Abstract
Background
Intra-articular injections of sodium hyaluronate (Na-HA) and corticosteroid (CS) are often used for the treatment of osteoarthritis (OA), and the clinical usefulness of such treatment has been reported. Some studies have discussed the effectiveness of intra-articular drug injection therapy in terms of the clinical results, but no cohort studies have performed evaluations of effectiveness based on changes in joint biomarkers. This prospective randomized study compared the efficacy of Na-HA and CS injections based on clinical scores and levels of biochemical markers for osteoarthritis.
Methods
A total of 51 patients with knee osteoarthritis received intra-articular injections of either Na-HA or CS and were followed for 6 months after treatment. Pain and inflammatory scores were evaluated at the baseline, at 5 weeks, and at 6 months. We also measured joint fluid levels of hyaluronan (HA), chondroitin 6-sulfate, chondroitin 4-sulfate, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP (TIMP)-1 at the baseline and at 5 weeks.
Results
In both groups, injection therapy significantly improved pain/inflammation scores and visual analog scale scores with time (P < 0.01). HA levels were significantly increased after injection only in the Na-HA group (P < 0.05); and the MMP-9 level decreased significantly after injection only in the Na-HA group (P < 0.01). Other marker levels did not differ significantly between groups.
Conclusions
The results of this prospective randomized study suggest that the clinical effects of Na-HA and CS as local therapies for OA are comparable and that both drugs are useful. Considering the results of the measurement of biomarkers, compared with CS injection therapy Na-HA injection therapy may have protective effects on the articular cartilage by increasing the HA concentration in synovial fluid, as well as inhibitory effects on the catabolism of articular cartilage by reducing the MMP-9 concentration.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Poole AR, Rizkalla G, Ionescu M, Reiner A, Brooks E, Rorabeck C, et al. Osteoarthritis in the human knee: a dynamic process of cartilage matrix degradation, synthesis and reorganization. Agents Actions Suppl 1993;39:3–13.
Buckwalter JA, Stanish WD, Rosier RN, Schenck RC Jr, Dennis DA, Coutts RD. The increasing need for nonoperative treatment of patients with osteoarthritis. Clin Orthop 2001;385:36–45.
Day R, Brooks P, Conaghan PG, Petersen M. A double blind, randomized, multicenter, parallel group study of the effectiveness and tolerance of intraarticular hyaluronan in osteoarthritis of the knee. J Rheumatol 2004;31:775–782.
Shimazu A, Jikko A, Iwamoto M, Koike T, Yan W, Okada Y, et al. Effects of hyaluronic acid on the release of proteoglycan from the cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines. Arthritis Rheum 1993;36:247–253.
Gotoh S, Onaya J, Abe M, Miyazaki K, Hamai A, Horie K, et al. Effects of the molecular weight of hyaluronic acid and its action mechanisms on experimental joint pain in rats. Ann Rheum Dis 1993;52:817–822.
Asari A, Miyauchi S, Matsuzaka S, Ito T, Kominami E, Uchiyama Y. Molecular weight-dependent effects of hyaluronate on the arthritic synovium. Arch Histol Cytol 1998;61:125–135.
Creamer P. Intra-articular corticosteroid treatment in osteoarthritis. Curr Opin Rheumatol 1999;11:417–421.
Leopold SS, Redd BB, Warme WJ, Wehrle PA, Pettis PD, Shott S. Corticosteroid compared with hyaluronic acid injections for the treatment of osteoarthritis of the knee: a prospective, randomized trial. J Bone Joint Surg Am 2003;85:1197–1203.
Jones AC, Patrick M, Doherty S, Doherty M. Intra-articular hyaluronic acid compared to intra-articular triamcinolone hexacetonide in inflammatory knee osteoarthritis. Osteoarthritis Cartilage 1995;3:269–273.
Caborn D, Rush J, Lanzer W, Parenti D, Murray C; Synvisc 901 Study Group. A randomized, single-blind comparison of the efficacy and tolerability of hylan G-F 20 and triamcinolone hexacetonide in patients with osteoarthritis of the knee. J Rheumatol 2004;31:333–343.
Witter J, Roughley PJ, Webber C, Roberts N, Keystone E, Poole AR. The immunologic detection and characterization of cartilage proteoglycan degradation products in synovial fluids of patients with arthritis. Arthritis Rheum 1987;30:519–529.
Lohmander LS, Neame PJ, Sandy JD. The structure of aggrecan fragments in human synovial fluid: evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury, and osteoarthritis. Arthritis Rheum 1993;36:1214–1222.
Okada Y, Gonoji Y, Naka K, Tomita K, Nakanishi I, Iwata K, et al. Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells: purification and activation of the precursor and enzymic properties. J Biol Chem 1992;267:21712–21719.
Kanyama M, Kuboki T, Kojima S, Fujisawa T, Hattori T, Takigawa M, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids of patients with temporomandibular joint osteoarthritis. J Orofac Pain 2000;14:20–30.
Smith MD, Wetherall M, Darby T, Esterman A, Slavotinek J, Roberts-Thomson P, et al. A randomized placebo-controlled trial of arthroscopic lavage versus lavage plus intra-articular corticosteroids in the management of symptomatic osteoarthritis of the knee. Rheumatology 2003;42:1477–1485.
Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis 1957;16:494–502.
Gotoh M, Hanyu T, Yoshio T, Matsuno H, Shimizu M, Murata N, et al. Intra-articular injection of hyaluronate (SI-6601D) improves joint pain and synovial fluid prostaglandin E2 levels in rheumatoid arthritis: a multicenter clinical trial. Clin Exp Rheumatol 2001;19:377–383.
Reissig JL, Storminger JL, Leloir LF. A modified colorimetric method for the estimation of N-acetylamino sugars. J Biol Chem 1955;217:959–966.
Shinmei M, Miyauchi S, Machida A, Miyazaki K. Quantitation of chondroitin 4-sulfate and chondroitin 6-sulfate in pathologic joint fluid. Arthritis Rheum 1992;35:1304–1308.
Fujimoto N, Hosokawa N, Iwata K, Shinya T, Okada Y, Hayakawa T. A one-step sandwich enzyme immunoassay for inactive precursor and complexed forms of human matrix metalloproteinase 9 (92 kDa gelatinase/type IV collagenase, gelatinase B) using monoclonal antibodies. Clin Chim Acta 1994;231:79–88.
Kodama S, Kishi J, Obata K, Iwata K, Hayakawa T. Monoclonal antibodies to bovine collagenase inhibitor. Coll Relat Res 1987;7:341–350.
Pelletier JP, Cloutier JM, Martel-Pelletier J. In vitro effects of tiaprofenic acid, sodium salicylate and hydrocortisone on the proteoglycan metabolism of human osteoarthritic cartilage. J Rheumatol 1989;16:646–655.
Hasegawa M, Nakoshi Y, Tsujii M, Sudo A, Masuda H, Yoshida T, et al. Changes in biochemical markers and prediction of effectiveness of intra-articular hyaluronan in patients with knee osteoarthritis. Osteoarthritis Cartilage 2008;16:526–529.
Iwata H. Pharmacologic and clinical aspects of intraarticular injection of hyaluronate. Clin Orthop 1993;289:285–291.
Tchetverikov I, Ronday HK, Van El B, Kiers GH, Verzijl N, TeKoppele JM, et al. MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis. Ann Rheum Dis 2004;63:881–883.
Fraser A, Fearon U, Reece R, Emery P, Veale DJ. Matrix metalloproteinase 9, apoptosis, and vascular morphology in early arthritis. Arthritis Rheum 2001;44:2024–2028.
Hsieh YS, Yang SF, Lue KH, Chu SC, Lu KH. Effects of different molecular weight hyaluronan products on the expression of urokinase plasminogen activator and inhibitor and gelatinases during the early stage of osteoarthritis. J Orthop Res 2008;26:475–484.
Author information
Authors and Affiliations
About this article
Cite this article
Shimizu, M., Higuchi, H., Takagishi, K. et al. Clinical and biochemical characteristics after intra-articular injection for the treatment of osteoarthritis of the knee: prospective randomized study of sodium hyaluronate and corticosteroid. J Orthop Sci 15, 51–56 (2010). https://doi.org/10.1007/s00776-009-1421-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00776-009-1421-0