Original research| Volume 47, ISSUE 5, P377-384, September 2008

The Role of Viscosupplementation in the Ankle Using Hylan G-F 20

  • Brian Carpenter
    Residency Director, John Peter Smith Hospital, Department of Orthopaedics, Podiatry Section, Fort Worth, TX; Private Practice, North Central Texas Orthopaedics and Sports Medicine, Decatur, TX
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  • Travis Motley
    Address correspondence to: Travis Motley, DPM, MS, FACFAS, John Peter Smith Hospital, Department of Orthopaedics, Podiatry Section, 1500 South Main Street, Fort Worth, TX, 76104
    Attending Physician, Bone and Joint Research Center, Department of Orthopaedic Surgery, University of North Texas Health Science Center, Fort Worth, TX; Department of Orthopaedic Surgery, John Peter Smith Hospital (Tarrant County Hospital District), Fort Worth, TX
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      The use of intra-articular injections of high molecular weight elastoviscous solutions of hyaluronan or hylans (cross-linked derivatives of hyaluronan) to treat arthritis is termed viscosupplementation. The function of viscosupplementation is to restore the rheologic properties of synovial fluid. Although anecdotal data exist, no long-term studies regarding the use of viscosupplementation in the ankle have been published to date. The goal of this clinical trial was to compare pain reduction following ankle arthroscopy versus that following ankle arthroscopy combined with weekly intra-articular instillation of hylan G-F 20 during the first 3 postoperative weeks. In the series of patients described in this report, we found that both treatment groups experienced statistically significantly decreased pain following the intervention (P = .002 and P = .0009 for the arthroscopy alone and arthroscopy plus hylan groups, respectively), and that those who received 3 intra-articular injections of hylan G-F 20 following ankle arthroscopy improved statistically significantly (P = .0014) more than did those who underwent arthroscopy as a sole therapy. These preliminary results suggest that viscosupplementation combined with arthroscopy may be more beneficial than arthroscopy alone, and provide further insight into the role of viscosupplementation in the treatment of ankle osteoarthritis. Level of Clinical Evidence: 4

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        • Balazs E.A.
        • Denlinger J.L.
        Viscosupplementation: a new concept in the treatment of osteoarthritis.
        J Rheumatol Suppl. 1993; 39: 3-9
        • Balazs E.A.
        • Denlinger J.L.
        The synovial cell.
        in: Scarpelli D.G. Migaki G. Alan R. Modern Aging Research 4, Comparative Pathobiology of Major Age-Related Diseases Current Status and Research Frontiers. Liss, Inc, New York1984: 129-143
        • Fraser J.R.E.
        • Clarris B.J.
        • Baxter E.P.
        Patterns of induced variation in the morphology, hyaluronic acid secretion, and lysosomal enzyme activity of cultured human synovial cells.
        Ann Rheum Dis. 1979; 38: 287-294
        • Balazs E.A.
        Hyaluronic Acid and Matrix Implantation.
        Biotrix, Inc, Arlington, MA1971
        • Balazs E.A.
        • Denlinger J.L.
        Sodium hyaluronate acid and joint function.
        J Equine Vet Sci. 1985; 5: 217-218
        • Rydell N.W.
        • Butler J.
        • Balazs E.A.
        Hyaluronic acid in synovial fluid.
        Acta Vet Scand. 1970; 11: 139-155
        • Weiss C.
        • Balazs E.A.
        • St. Onge R.
        • Denlinger J.L.
        Clinical studies of the intra-articular injections of Healon (sodium hyaluronate) in the treatment of osteoarthritis of human knees.
        Semin Arthritis Rheum. 1981; 11: 143-144
        • Balazs E.A.
        The physical properties of synovial fluid and the special role of hyaluronic acid.
        in: Helfet A. Disorders of the Knee. ed 1. Lippincott, Philadelphia, PA1974: 61-74
        • Laurent T.
        • Fraser J.
        FASEB J. 1992; 6: 2397-2404
        • Darzynkiewicz Z.
        • Balazs E.A.
        Effect of connective tissue intercellular matrix on lymphocyte stimulation: I: suppression of lymphocyte stimulation by hyaluronic acid.
        Exp Cell Res. 1971; 66: 113-123
        • Forrester J.V.
        • Balazs E.A.
        Inhibition of phagocytosis by high molecular weight hyaluronan.
        Immunology. 1980; 40: 435-446
        • Forrester J.V.
        • Wilkinson P.C.
        Inhibition of leukocyte locomotion by hyaluronic acid.
        J Cell Sci. 1981; 48: 315-331
        • Smith M.M.
        • Ghosh P.
        Synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment.
        Rheumatol Int. 1987; 7: 113-122
        • Larsen N.E.
        • Lombard K.M.
        • Parent E.G.
        • Balazs E.A.
        Effect of hylan on cartilage and chondrocyte cultures.
        J Orthop Res. 1992; 10: 23-32
        • Yasui T.
        • Akatsuka M.
        • Tobetto K.
        • Hayaishi M.
        • Ando T.
        Effects of hyaluronan on the production of stromelysin and tissue inhibitior of metalloproteinase-1 in bovine articular chondrocytes.
        Biomed Res. 1992; 13: 343-348
        • Al-Assaf S.
        • Phillips G.O.
        • Deeble D.J.
        • Parsons B.
        The enhanced stability of the cross-linked hylan structure to the hydroxyl (OH) radicals compared with the uncross-linked hyaluronan.
        Radiat Phys Chem. 1995; 46: 207-217
        • Corrado E.M.
        • Peluso G.F.
        • Gigliotti S.
        • De Durante C.
        The effects of intra-articular administration of hyaluronic acid on osteoarthritis of the knee: a clinical study with immunological and biochemical evaluations.
        Eur J Rheumatol Inflamm. 1995; 15: 25-31
        • Pozo M.A.
        • Balazs E.A.
        • Belmonte C.
        Reduction of sensory responses to passive movements of inflamed knee joints by hylan, a hyaluronan derivative.
        Exp Brain Res. 1997; 116 (Erratum in: Exp Brain Res 117(3): 512, 1997): 3-9
        • Marshall K.W.
        The current status of hylan therapy for the treatment of osteoarthritis.
        Today's Therapeutic Trends. 1997; 15: 99-108
        • Ronchetti I.P.
        • Guerra D.
        • Taparelli F.
        • Boraldi F.
        • Bergamini G.
        • Mori G.
        • Zizzi F.
        • Frizziero L.
        Morphological analysis of knee synovial membrane biopsies from a randomized controlled clinical study comparing the effects of sodium hyaluronate (Hyalgan) and methylprednisolone acetate (Depomedrol) in osteoarthritis.
        J Rheumatol. 2001; 20: 158-169
        • Altman D.
        Laboratory findings in osteoarthritis.
        in: Moskowtz R. Howell D. Goldberg V. Mankin J J. Osteoarthritis—Diagnosis and Medical Surgical Management. ed 2. WB Saunders, Philadelphia, PA1992: 313-328
        • Balazs E.A.
        • Wason D.
        • Huff I.F.
        • Roseman S.
        Hyaluronic acid in synovial fluid: I.
        Arthritis Rheum. 1967; 10: 357-376
        • Balazs E.A.
        • Briller S.
        • Denlinger J.
        Na-hyaluronate molecular size variations in equine arthritis and human arthritic synovial fluid and the effect on phagocytic cells.
        in: Talbot J J. Seminars in Arthritis and Rheumatism. Grune & Stratton, New York1981: 141-143
        • Balazs E.A.
        The physical properties of synovial fluid and the special role of hyaluronic acid.
        in: Helfet A A. Disorders of the Knee. ed 2. JB Lippincott Company, Philadelphia, PA1982: 61-74
        • Dahl L.B.
        • Dahl I.M.
        • Enstron-Laurent A.
        • Granath K.
        Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies.
        Ann Rheum Dis. 1985; 44: 817-822
        • Fraser J.R.E.
        • Brown T.J.
        • Laurent T.C.
        Catabolism of hyaluronan.
        in: Laurent T.C. The Chemistry, Biology and Medical Applications of Hyaluronan and its Derivatives. Portland Press, London1998: 85-92
        • Saari H.
        • Sorsa T.
        • Kontinnen Y.T.
        Reactive oxygen species and hyaluronate in serum and synovial fluid in arthritis.
        Int J Tissue React. 1990; 12: 81-89
        • Simon L.S.
        Viscosupplementation therapy with intra-articular hyaluronic acid: fact or fantasy?.
        Osteoarthritis. 1999; 25: 345-357
        • Durr J.
        • Goodman S.
        • Potocnik A.
        • von der Mark H.
        • von der Mark K.
        Localization of B1-integrins in human cartilage and their role in chondrocyte adhesion to collagen and fibronectin.
        Exp Cell Res. 1993; 207: 235-244
        • Takigami S.
        • Takigami M.
        • Phillips G.O.
        Hydration characteristics of the cross-linked hyaluronan derivative hylan.
        Carbohydr Polym. 1993; 22: 153-160
        • Balazs E.A.
        • Denlinger J.L.
        The role of hyaluronic acid in arthritis and its therapeutic use.
        in: Peyron J.G. Osteoarthritis: Current Clinical and Fundamental Problems. Geigy, Paris1985: 165-174
        • Band P.
        • Goldman A.
        • Barbone K.
        • Reiner K.
        • Balazs E.A.
        Intra-articular distribution and residence time of hylan polymers.
        Mater Res Soc. 1995; 433 ([abstract])
        • Weiss C.
        • Band P.
        Musculoskeletal applications of hyaluronan and hylan: potential uses in the foot and ankle.
        Clin Podiatr Med Surg. 1995; 12: 497-517
        • Adams M.E.
        • Lussier A.J.
        • Peyron J.G.
        A risk-benefit assessment of injedctions of hyaluronan and its derivative in the treatment of osteoarthritis of the knee.
        Drug Saf. 2000; 2: 115-130
        • Adams M.E.
        • Atkinson M.A.
        • Lussier A.
        • 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 nonsteroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone.
        Osteoarthritis Cartilage. 1995; 3: 213-226
        • Disla E.
        • Infante R.
        • Fahmy A.
        • Karten I.
        • Cuppari G.G.
        Recurrent acute calcium pyrophosphate dihydrate arthritis following intaarticular hyaluronate injection.
        Arthritis Rheum. 1999; 42: 1302-1303
        • Lussier A.
        • Cividino A.A.
        • McFarlane C.A.
        • Olszynski W.P.
        • Potashner W.J.
        • De Medicis R.
        Viscosupplementation with hylan for the treatment of osteoarthritis: findings from clinical practice in Canada.
        J Rheumatol. 1996; 23: 1579-1585
        • Pullman-Mooar S.
        • Mooar P.
        • Sieck M.
        • Clayburne G.
        • Schumacher H.R.
        Are there distinctive inflammatory flares after hylan g-f 20 intraarticular injections?.
        J Rheumatol. 2002; 29: 2611-2614
        • Yacyshyn E.A.
        • Matteson E.L.
        Gout after intraarticular injection of hylan GF-20.
        J. Rheumatol. 1999; 26 ([letter]): 2717
        • Puttick M.P.E.
        • 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; 22: 1311-1314
        • Gray R.G.
        • Tenenbaum J.
        • Gottlieb N.L.
        Local corticosteroid injection treatment in rheumatic disorders.
        Semin Arthritis Rheum. 1981; 10: 231-254
        • Hollander J.L.
        • Jessar R.A.
        • Brown E.M.
        Intra-synovial corticosteroid therapy: a decade of use.
        Bull Rheum Dis. 1961; 9: 239-240
        • Kroesen S.
        • Schmid W.
        • Theiler R.
        Induction of an acute attack of calcium pyrophosphate dihydrate arthritis by intra-articular injection of hylan G-F 20 (Synvisc).
        Clin Rheum. 2000; 19: 147-149
        • Zardawi I.M.
        • Chan I.
        Synvisc perisynovitis.
        Pathology. 2001; 33: 519-520
        • Martens P.B.
        Bilateral symmetric inflammatory reaction to hylan G-F 20 injection.
        Arthritis Rheum. 2001; 44 ([letter]): 978-979
        • Disla E.
        • Infante R.
        • Cuppari G.G.
        Arthritis Rheum. 2000; 43 ([letter]): 1661
        • Gabriel S.E.
        • Jaakkimainen L.
        • Bombardier C.
        Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs.
        Ann Intern Med. 1991; 115: 787-796
        • Singh G.
        Recent considerations in nonsteroidal anti-inflammatory drug gastropathy.
        Am J Med. 1998; 105: 31S-38S
        • Altman R.D.
        • Moskowitz R.
        Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial.
        J Rheumatol. 1998; 25: 2203-2212
        • Sripada P.
        • Pritchard C.
        • Bankes P.F.
        Comparison of efficacy of hyaluronan and hylan G-F 20 in osteoarthritis.
        Arthritis Rheum. 1999; 42S: 296-299
        • Tobetto K.
        • Yasui T.
        • Ando T.
        • Hayaishi M.
        • Motohasi N.
        • Shinogi M.
        • Mori I.
        Inhibitory effects of hyaluronan on (14C) arachidonic acid release from labeled human synovial fibroblasts.
        Jpn J Pharmacol. 1992; 60: 79-84
        • Ghosh P.
        The role of hyaluronic acid (hyaluronan) in health and disease: interactions with cells, cartilage and components of the synovial fluid.
        Clin Exp Rheumatol. 1994; 12: 75-82
        • Presti D.
        • Scott J.E.
        Hyaluronan mediated protective effect against cell damage caused by enzymatically produced hydroxyl (OH) radicals is dependent on hyaluronan molecular mass.
        Cell Biochem Function. 1994; 12: 281-288
        • Hamerman D.
        • Wood D.D.
        Rapid communication.
        Exp Biol Med. 1984; 177: 205-210
        • Marshall K.W.
        Intra-articular hyaluronan therapy.
        Current opinion in rheumatology. 2000; 12: 468-474