Examination of synovial fluid and serum following intravenous injections of hyaluronan for the treatment of osteoarthritis in dogs

Summary

A randomized, blinded, prospective clinical trial was performed to determine the effects of intravenous (IV) administration of hyaluronan sodium (HA) on serum glycosaminoglycans (GAG) concentrations, synovial fluid (SF) hyaluronan concentrations and viscosity in dogs treated for unilateral rupture of the cranial cruciate ligament. Twenty-two dogs undergoing tibial plateau leveling osteotomy were used in this study. Synovial fluid from both stifles and serum were collected prior to surgery and at 2, 4, and 8 weeks following surgery. Dogs received either 1.0 ml (10 mg) of sodium hyaluronate (treatment group 1; n = 10) or equal volume of 0.9% NaCl (treatment group 2; n = 12), IV immediately, 2 and 4 weeks following surgery. Synovial fluid viscosity was evaluated using a magnetically driven, acoustically tracked, translating-ball rheometer. Synovial fluid HA disaccharide content was measured by fluorophore-assisted carbohydrate electrophoresis. Serum GAG concentrations were measured by alcian blue spectrophotometric assay. Data were analyzed using a Wilcoxon sign rank test (p<0.05). Mean ± SD viscosity (cP) was significantly higher (p=0.011) in SF obtained from the intact stifle (450 ± 604.1) than injured (54.8 ± 60.8) prior to surgery. Mean ± SD HA concentrations (ug/ml) were significantly higher (p=0.02) in synovial fluid obtained from the injured stifles (281.4 ± 145.9) than intact stifles (141.6 ± 132.5). No significant difference was noted within or between treatment groups in SF viscosity, HA concentrations, or serum GAG concentrations at any time following surgery. Stifles with cranial cruciate ligament insufficiency had significant alterations in SF viscosity and HA concentrations.

Keywords

Hyaluronic acid - synovial fluid - osteoarthritis

• References

• 1 Abatangelo G. et al. Intraarticular sodium hyaluronate injections in the Pond-Nuki experimental model of osteoarthritis in dogs. Biochemical results. Clin Orthop 1989; 241: 278-85.
• 2 Altman RD. et al. Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee:arandomized clinical trial. Hyalgan study group. J Rheumatol 1998; 25: 2203-12.
• 3 Arican M. et al. Hyaluronan in canine arthropathies. JComp Pathol 1994; 111: 185-95.
• 4 Balazs EA. et al. Hyaluronic acid in synovial fluid. I. Molecular parameters of hyaluronic acid in normal and arthritic human fluids. Arthritis Rheum 1967; 10: 357.
• 5 Beaty N. et al. Relative molecular weight and concentration determination of sodium hyaluronate solutions by gel-exclusion high-performance liquid chromatography. Anal Biochem 1985; 147: 387-95.
• 6 Bjornsson S. Simultaneous preparation and quantitation of proteoglycans by precipitation with alcian blue. Anal Biochem 1993; 210: 282-91.
• 7 Brown M. et al. Fluorophore-assisted carbohydrate electrophoresis (FACE) analysis of chondroitin sulphate and keratan sulphate in synovial fluid. Proceedings 49th Ann Meet Orthop Res Soc. 2003
• 8 Canapp S. et al. Serologic levels of hyaluronan, osteocalcin, and collagen 2 % in normal dogs and dogs with synovitis. Proceedings 10th AnnAm Col Vet Surg Symp 4. 2000
• 9 Dahl LB. et al. Concentration and molecular weight of sodium hyaluronic in synovial fluid from patients with rheumatoid arthritis and other arthropathies. Ann Rheum Dis 1985; 44: 817.
• 10 Dejardan LM. Tibial Plateau Leveling Procedures. Proceedings 12th Ann Am Col Vet Surg Symp 328. 2002
• 11 Frizziero L. et al. Intra-articular hyaluronic acid in the treatment of osteoarthritis of the knee: clinical and morphological study. Clin Exp Rheumatol 1998; 16: 441-9.
• 12 Gaustad G. et al. Comparison of polysulphated glycosaminoglycan and sodium hyaluronate with placebo in treatment of traumatic arthritis in horses. Equine Vet J 1995; 27: 356-62.
• 13 Gosh 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.
• 14 Gosh P. et al. The effects of intraarticular administration of hyaluronan in amodel of early osteoarthritis in sheep. Gait analysis and radiological and morphological studies. Semin Arthritis Rheum 1993; 22 (suppl) 18-30.
• 15 Hasselbacher P. Measuring synovial fluid viscosity with a white blood cell diluting pipette. Arthritis Rheum 1976; 19: 1358-62.
• 16 Hilbert BJ. et al. Hyaluronic acid concentration in synovial fluid fromnormal and arthritic joints of horses. Aust Vet J 1984; 61: 22-5.
• 17 Hilbert BJ. et al. Changes in the synovia after the intra-articular injection of sodium hyaluronate into normal horse joints and after arthrotomy and experimental cartilage damage. Aust Vet J 1985; 62: 182-4.
• 18 Hollander JL. et al. Examination of synovial fluid as a diagnostic aid in arthritis. Med Clin North Am 1966; 50: 1281-39.
• 19 Howard RD. et al. Hyaluronan and its use in the treatment of equine joint disease. In: Mcllwraith WC, Trotter GW. Joint Disease in the Horse. W.B. Saunders Company; 1996: 257-69.
• 20 Huskisson EC. et al. Hyaluronic acid in the treatment of osteoarthritis of the knee. J Rheumatol 1999; 38: 602-7.
• 21 Iwata H. Pharmacologic and clinical aspects of intraarticular injection of hyaluronate. Clin Orthop 1993; 289-5.
• 22 Kawasaki K. et al. Hyaluronic acid enhances proliferation and chondroitin sulphate synthesis in cultured chondrocyte embedded in collagen gels. J Cell Physiol 1999; 179: 142-8.
• 23 Kawcak CE. et al. Effect of intravenous administration of sodium hyaluronate on carpal joints in exercising horses after arthroscopic surgery and osteochondral fragmentation. Am J Vet Res 1997; 58: 1132-40.
• 24 Kobayashi K. The long term effects of hyaluronan during development of osteoarthritis following partial menisectomy in a rabbit model. Osteoarthritis Cartilage 2000; 8: 359-65.
• 25 Kongtawelert P. et al. An enzyme-linked immunosorbent-inhibition assay for quantitation of hyaluronan (Hyaluronic acid) in biological fluids. Anal Bioch 1989; 178: 367-72.
• 26 Kuroki K. et al. Mechanisms of action and potential uses of hyaluronan in dogs with osteoarthritis. J Am Vet Med Assoc 2002; 221: 944-50.
• 27 Larkin J. et al. The correlation of clinical assessment of synovial fluid with its measured viscosity. Br J Rheumatol 1984; 23: 195-7.
• 28 Larsen NE. et al. Effect of hylan on cartilage and chondrocyte cultures. J Orthop Res 1992; 10: 23-32.
• 29 Lussier A. et al. Viscosupplementation with hylan for the treatment of osteoarthitis: findings from clinical practice in Can. J Rheumatol 1996; 23: 1579-85.
• 30 Marshall KW. et al. Amelioration of disease severity by intraarticular Hylan therapy in bilateral canine osteoarthritis. J Orthop Res 2000; 18: 416-25.
• 31 Mcllwraith CW. Diseases of joints, tendons, ligaments and related structures. In: Stashak TS. ed Adams' Lameness in Horses. Philadelphia, Pa: Lea & Febiger; 1984: 368-9.
• 32 Mensitieri M. et al. Viscoelastic evaluation of different knee osteoarthritis therapies. J Rheumatol 1995; 130-7.
• 33 Morris EA. et al. Inhibition of interleukin 1mediated proteoglycan degradation in bovine articular cartilage explants by addition of sodium hyaluronate. Am J Vet Res 1992; 53: 1977-82.
• 34 Calabro A. et al. Fluorophore-assisted carbohydrate electrophoresis (FACE) of glycosaminoglycans. Osteoarthritis Cartilage 2001; 9 Suppl A S16-22.
• 35 Peyron J. Intraarticular hyaluronan injections in the treatment of osteoarthritis: state-of-the-art review. J Rheumatol 1993; 20 (suppl 39) 10-5.
• 36 Presti D. et al. Hyaluronan mediated protective effect against cell damage caused by enzymatically generated hydroxyl radicals is dependent on hyaluronan molecular mass. Cell Biochem Funct 1994; 12: 281-8.
• 37 Ropes MW. et al. Diagnostic criteria for rheumatoid arthritis-1958 revision. Ann Rheum Dis 1959; 18: 49-53.
• 38 Sakakibara Y. et al. Effect of high-molecular weight sodium hyaluronate on immobilized rabbit knee. Clin Orthop 1994; 229: 282-92.
• 39 Schiavinato A. et al. Intraarticular sodium hyaluronate injections in the Pond-Nuki experimental model of osteoarthritis on dogs. Morphological findings. Clin Orthop 1989; 241: 286-99.
• 40 Sharif M. et al. Serum hyaluronic acid level as a predictor of disease progression in osteoarthritis of the knee. Arthritis Rheum 1995; 38: 760-7.
• 41 Shimazu A. et al. Effects of hyaluronic acid on the release of proteoglycan from cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines. Arthritis Rheum 1993; 36: 247-53.
• 42 Smith GN. et al. Effect of intraarticular HA injection on the synovial fluid of OA joints. Proceedings 46th Ann Meet Orthop Res Soc. 2000: 233.
• 43 Smith GN. et al. Effect of intraarticular hyaluronan injection on synovial fluid hyaluronan in the early stage of canine post-traumatic osteoarthritis. J Rheumatol 2001; 28: 1341-6.
• 44 Smith GN. et al. Effectof intra-articular hyaluronan injection in experimental canine osteoarthritis. Arthritis Rheum 1998; 41: 976-85.
• 45 Takahashi K. et al. The effects of hyaluronan on matrix metalloproteinase 3 (MMP3), interlukin 1 beta (IL1 beta), and tissue inhibitor of metalloproteinase 1 (TIMP1) gene expression during the development of osteoarthritis. Osteoarthritis Cartilage 1999; 7: 182-90.
• 46 Tran-Son-Tay R. et al. Magnetically driven, acoustically tracked, translating-ball rheometer for small, opaque samples. Rev Sci Instrum 1988; 59: 1399-405.
• 47 Tulamo RM. et al. Concentration and molecular weight distribution of hyaluronate in synovial fluid from clinically normal horses and horses with diseased joints. Am J Vet Res 1994; 55: 710-5.
• 48 Tulamo RM. et al. Hyaluronate and large molecular weight proteoglycans in synovial fluid from horses with various arthritides. Am J Vet Res 1996; 57: 932-7.
• 49 Uebelhart D. et al. Effects of hyaluronic acid on cartilage degradation. Curr Opin Rheumatol 1999; 11: 427-35.
• 50 Yasui T. et al. The effect ofhyaluronan on interlukin 1 induced prostaglandin E-2 production in human osteoarthritis synovial cells. Agents Actions 1992; 37: 156-6.