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BMC veterinary research2016; 12; 60; doi: 10.1186/s12917-016-0687-7

A randomised, double-blinded, placebo-controlled clinical study on intra-articular hyaluronan treatment in equine lameness originating from the metacarpophalangeal joint.

Abstract: Intra-articular inflammation resulting in lameness is a common health problem in horses. Exogenous intra-articular hyaluronic acid has been shown to provide an analgesic effect and reduce pain in equine and human osteoarthritis. High molecular weight non-animal stabilized hyaluronic acid (NASHA) has gained popularity in the treatment of human arthritic conditions due to its long-acting pain-relieving effects. The aim of this study was to compare the response to treatment of lameness localized in the equine metacarpophalangeal joint injected with non-animal stabilized hyaluronic acid (NASHA) and placebo (saline). Twenty-seven clinically lame horses with a positive response to diagnostic intra-articular anaesthesia of the metacarpophalangeal joint and with no, or at most mild, radiographic changes in this joint were included in the study. Horses in the treatment group (n = 14) received 3 mL of a NASHA product intra-articularly, and those in the placebo group (n = 13) received an equivalent volume of sterile 0.9% saline solution. Results: The change in the lameness score did not significantly differ between NASHA and placebo groups (P = 0.94). Scores in the flexion test improved more in the NASHA group compared with placebo (P = 0.01). The changes in effusion and pain in flexion were similar (P = 0.94 and P = 0.27, respectively) when NASHA and placebo groups were compared. A telephone interview follow-up of the owners three months post-treatment revealed that 14 of the 21 horses (67%) were able to perform at their previous level of exercise. Conclusions: In the present study, a single IA NASHA injection was not better than a single saline injection for reducing lameness in horses with synovitis or mild osteoarthritis. However, the results of this study indicate that IA NASHA may have some beneficial effects in modifying mild clinical signs but more research is needed to evaluate whether the positive effect documented ie. reduced response in the flexion test is a true treatment effect.
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Publication Date: 2016-03-23 PubMed ID: 27005478PubMed Central: PMC4804525DOI: 10.1186/s12917-016-0687-7Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores the use of non-animal stabilized hyaluronic acid, or NASHA, as a treatment for lameness in horses. It finds that while NASHA did not significantly reduce lameness more than a saline injection, it did help improve results of a flexion test, suggesting there may be some mild beneficial effects.

Objective and Methodology

  • The study aimed to compare the effectiveness of a NASHA treatment against a placebo saline solution for treating lameness in horses stemming from inflammation in the metacarpophalangeal joint (a joint in the horse’s front limb).
  • In order to obtain reliable results, the study was randomized, double-blinded (meaning neither the researchers nor the subjects knew who was getting the treatment or the placebo), and placebo-controlled.
  • 27 horses with clinical lameness were included in the study, of which 14 received the NASHA treatment and 13 received a saline placebo. The effects on lameness, pain, and joint effusion were then observed and compared.

Results

  • The study found that there was no significant difference between the NASHA and placebo groups when it came to an overall change in lameness score.
  • However, scores on the flexion test—a test that measures the horse’s response to the flexion of its joints—showed more improvement in the NASHA group compared to the placebo group.
  • Changes in joint effusion, the accumulation of excess fluid in a joint, and pain were similar in the NASHA and placebo groups.

Conclusions

  • The researchers concluded that NASHA does not significantly reduce lameness more than a saline placebo. However, the improvement seen in the flexion test in the NASHA group indicates that the treatment could have some mild beneficial effects.
  • A follow-up with the owners three months after treatment revealed that 67% of the horses were able to perform at their previous level of exercise, suggesting some level of recovery in the study’s sample.
  • The researchers suggest that more research is needed to understand whether the beneficial effects seen in the flexion test are a genuine result of treatment and what other potential benefits NASHA might have for treating lameness.

Cite This Article

APA
Niemelä TM, Tulamo RM, Hielm-Björkman AK. (2016). A randomised, double-blinded, placebo-controlled clinical study on intra-articular hyaluronan treatment in equine lameness originating from the metacarpophalangeal joint. BMC Vet Res, 12, 60. https://doi.org/10.1186/s12917-016-0687-7

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 12
Pages: 60

Researcher Affiliations

Niemelä, Tytti M
  • Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki,, P.O. Box 57, 00014, Helsinki, Finland. tytti.niemela@helsinki.fi.
Tulamo, Riitta-Mari
  • Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki,, P.O. Box 57, 00014, Helsinki, Finland.
Hielm-Björkman, Anna K
  • Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki,, P.O. Box 57, 00014, Helsinki, Finland.

MeSH Terms

  • Animals
  • Double-Blind Method
  • Female
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / pharmacology
  • Injections, Intra-Articular / veterinary
  • Lameness, Animal / drug therapy
  • Male
  • Metacarpophalangeal Joint / drug effects
  • Treatment Outcome
  • Viscosupplements / administration & dosage
  • Viscosupplements / pharmacology

References

This article includes 47 references
  1. Morris EA, Seeherman HJ. Clinical evaluation of poor performance in the racehorse: the results of 275 evaluations. Equine Vet J 1991;23:169–174.
    doi: 10.1111/j.2042-3306.1991.tb02749.xpubmed: 1884697google scholar: lookup
  2. McIlwraith CW. Pathobiology of joints and their reaction to insult and injury. In: Stashak TS, editor. Adams’ Lameness in Horses. 5. Baltimore: Lippincott Williams & Wilkins; 2001. pp. 469–479.
  3. Buckwalter JA, Brown TD. Joint injury, repair, and remodelling: roles in post-traumatic osteoarthritis. Clin Orthop Rel Res 2004;423:7–16.
    doi: 10.1097/01.blo.0000131638.81519.depubmed: 15232420google scholar: lookup
  4. Caron JP. Osteoarthritis. In: Ross MW, Dyson SJ, editors. Lameness in the Horse. 2. St Louis: Saunders; 2011. pp. 655–668.
  5. Frisbie DD. Synovial joint biology and pathobiology. In: Auer JA, Stick JA, editors. Equine Surgery. 3. St Louis: Saunders; 2006. pp. 1036–55.
  6. Rousseau JC, Delmas PD. Biological markers in osteoarthritis. Nat Clin Pract Rheumatol 2007;3:346–56.
    doi: 10.1038/ncprheum0508pubmed: 17538566google scholar: lookup
  7. Gadher SJ, Woolley DE. Comparative studies on adherent rheumatoid synovial cells in primary culture: characterisation of the dendritic (stellate) cell. Rheumatol Int 1987;7:13–22.
    doi: 10.1007/BF00267337pubmed: 3495852google scholar: lookup
  8. Goldberg VM, Buckwalter JA. Hyaluronans in the treatment of osteoarthritis of the knee: evidence for disease-modifying activity. Osteoarthr Cartilage 2005;13:216–224.
    doi: 10.1016/j.joca.2004.11.010pubmed: 15727888google scholar: lookup
  9. Balazs EA, Denlinger J. Viscosupplementation: a new concept in the treatment of osteoarthritis. J Rheumatol 1993;20(suppl 39):2–9.
    pubmed: 8410881
  10. Åsheim Å, Lindblad G. Intra-articular treatment of arthritis in racehorses with sodium hyaluronate. Acta Vet Scand 1976;17:379–394.
    pmc: PMC8383961pubmed: 1015471
  11. Rose RJ. The intra-articular use of sodium hyaluronate for the treatment of osteoarthrosis in the horse. N Z Vet J 1979;27:5–8.
    doi: 10.1080/00480169.1979.34585pubmed: 286229google scholar: lookup
  12. Auer JA, Fackelman GE, Gingerich DA, Fetter AW. Effect of hyaluronic acid in naturally occurring and experimentally induced osteoarthritis. Am J Vet Res 1980;41:568–574.
    pubmed: 7406275
  13. Ruth DT, Swites BJ. Comparison of the effectiveness of intra-articular hyaluronic acid and conventional therapy for the treatment of naturally occurring arthritic conditions in horses. Equine Pract 1985;7:25–29.
  14. Aviad AD, Arthur RM, Brencick VA, Ferguson HO, Teigland MB. Synacid vs. Hylartin V in equine joint disease. J Equine Vet Sci 1988;8:112–116.
    doi: 10.1016/S0737-0806(88)80030-3google scholar: lookup
  15. Gaustad G, Larsen S. Comparison of polysulphated glycosaminoglycan and sodium hyaluronate with placebo in treatment of traumatic arthritis in horses. Equine Vet J 1995;27:356–362.
    doi: 10.1111/j.2042-3306.1995.tb04070.xpubmed: 8654350google scholar: lookup
  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. Osteoarthr Cartilage 1993;1:97–103.
    doi: 10.1016/S1063-4584(05)80024-Xpubmed: 8886085google scholar: lookup
  17. Åkermark C, Berg P, Björkman A, Malm P. Non-Animal Stabilised Hyaluronic Acid in the Treatment of Osteoarthritis of the Knee: A Tolerability Study. Clin Drug Inv 2002;22:157–166.
    doi: 10.2165/00044011-200222030-00002google scholar: lookup
  18. Altman RD, Åkermark C, Beaulieu AD, Schnitzer T. Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee. Osteoarthr Cartilage 2004;12:642–649.
    doi: 10.1016/j.joca.2004.04.010pubmed: 15262244google scholar: lookup
  19. Balazs EA. Viscosupplementation for treatment of osteoarthritis: from initial discovery to current status and results. Surg Technol Int 2004;12:278–89.
    pubmed: 15455338
  20. Raman R, Dutta A, Day N, Sharma HK, Shaw CJ, Johnson GV. Efficacy of Hylan G-F 20 and Sodium Hyaluronate in the treatment of osteoarthritis of the knee—A prospective randomized clinical trial. Knee 2008;15:318–324.
    doi: 10.1016/j.knee.2008.02.012pubmed: 18430574google scholar: lookup
  21. Abate M, Pulcini D, Di Iorio A, Schivone C. Viscosupplementation with intra-articular hyaluronic acid for treatment of osteoarthritis in the elderly. Curr Pharm Des 2010;16:631–40.
    doi: 10.2174/138161210790883859pubmed: 20388073google scholar: lookup
  22. Chevalier X, Jerosch J, Goupille P, van Dijk N, Luyten FP, Scott DL, Bailleul F, Pavelka K. Single intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, blacebo controlled trial. Ann Rheum Dis 2010;69:113–9.
    pmc: PMC2789938pubmed: 19304567
  23. Arden NK, Åkermark C, Andersson M, Todman MG, Altman RD. A randomized saline-controlled trial of NASHA hyaluronic acid for knee osteoarthritis. Curr Med Res Opin 2014;30:279–286.
    doi: 10.1185/03007995.2013.855631pubmed: 24168077google scholar: lookup
  24. Leighton R, Åkermark C, Therrien R, Richardson JB, Andersson M, Todman MG, Arden NK. NASHA hyaluronic acid vs methylprednisolone for knee osteoarthritis: a prospective, multicentre, randomized, non-inferiority trial. Osteoarthr Cartilage 2014;22:17–25.
    pubmed: 24185114
  25. Frean SP, Abraham LA, Lees P. In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and and carprofen. Res Vet Sci 1999;67:183–90.
    doi: 10.1053/rvsc.1999.0328pubmed: 10502490google scholar: lookup
  26. Brown TJ, Laurent UB, Fraser JR. Turnover of hyaluronan in the synovial joints: elimination of labelled hyaluronan from the knee joint of the rabbit. Exp Physiol 1991;76:125–34.
    doi: 10.1113/expphysiol.1991.sp003474pubmed: 2015069google scholar: lookup
  27. Lindehayn HH, Heilmann HH, Niederhausen HUW, Pohlenz K. Elimination of tritium-labelled hyaluronic acid from normal and osteoarthritic rabbit knee joints. Eur J Chem Clin Biochem 1997;35:355–63.
    pubmed: 9189739
  28. White GW, Stites T, Hamm J, Pool R. Evaluation of the efficacy of various preparations of sodium hyaluronate in an induced equine carpitis model. J Equine Vet Sci 1999;19:331–337.
    doi: 10.1016/S0737-0806(06)82051-4google scholar: lookup
  29. Frisbie DD, Kawack CE, McIlwraith CW, Werpy NM. Evaluation of polysulfated glycosaminoglycan or sodium hyaluronan administered intra-articularly for treatment of horses with experimentally induced osteoarthritis. Am J Vet Res 2009;70:203–209.
    doi: 10.2460/ajvr.70.2.203pubmed: 19231952google scholar: lookup
  30. Kikuchi T, Yamada H, Shimmei M. Effect of high molecular weight hyaluronan on cartilage degradation in a rabbit model of osteoarthritis. Osteoarthr Cartilage 1996;4:99–110.
    doi: 10.1016/S1063-4584(05)80319-Xpubmed: 8806112google scholar: lookup
  31. Shimizu C, Kubo T, Hirasawa Y, Coutts R, Amiel D. Histomorphometric and biochemical effect of various hyaluronans on early osteoarthritis. J Rheumatol 1998;25:1813–1819.
    pubmed: 9733465
  32. Phillips MW. Clinical trial comparison of intra-articular sodium hyaluronate products in the horse. Equine Vet Sci 1989;9:39–40.
    doi: 10.1016/S0737-0806(89)80120-0google scholar: lookup
  33. Edsman K, Hjelm R, Lärkner H, Nord LI, Karlsson A, Wiebensjö Å, Höglund AU, Kenne AH, Näsström J. Intra-articular Duration of Durolane™ after Single Injection into the Rabbit Knee. Cartilage 2011;2(4):384–8.
    pmc: PMC4297137pubmed: 26069596
  34. Lindqvist U, Tolmachev V, Kairemo K, Åström G, Jonsson E, Lundqvist H. Elimination of stabilised hyaluronan from the knee joint in healthy men. Clin Pharmacokinet 2002;41(8):603–613.
    doi: 10.2165/00003088-200241080-00004pubmed: 12102643google scholar: lookup
  35. University of Helsinki - Faculty of Veterinary Medicine. http://www.vetmed.helsinki.fi/english/research/(2010) Accessed 1 April 2010.
  36. Anonymous . Definition and Classification of Lameness. In: Guide for Veterinary Service and Judging of Equestrian Events. Lexington: Amer Assoc Equine Pract; 1991. p. 19.
  37. de Grauw JC, van de Lest CHA, Brama PAJ, Rambags BPB, van Weeren PR. In vivo effects of meloxicam on inflammatory mediators, MMP activity and cartlage biomarkers in equine joints with acute synovitis. Equine Vet J 2009;41:693–699.
    doi: 10.2746/042516409X436286pubmed: 19927589google scholar: lookup
  38. Research randomizer. https://www.randomizer.org/(2010). Accessed 1 Feb 2010
  39. Working in Epidemiology. http://www.winepi.net/uk/index.htm (2010) Accessed 1 Feb 2010
  40. Richette P, Ravaud P, Conrozier T, Euller_Ziegler L, Mazières B, Maugars Y, Mulleman D, Clerson P, Chevalier X. Effect of hyaluronic acid in symptomatic hip osteoarthritis: a multicenter, randomized, placebo-controlled trial. Arthritis Rheum 2009;60:824–30.
    pubmed: 19248105
  41. Pham T, Le Henanff A, Ravaud P, Dieppe P, Paolozzi L, Dougados M. Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis. Ann Rheum Dis 2004;63:1611–1617.
    doi: 10.1136/ard.2003.019703pmc: PMC1754857pubmed: 15331394google scholar: lookup
  42. Gaustad G, Dolvik NI, Larsen S. Comparison of intra-articular injection of 2 ml of 0.9 % NaCl solution with traumatic arthritis. Am J Vet Res 1999;60:1117–1121.
    pubmed: 10490082
  43. Tulamo R-M. 1991. Am J Vet Res. 1991;52:1940–1944.
    pubmed: 1789505
  44. Kearney CM, van Weeren PR, Cornelissen BPM, den Boom P, Brama PAJ. Which anatomical region determines a positive flexion test of the distal aspect of a forelimb in a non-lame horse?. Equine Vet J 2010;42:547–551.
    doi: 10.1111/j.2042-3306.2010.00075.xpubmed: 20716196google scholar: lookup
  45. Antonas KN, Fraser JRE, Muirden KD. Distribution of biologically labelled radioactive hyaluronic acid injected into joints. Ann Rheum Dis 1973;32:103–111.
    doi: 10.1136/ard.32.2.103pmc: PMC1006059pubmed: 4693453google scholar: lookup
  46. Myers SL, Brandt KD, Eilam O. Even low-grade synovitis accelerates the clearance of protein from the canine knee: Implications for the measurement of synovial fluid “markers” of osteoarthritis. Arthr Rheum 1995;38:1085–1091.
    doi: 10.1002/art.1780380810pubmed: 7639804google scholar: lookup
  47. Smith MM, Ghosh P. The 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.
    doi: 10.1007/BF00270463pubmed: 3671989google scholar: lookup

Citations

This article has been cited 5 times.
  1. Lamo-Espinosa JM, Suárez-López Del Amo Á, Núñez-Córdoba JM, Blanco JF, Sánchez M, Moreno V, Cabrera M, Granero-Moltó F, Muiños E, Mazo MM, Crespo-Cullell Í, Mora G, Delgado D, Pompei-Fernández O, Aquerreta JD, Sola MV, Valentí-Azcárate A, Andreu EJ, López-Parra M, Villarón EM, Valentí-Nin JR, Sánchez-Guijo F, Prósper F. Effect of Hyaluronic Acid Compared to Platelet-Rich Plasma as Adjuvants to Bone Marrow Mesenchymal Stem Cell Treatment of Knee Osteoarthritis: Analysis from Two Clinical Trials. Diagnostics (Basel) 2025 Jan 28;15(3).
    doi: 10.3390/diagnostics15030309pubmed: 39941239google scholar: lookup
  2. Mayet A, Zablotski Y, Roth SP, Brehm W, Troillet A. Systematic review and meta-analysis of positive long-term effects after intra-articular administration of orthobiologic therapeutics in horses with naturally occurring osteoarthritis. Front Vet Sci 2023;10:1125695.
    doi: 10.3389/fvets.2023.1125695pubmed: 36908512google scholar: lookup
  3. Jain S, Patil SG, Chinta G, Alluri KV. TamaFlex™-A novel nutraceutical blend improves lameness and joint functions in working horses. Vet Med Sci 2022 Sep;8(5):1936-1945.
    doi: 10.1002/vms3.894pubmed: 35905197google scholar: lookup
  4. Gupta RC, Lall R, Srivastava A, Sinha A. Hyaluronic Acid: Molecular Mechanisms and Therapeutic Trajectory. Front Vet Sci 2019;6:192.
    doi: 10.3389/fvets.2019.00192pubmed: 31294035google scholar: lookup
  5. Niemelä TM, Tulamo RM, Aaltonen K, Sankari SM, Hielm-Björkman AK. Changes in biomarkers in equine synovial fluid two weeks after intra-articular hyaluronan treatment: a randomised double-blind clinical trial. BMC Vet Res 2018 Jun 15;14(1):186.
    doi: 10.1186/s12917-018-1512-2pubmed: 29907111google scholar: lookup
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