FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of veterinary pharmacology and therapeutics2019; 43(1); 38-49; doi: 10.1111/jvp.12818

Evaluation of the inflammatory response to two intra-articular hyaluronic acid formulations in normal equine joints.

Abstract: Intra-articular (IA) hyaluronic acid (HA) is commonly used to treat equine arthritis. Inflammatory response or "joint flare" is a recognized potential side effect. However, the incidence and severity of inflammation following IA HA injection in horses is not well documented. This study compared the effects of two IA HA formulations of different molecular weight (MW) and a saline control on clinical signs and synovial fluid markers of inflammation in normal equine joints. Eight adult horses each had three healthy fetlock joints randomly assigned to treatment with either 1.4 mega Dalton HA, 0.8 mega Dalton HA or saline control once weekly for three weeks. Clinical evaluation and synovial fluid analysis were performed by blinded assessors. Outcomes of interest were lameness score, joint effusion score and synovial fluid white cell count and differential, total protein, viscosity and serum amyloid A. Joints injected with HA developed significant mild-to-moderate inflammatory responses often associated with lameness and joint effusion compared with saline control joints. The higher MW HA formulation elicited a significantly greater inflammatory response than the lower MW HA after the first injection. In HA injected joints, viscosity remained poor for the entire study. Both IA HA formulations in this study induced an inflammatory response in healthy equine joints. This may have implications for the use of HA in equine joints. The findings in this study are limited to the two HA formulations used. Further investigation of different HA formulations and the use of HA in normal and arthritic equine joints is warranted.
© 2019 John Wiley & Sons Ltd.
Get Full Text
Publication Date: 2019-10-29 PubMed ID: 31660636DOI: 10.1111/jvp.12818Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

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 research article analyses the effects of two different molecular weight formulations of intra-articular hyaluronic acid on healthy horse joints, with results showing a mild-to-moderate inflammatory response often leading to lameness and joint effusion.

Objective

The aim of the study was to ascertain the severity and frequency of inflammation in horse joints after they underwent injections with hyaluronic acid. The study also sought to assess and contrast the impacts of two different molecular weight (MW) formulations of hyaluronic acid and a saline solution on markers of inflammation present in synovial fluid in normal horse joints.

Method

  • Eight adult horses were selected, each having three healthy fetlock joints randomly chosen for treatment with 1.4 mega Dalton HA, 0.8 mega Dalton HA, or a saline control. The treatments were administered once a week for three weeks.
  • A clinical evaluation was carried out and synovial fluid was analysed by assessors who were unaware of the treatment the horses had received.
  • The study focused on outcomes such as lameness score, joint effusion score and synovial fluid white cell count and differential, total protein, viscosity and serum amyloid A.

Results

  • The joints subjected to hyaluronic acid surfaced a significant mild-to-moderate inflammatory reaction frequently associated with lameness and joint effusion, in comparison to joints that received saline treatment.
  • The formulation with the higher MW induced a notably higher inflammatory response than the lower MW version after the first injection.
  • Throughout the entire study, the viscosity in joints injected with HA remained poor.

Conclusion

Both hyaluronic acid formulations used in this research led to an inflammatory response in healthy horse joints. This could be a consideration for the future use of hyaluronic acid in horse joints. The conclusions from this research are limited to the specific hyaluronic acid formulations studied. As such, further research is recommended using a variety of hyaluronic acid formulations on both healthy and arthritic horse joints.

Cite This Article

APA
Johnston GCA, Wood KA, Jackson KV, Perkins NR, Zedler ST. (2019). Evaluation of the inflammatory response to two intra-articular hyaluronic acid formulations in normal equine joints. J Vet Pharmacol Ther, 43(1), 38-49. https://doi.org/10.1111/jvp.12818

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 43
Issue: 1
Pages: 38-49

Researcher Affiliations

Johnston, Georgina C A
  • School of Veterinary Science, University of Queensland, Gatton, Qld, Australia.
Wood, Kelly A
  • School of Veterinary Science, University of Queensland, Gatton, Qld, Australia.
Jackson, Karen V
  • School of Veterinary Science, University of Queensland, Gatton, Qld, Australia.
Perkins, Nigel R
  • School of Veterinary Science, University of Queensland, Gatton, Qld, Australia.
Zedler, Steven T
  • School of Veterinary Science, University of Queensland, Gatton, Qld, Australia.

MeSH Terms

  • Animals
  • Drug Compounding
  • Erythrocyte Count
  • Female
  • Horses / metabolism
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / adverse effects
  • Hyaluronic Acid / chemistry
  • Inflammation
  • Injections, Intra-Articular
  • Lameness, Animal / chemically induced
  • Male
  • Synovial Fluid / chemistry
  • Synovial Fluid / cytology

Grant Funding

  • Randlab Pty Ltd
  • University of Queensland School of Veterinary Science

References

This article includes 58 references
  1. Altman RD, Akermark 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 12, 642-649.
    doi: 10.1016/j.joca.2004.04.010google scholar: lookup
  2. Andreasson SM, Vinther AML, Nielsen SS, Andersen PH, Tnibar A, Kristensen AT, Jacobsen S. Changes in concentrations of haemostatic and inflammatory biomarkers in synovial fluid after intra-articular injection of lipopolysaccharide in horses. BMC Veterinary Research 13, 182.
    doi: 10.1186/s12917-017-1089-1google scholar: lookup
  3. Antonacci JM, Schmidt TA, Serventi LA, Cai MZ, Shu YL, Schumacher BL, Sah RL. Effects of equine joint injury on boundary lubrication of articular cartilage by synovial fluid: Role of hyaluronan. Arthritis & Rheumatism 64, 2917-2926.
    doi: 10.1002/art.34520google scholar: lookup
  4. Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: A systematic review and network meta-analysis. Annals of Internal Medicine 162(1), 46-54.
    doi: 10.7326/m14-1231google scholar: lookup
  5. Concoff A, Sanchetti P, Niazi F, Shaw P, Rosen J. The efficacy of multiple versus single hyaluronic acid injections: A systematic review and meta-analysis. BMC Musculoskeletal Disorders 18, 542.
    doi: 10.1186/s12891-017-1897-2google scholar: lookup
  6. Conrozier T, Vignon E. Is there evidence to support the inclusion of viscosupplementation in the treatment paradigm for patients with hip osteoarthritis?. Clinical and Experimental Rheumatology 23(5), 711-716.
  7. Dahl LB, Dahl IM, Engstrom-Laurent A, Granath K. Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies. Annals of the Rheumatic Diseases 44, 817-822.
    doi: 10.1136/ard.44.12.817google scholar: lookup
  8. Davis WH Jr, Lee SL, Sokoloff L. Boundary lubricating ability of synovial fluid in degenerative joint disease. Arthritis and Rheumatism 21, 754-760.
    doi: 10.1002/art.1780210703google scholar: lookup
  9. de Grauw JC, Visser-Meijer MC, Lashley F, Meeus P, van Weeren PR. Intra-articular treatment with triamcinolone compared with triamcinolone with hyaluronate: A randomised open-label multicentre clinical trial in 80 lame horses. Equine Veterinary Journal 48, 152-158.
    doi: 10.1111/evj.12383google scholar: lookup
  10. Elsaid KA, Jay GD, Warman ML, Rhee DK, Chichester CO. Association of articular cartilage degradation and loss of boundary-lubricating ability of synovial fluid following injury and inflammatory arthritis. Arthritis and Rheumatism 52, 1746-1755.
    doi: 10.1002/art.21038google scholar: lookup
  11. Fam H, Bryant JT, Kontopoulou M. Rheological properties of synovial fluids. Biorheology 44(2), 59-74.
  12. Francoz D, Derochers A, Latouche JS. Effect of repeated arthrocentesis and single joint lavage on cytologic evaluation of synovial fluid in 5 young. .
  13. Frisbie DD, Kawcak CE, McIlwraith CW, Werpy NM. Evaluation of polysulfated glycosaminoglycan or sodium hyaluronan administered intra-articularly for treatment of horses with experimentally induced osteoarthritis. American Journal of Veterinary Research 70(2), 203-209.
  14. Fuller CJ, Bladon BM, Driver AJ, Barr ARS. The intra- and inter-assessor reliability of measurement of functional outcome by lameness scoring in horses. The Veterinary Journal 171, 281-286.
  15. Gaustad G, Larsen S. Comparison of polysulphated glycosaminoglycan and sodium hyaluronate with placebo in treatment of traumatic arthritis in horses. Equine Veterinary Journal 27(5), 356-362.
  16. Goldberg VM, Coutts RD. Pseudoseptic reactions to hylan viscosupplementation: Diagnosis and treatment. Clinical Orthopaedics and Related Research 419, 130-137.
    doi: 10.1097/00003086-200402000-00021google scholar: lookup
  17. Hasselbacher P. Measuring synovial fluid viscosity with a white blood cell diluting pipette. Arthritis and Rheumatism 19, 1358-1362.
  18. He WW, Kuang MJ, Zhao J, Sun L, Lu B, Wang Y, Ma XL. Efficacy and safety of intraarticular hyaluronic acid and corticosteroid for knee osteoarthritis: A meta-analysis. International Journal of Surgery 39, 95-103.
    doi: 10.1016/j.ijsu.2017.01.087google scholar: lookup
  19. Hilbert BJ, Rowley G, Antonass KN, McGILL CA, Reynoldson JA, Hawkins CD. Changes in the synovia after the intra-articular injection of sodium hyaluronate into normal horse joints and after arthrotomy and experimental cartilage damage. Australian Veterinary Journal 62(6), 182-184.
    doi: 10.1111/j.1751-0813.1985.tb07290.xgoogle scholar: lookup
  20. Hollander JL, Reginato AJ, Torralba TP. Examination of synovial fluid as a diagnostic aid in arthritis. Medical Clinics of North America 50, 1281-1293.
    doi: 10.1016/s0025-7125(16)33125-xgoogle scholar: lookup
  21. Jacobsen S, Niewold TA, Halling-Thomsen M, Nanni S, Olsen E, Lindegaard C, Anderson PH. Serum amyloid A isoforms in serum and synovial fluid in horses with lipopolysaccharide-induced arthritis. Veterinary Immunology and Immunopathology 110, 325-330.
    doi: 10.1016/j.vetimm.2005.10.012google scholar: lookup
  22. Jacobsen S, Thomsen MH, Nanni S. Concentrations of serum amyloid A in serum and synovial fluid from healthy horses and horses with joint disease. American Journal of Veterinary Research 67, 1738-1742.
    doi: 10.2460/ajvr.67.10.1738google scholar: lookup
  23. Jay GD, Torres JR, Warman ML, Laderer MC, Breuer KS. The role of lubricin in the mechanical behavior of synovial fluid. Proceedings of the National Academy of Sciences USA 104(15), 6194-6199.
    doi: 10.1073/pnas.0608558104google scholar: lookup
  24. Jevsevar D, Donnelly P, Brown GA, Cummins DS. Viscosupplementation for osteoarthritis of the Knee. Journal of Bone and Joint Surgery-American Volume 97, 2047-2060.
    doi: 10.2106/jbjs.n.00743google scholar: lookup
  25. Johansen M, Bahrt H, Altman RD, Bartels EM, Juhl CB, Bliddal H, Christensen R. Exploring reasons for the observed inconsistent trial reports on intra-articular injections with hyaluronic acid in the treatment of osteoarthritis: Meta-regression analyses of randomized trials. Seminars in Arthritis and Rheumatism 46, 34-48.
    doi: 10.1016/j.semarthrit.2016.02.010google scholar: lookup
  26. Keegan KG, Dent EV, Wilson DA, Janicek J, Kramer J, Lacarrubba A, Norris T. Repeatability of subjective evaluation of lameness in horses. Equine Veterinary Journal 42, 92-97.
  27. Koenig TJ, Dart AJ, Mcilwraith CW, Horadagoda N, Bell RJ, Perkins N, Little CB. Treatment of experimentally induced osteoarthritis in horses using an intravenous combination of sodium pentosan polysulfate, N-acetyl glucosamine, and sodium hyaluronan. Veterinary Surgery 43, 612-622.
    doi: 10.1111/j.1532-950x.2014.12203.xgoogle scholar: lookup
  28. Kuemmerle JM, Uhlig H, Kofler J. Severe acute inflammatory reaction (SAIR) of the fetlock joint after intraarticular hyaluronate injection in a horse. Veterinary and Comparative Orthopaedics and Traumatology 19, 236-238.
    doi: 10.1055/s-0038-1633006google scholar: lookup
  29. Kwan C, Bell R, Koenig T, Bischofberger A, Horadagoda N, Perkins NR, Dart AJ. Effects of intra-articularsodium pentosan polysulfate and glucosamine on the cytology, total protein concentration and viscosity of synovial fluid in horses. Australian Veterinary Journal 90(8), 315-320.
    doi: 10.1111/j.1751-0813.2012.00959.xgoogle scholar: lookup
  30. Lindegaard C, Gleerup KB, Thomsen MH, Martinussen T, Jacobsen S, Andersen PH. Anti-inflammatory effects of intra-articular administration of morphine in horses with experimentally induced synovitis. American Journal of Veterinary Research 71(1), 69-75.
  31. Lo GH, Lavalley M, Mcalindon T, Felson DT. Intra-articular hyaluronic acid in treatment of knee osteoarthritis. JAMA 290(23), 3115-3121.
    doi: 10.1001/jama.290.23.3115google scholar: lookup
  32. Ludwig KE, Weise RB, Graham MR, Tyler AJ, Settlage JM, Werre SR, Dahlgren LA. Serum and synovial fluid serum amyloid a response in equine models of synovitis and septic arthritis. Veterinary Surgery 45, 859-867.
    doi: 10.1111/vsu.12531google scholar: lookup
  33. Ludwig TE, Cowman MK, Jay GD, Schmidt TA. Effects of concentration and structure on proteoglycan 4 rheology and interaction with hyaluronan. Biorheology 51(6), 409-422.
  34. Maheu E, Rannou F, Reginster JY. Efficacy and safety of hyaluronic acid in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Seminars in Arthritis and Rheumatism 45(4 Suppl), 28-33.
    doi: 10.1016/j.semarthrit.2015.11.008google scholar: lookup
  35. Martin-Alarcon L, Schmidt TA. Rheological effects of macromolecular interactions in synovial fluid. Biorheology 53(2), 49-56.
    doi: 10.3233/bir-15104google scholar: lookup
  36. Miller L, Block J. US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: Systematic review and meta-analysis of randomized, saline-controlled trials. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders 6, 57-63.
    doi: 10.4137/cmamd.s12743google scholar: lookup
  37. Neu CP, Reddi AH, Komvopoulos K, Schmid TM, Di Cesare PE. Increased friction coefficient and superficial zone protein expression in patients with advanced osteoarthritis. Arthritis and Rheumatism 62, 2680-2687.
    doi: 10.1002/art.27577google scholar: lookup
  38. Niemela TM, Tulamo RM, Aaltonen K, Sankari SM, Hielm-Bjorkman AK. Changes in biomarkers in equine synovial fluid two weeks after intra-articular hyaluronan treatment: A randomised double-blinded clinical trial. BMC Veterinary Research 14, 186.
  39. Niemela TM, Tulamo RM, Carmona JU, Lopez C. Evaluation of the effect of experimentally induced cartilage defect and intra-articualr hyaluronan on synovial fluid biomarkers in intercarpal joints of horses. Acta Veterinaria Scandinavica 61, 24.
  40. Niemela TM, Tulamo RM, Hielm-Bjorkman AK. A randomised, double-blinded, placebo-controlled clinical study on intra-articular hyaluronan treatment in equine lameness originating from the metacarpophalangeal joint. BMC Veterinary Research 12, 60.
    doi: 10.1186/s12917-016-0687-7google scholar: lookup
  41. Ogston AG, Stanier JE. The physiological function of hyaluronic acid in synovial fluid: Viscous, elastic and lubricant properties. Journal of Physiology 119, 244-252.
  42. O'Hanlon CE, Newberry SJ, Booth M, Grant S, Motala A, Maglione MA, Shekelle PG. Hyaluronic acid injection therapy for osteoarthritis of the knee: Concordant efficacy and conflicting serious adverse events in two systematic reviews. Systematic Reviews 5, 186.
    doi: 10.1186/s13643-016-0363-9google scholar: lookup
  43. Pullman-Mooar S, Mooar P, Sieck M, Clayburne G, Schumacher HR. Are there distinctive inflammatory flares after hylan g-f 20 intraarticular injections?. Journal of Rheumatology 29(12), 2611-2614.
  44. Rayahin JE, Buhrman JS, Zhang Y, Koh TJ, Gemeinhart RA. High and low molecular weight hyaluronic acid diferentially influence macrophage activation. ACS Biomaterials Science and Engineering 1, 481-493.
  45. Roneus B, Lindblad A, Lindholm A, Jones B. Effects of intra-articular corticosteroids and sodium hyaluronate injections on synovial fluid production and synovial fluid content of sodium hyaluronate and proteoglycans in normal equine joints. Zentralbl Veterinarmed A 40(1), 10-16.
  46. 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 Practice 7(1), 25-29.
  47. Rutjes AWS, Juni P, da Costa BR, Trelle S, Nuesch E, Reichenbach S. Viscosupplementation for osteoarthritis of the knee: A systematic review and meta-analysis. Annals of Internal Medicine 157(3), 180-191.
    doi: 10.7326/0003-4819-157-3-201208070-00473google scholar: lookup
  48. Sanchez-Teran AF, Bracamonte JL, Hendrick S, Riddell L, Musil K, Hoff B, Rubio-Martinez LM. Effect of repeated through-and-through joint lavage on serum amyloid A in synovial fluid from healthy horses. The Veterinary Journal 210, 30-33.
    doi: 10.1016/j.tvjl.2016.01.001google scholar: lookup
  49. Sarma AV, Powell GL, Laberge M. Phospholipid composition of articular cartilage boundary lubricant. Journal of Orthopaedic Research 19, 671-676.
    doi: 10.1016/s0736-0266(00)00064-4google scholar: lookup
  50. Schwarz IM, Hills BA. Surface-active phospholipids as the lubricating component of lubricin. British Journal of Rheumatology 37, 21-26.
  51. Steel CM. Equine synovial fluid analysis. The Veterinary Clinics of North America. Equine Practice 24, 437-454.
    doi: 10.1016/j.cveq.2008.05.004google scholar: lookup
  52. Swann DA, Silver FH, Slayter HS, Stafford W, Shore E. The molecular structure and lubricating activity of lubricin isolated from bovine and human synovial fluids. The Biochemical Journal 225, 195-201.
    doi: 10.1042/bj2250195google scholar: lookup
  53. Tulamo RM. Comparison of high-performance liquid chromatography with a radiometric assay for determination of the effect of intra-articular administration of corticosteroid and saline solution on synovial fluid hyaluronate concentration in horses. American Journal of Veterinary Research 52, 1940-1944.
  54. Tulamo RM, Heiskanen T, Salonen M. Concentration and molecular weight distribution of hyaluronate in synovial fluid from clinically normal horses and horses with diseased joints. American Journal of Veterinary Research 55(5), 710-715.
  55. Van Weeren PR, De Grauw JC. Pain in osteoarthritis. Veterinary Clinics of North America Equine Practice 26, 619-642.
    doi: 10.1016/j.cveq.2010.07.007google scholar: lookup
  56. White KK, Hodgson DR, Hancock D, Parry BW, Cordell C. Changes in equine carpal joint synovial fluid in response to injection of two anaesthetic agents. Cornell Veterinarian 79, 25-28.
  57. Wong BL, Kim SH, Antonacci JM, Mcilwraith CW, Sah RL. Cartilage shear dynamics during tibio-femoral articulation: Effect of acute joint injury and tribosupplementation on synovial fluid lubrication. Osteoarthritis Cartilage 18, 464-471.
    doi: 10.1016/j.joca.2009.11.008google scholar: lookup
  58. Zubrod CJ, Farnsworth KD, Oaks JL. Evaluation of arthrocentesis site bacterial flora before and after 4 methods of preparation in horses with and without evidence of skin contamination. Veterinary Surgery 33, 525-530.
    doi: 10.1111/j.1532-950x.2004.04074.xgoogle scholar: lookup

Citations

This article has been cited 5 times.
  1. Bertone AL, Reinemeyer C, Tsaprailis G, Ragland D, Leise B. Cryopreserved equine umbilical cord tissue allograft characterization and biocompatibility in vivo in musculoskeletal tissues: a controlled study. BMC Med 2025 Jul 23;23(1):439.
    doi: 10.1186/s12916-025-04231-7pubmed: 40702469google scholar: lookup
  2. Terlinden A, Jacquet S, Manivong S, Cullier A, Cassé F, Legendre F, Garcia AA, Roullin G, Moldovan F, Sirois P, Banquy X, Galéra P, Audigié F, Demoor M, Bertoni L. Double-blinded, randomized tolerance study of a biologically enhanced Nanogel with endothelin-1 and bradykinin receptor antagonist peptides via intra-articular injection for osteoarthritis treatment in horses. BMC Vet Res 2024 Dec 4;20(1):547.
    doi: 10.1186/s12917-024-04352-wpubmed: 39633332google scholar: lookup
  3. Pereira MF, Ribeiro G, Gonzales A, Arantes JA, Dória RGS. Effects of intra-articular administration of hyaluronic acid or platelet-rich plasma as a complementary treatment to arthroscopy in horses with osteochondritis dissecans. Vet Anim Sci 2024 Mar;23:100330.
    doi: 10.1016/j.vas.2023.100330pubmed: 38259325google scholar: lookup
  4. Song Y, Day CM, Afinjuomo F, Tan JE, Page SW, Garg S. Advanced Strategies of Drug Delivery via Oral, Topical, and Parenteral Administration Routes: Where Do Equine Medications Stand?. Pharmaceutics 2023 Jan 4;15(1).
    doi: 10.3390/pharmaceutics15010186pubmed: 36678815google scholar: lookup
  5. Cokelaere SM, Groen WMGAC, Plomp SGM, de Grauw JC, van Midwoud PM, Weinans HH, van de Lest CHA, Tryfonidou MA, van Weeren PR, Korthagen NM. Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG(1000)]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints. Pharmaceutics 2021 Sep 10;13(9).
    doi: 10.3390/pharmaceutics13091438pubmed: 34575514google scholar: lookup
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.