5):755–770. doi: 10.1016/s0049-0172(97)80043-1. [DOI] [PubMed] [Google Scholar]
  65. Vajaradul Y. Double-blind clinical evaluation of intra-articular glucosamine in outpatients with gonarthrosis. Clin Ther. 1981;3(5):336–343. [PubMed] [Google Scholar]
  66. Valtonen E. J. Clinical comparison of triamcinolonehexacetonide and betamethasone in the treatment of osteoarthrosis of the knee-joint. Scand J Rheumatol Suppl. 1981;41:1–7. [PubMed] [Google Scholar]
  67. Will R., Laing B., Edelman J., Lovegrove F., Surveyor I. Comparison of two yttrium-90 regimens in inflammatory and osteoarthropathies. Ann Rheum Dis. 1992 Feb;51(2):262–265. doi: 10.1136/ard.51.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wright V., Haslock D. I., Dowson D., Seller P. C., Reeves B. Evaluation of silicone as an artificial lubricant in osteoarthrotic joints. Br Med J. 1971 May 15;2(5758):370–373. doi: 10.1136/bmj.2.5758.370. [DOI] [PMC free article] [PubMed] [Google Scholar]

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