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Equine veterinary journal2022; 55(5); 905-915; doi: 10.1111/evj.13899

Residual effects of intra-articular betamethasone and triamcinolone acetonide in an equine acute synovitis model.

Abstract: Intra-articular (IA) corticosteroids are regularly used in equine athletes for the control of joint inflammation. Objective: The goal of this study was to use an acute synovitis inflammation model to determine the residual effects of IA betamethasone and triamcinolone acetonide on various inflammatory parameters and lameness. Methods: Crossover randomised trial. Methods: Five mixed-breed, 2-year-old horses were randomly allocated to an IA treatment of the radiocarpal joint with 9 mg of either betamethasone or triamcinolone acetonide. Two weeks following treatment, horses were injected with 1 μg of lipopolysaccharide (LPS) diluted in 1 ml of saline. Following LPS injection, horses were crossed-over and both sets of injections were repeated after a washout period. Blood samples were collected at multiple time points for mRNA analysis, as well as serum amyloid A (SAA) and cortisol determination. At each time point, lameness was also subjectively scored. Additional injections with saline-only or LPS-only (twice) were conducted as negative and positive controls, respectively. Two-way repeated measures analysis of variance was used to analyse all data. Results: Corticosteroid-only treatments result in significant mRNA expression differences, as well as significant and prolonged cortisol suppression. Following LPS injection, there was a residual treatment effect with triamcinolone evidenced by a significant treatment effect on IL-6 and PTGS1 (cyclooxygenase-1), lameness, SAA and cortisol concentrations, while only IL-6 expression was affected by betamethasone. Conclusions: The acute synovitis model used here results in significant inflammation and is not representative of the low-grade inflammation seen with typical joint disease and residual anti-inflammatory effects may be more profound in naturally occurring joint disease. Conclusions: Current regulatory guidelines may be insufficient if the concern is residual anti-inflammatory effects. Additionally, intra-articular corticosteroid administration is not without risk, as evidenced by a significant suppression of serum cortisol concentration and, as such, the benefits of their administration should be weighed against those risks.
Publication Date: 2022-12-01 PubMed ID: 36397207DOI: 10.1111/evj.13899Google Scholar: Lookup
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  • Randomized Controlled Trial
  • Veterinary
  • Journal Article

Summary

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The research paper details a study on the residual effects of intra-articular betamethasone and triamcinolone acetonide, two types of corticosteroids, in a model of equine acute synovitis, which is a condition characterized by joint inflammation. The primary focus was to see how these drugs impacted different factors relating to inflammation and lameness.

Methodology

  • The study was conducted as a crossover randomised trial with five mixed-breed, 2-year-old horses being the subjects.
  • Each horse was randomly allocated to treatment with either 9mg of betamethasone or triamcinolone acetonide in the radiocarpal joint, a joint in the forelimb of the horse.
  • After two weeks, the horses were injected with lipopolysaccharide (LPS) – a molecule that induces inflammation – which was diluted in 1ml of saline.
  • Following this, they were switched (crossed-over) to the other drug and the same procedure was followed.
  • Blood samples were collected at different intervals to monitor mRNA expressions, and levels of serum amyloid A (SAA), and cortisol.
  • Lameness in the horses was also subjectively scored at each interval.
  • Additional injections of just saline or LPS were given, acting as negative and positive controls, respectively. The researchers used two-way repeated measures analysis of variance to analyze the data.

Results

  • The corticosteroid injections resulted in significant differences in mRNA expression and sustained suppression of cortisol.
  • Following LPS injection, there was a noticeable residual treatment effect from triamcinolone, evidenced by a significant treatment effect on IL-6 and PTGS1 (two explanatory genes of inflammation), lameness, SAA, and cortisol levels.
  • However, only IL-6 expression was impacted by betamethasone treatment.

Conclusions

  • The researchers concluded that the model of acute synovitis used in this research leads to significant inflammation and doesn’t represent the mild inflammation typically seen with joint disease.
  • They also suggested that current regulations may not be adequate if the residual anti-inflammatory effects of these drugs are a concern.
  • Furthermore, intra-articular corticosteroid administration poses a risk, as shown by the significant suppression of serum cortisol concentration, so one must carefully consider the benefits and risks before such administration.

Cite This Article

APA
Partridge E, Adam E, Wood C, Parker J, Johnson M, Horohov D, Page A. (2022). Residual effects of intra-articular betamethasone and triamcinolone acetonide in an equine acute synovitis model. Equine Vet J, 55(5), 905-915. https://doi.org/10.1111/evj.13899

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 55
Issue: 5
Pages: 905-915

Researcher Affiliations

Partridge, Emma
  • Department of Veterinary Science, University of Kentucky, Maxwell H. Gluck Equine Research Center, Lexington, Kentucky, USA.
Adam, Emma
  • Department of Veterinary Science, University of Kentucky, Maxwell H. Gluck Equine Research Center, Lexington, Kentucky, USA.
Wood, Courtney
  • Lincoln Memorial University, Harrogate, Tennessee, USA.
Parker, Jordan
  • Department of Veterinary Science, University of Kentucky, Maxwell H. Gluck Equine Research Center, Lexington, Kentucky, USA.
Johnson, Mackenzie
  • Department of Veterinary Science, University of Kentucky, Maxwell H. Gluck Equine Research Center, Lexington, Kentucky, USA.
Horohov, David
  • Department of Veterinary Science, University of Kentucky, Maxwell H. Gluck Equine Research Center, Lexington, Kentucky, USA.
Page, Allen
  • Department of Veterinary Science, University of Kentucky, Maxwell H. Gluck Equine Research Center, Lexington, Kentucky, USA.

MeSH Terms

  • Horses
  • Animals
  • Triamcinolone Acetonide / therapeutic use
  • Betamethasone / therapeutic use
  • Hydrocortisone
  • Lipopolysaccharides
  • Lameness, Animal / drug therapy
  • Interleukin-6
  • Synovitis / chemically induced
  • Synovitis / drug therapy
  • Synovitis / veterinary
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / veterinary
  • Joint Diseases / veterinary
  • Anti-Inflammatory Agents
  • Injections, Intra-Articular / veterinary
  • Horse Diseases / drug therapy
  • Horse Diseases / metabolism

Grant Funding

  • Jes E. and Clementine M. Schlaikjer Endowment at the University of Kentucky
  • Lincoln Memorial University
  • Zoetis

References

This article includes 46 references
  1. Wilsher S, Allen WR, Wood JL. Factors associated with failure of thoroughbred horses to train and race.. Equine Vet J 2006;38(2):113-8.
  2. Dyson PK, Jackson BF, Pfeiffer DU, Price JS. Days lost from training by two- and three-year-old thoroughbred horses: a survey of seven UK training yards.. Equine Vet J 2008;40(7):650-7.
  3. Rossdale P, Hopes R, Digby N. Epidemiological study of wastage among racehorses 1982 and 1983.. Vet Rec 1985;116(3):66-9.
  4. Jackman BR. Common lameness in the cutting and reining horse.. Proc Am Assoc Equine Pract 2001;47:6-11.
  5. Bailey CJ, Reid SW, Hodgson DR, Rose RJ. Impact of injuries and disease on a cohort of two- and three-year-old thoroughbreds in training.. Vet Rec 1999;145(17):487-93.
  6. Ferris DJ, Frisbie DD, McIlwraith CW, Kawcak CE. Current joint therapy usage in equine practice: a survey of veterinarians 2009.. Equine Vet J 2011;43(5):530-5.
  7. Zanotto GM, Frisbie DD. Current joint therapy usage in equine practice: changes in the last 10 years.. Equine Vet J 2022;54(4):750-6.
  8. Whitton RC, Jackson MA, Campbell AJD, Anderson GA, Parkin TDH, Morton JM. Musculoskeletal injury rates in thoroughbred racehorses following local corticosteroid injection.. Vet J 2014;200(1):71-6.
  9. McIlwraith CW. The use of intra-articular corticosteroids in the horse: what is known on a scientific basis?. Equine Vet J 2010;42(6):563-71.
  10. Caron JP. Intra-articular injections for joint disease in horses.. Vet Clin North Am Equine Pract 2005;21(3):559-73.
  11. Gray RG, Tenenbaum J, Gottlieb NL. Local corticosteroid injection treatment in rheumatic disorders.. Semin Arthritis Rheum 1981;10:231-54.
  12. Masferrer J, Seibert K. Regulation of prostaglandin synthesis by glucocorticoids.. Receptor 1994;4(1):25-30.
  13. Wernecke C, Braun HJ, Dragoo JL. The effect of intra-articular corticosteroids on articular cartilage: a systematic review.. Orthop J Sports Med 2015;3(5):1-7.
  14. Riggs CM. Intra-articular corticosteroids under threat in thoroughbred racehorse practice.. Vet J 2014;200(1):1-2.
  15. Martig S, Chen W, Lee PVS, Whitton RC. Bone fatigue and its implications for injuries in racehorses.. Equine Vet J 2014;46(4):408-15.
  16. Barr ED, Pinchbeck GL, Clegg PD, Boyde A, Riggs CM. Post mortem evaluation of palmar osteochondral disease (traumatic osteochondrosis) of the metacarpo/metatarsophalangeal joint in thoroughbred racehorses.. Equine Vet J 2009;41(4):366-71.
  17. O'Brien T, Baker TA, Brounts SH, Sample SJ, Markel MD, Scollay MC. Detection of articular pathology of the distal aspect of the third metacarpal bone in thoroughbred racehorses: comparison of radiography, computed tomography and magnetic resonance imaging.. Vet Surg 2011;40(8):942-51.
  18. Tranquille CA, Parkin TDH, Murray RC. Magnetic resonance imaging-detected adaptation and pathology in the distal condyles of the third metacarpus, associated with lateral condylar fracture in thoroughbred racehorses.. Equine Vet J 2012;44(6):699-706.
  19. Riggs CM, Whitehouse GH, Boyde A. Pathology of the distal condyles of the third metacarpal and third metatarsal bones of the horse.. Equine Vet J 1999;31(2):140-8.
  20. Knych HK, Vidal MA, Chouicha N, Mitchell M, Kass PH. Cytokine, catabolic enzyme and structural matrix gene expression in synovial fluid following intra-articular administration of triamcinolone acetonide in exercised horses.. Equine Vet J 2017;49(1):107-15.
  21. Page AE, Adam E, Arthur R, Barker V, Franklin F, Friedman R. Expression of select mRNA in thoroughbreds with catastrophic racing injuries.. Equine Vet J 2022;54(1):63-73.
  22. Page AE, Stewart JC, Holland RE Jr, Horohov DW. The impact of training regimen on the inflammatory response to exercise in 2-year-old thoroughbreds.. J Equine Vet 2017;58:78-83.
  23. Horohov DW, Sinatra ST, Chopra RK, Jankowitz S, Betancourt A, Bloomer RJ. The effect of exercise and nutritional supplementation on proinflammatory cytokine expression in young racehorses during training.. J Equine Vet 2012;32(12):805-15.
  24. Page AE, Adam E, Stewart JC, Gonzales C, Barker V, Horohov DW. Alterations of peripheral gene expression in response to lipopolysaccharide-induced synovitis as a model for inflammation in horses.. Vet Immunol Immunopathol 2020;225:110058.
  25. Page AE, Wood C, Partridge E, Horohov DW, Adam E. Equine peripheral gene expression changes in response to dose-dependent lipopolysaccharide-induced synovitis.. J Equine Vet 2022;109:103828.
  26. . Lameness Exams: Evaluating the Lame Horse.. .
  27. Hunt CL, Leatherwood JL, Coverdale JA, Sigler DL, Vogelsang MM, Arnold CE. Effects of repeated arthrocentesis on systemic cytokine expression and leukocyte population in young horses challenged with intra-articular lipopolysaccharide.. J Anim Sci 2018;97(1):184-91.
  28. Page AE, Stewart JC, Fielding CL, Horohov DW. The effect of a 160-kilometer competitive endurance ride on inflammatory marker mRNA expression in horses.. J Equine Vet 2019;79:45-9.
  29. Breathnach CC, Sturgill-Wright T, Stiltner JL, Adams AA, Lunn DP, Horohov DW. Foals are interferon gamma-deficient at birth.. Vet Immunol Immunopathol 2006;112(3-4):199-209.
  30. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method.. Methods (San Diego, CA) 2001;25(4):402-8.
  31. . March 2022.. .
  32. Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR. Treatment effects of intra-articular triamcinolone acetonide in an equine model of recurrent joint inflammation.. Equine Vet J 2021;53(6):1277-86.
  33. Vane J, Botting R. Inflammation and the mechanism of action of anti-inflammatory drugs.. FASEB J 1987;1(2):89-96.
  34. Barnes PJ. How corticosteroids control inflammation: quintiles prize lecture 2005.. Br J Pharmacol 2006;148(3):245-54.
  35. Knych HK, Vidal MA, Casbeer HC, McKemie DS. Pharmacokinetics of triamcinolone acetonide following intramuscular and intra-articular administration to exercised thoroughbred horses.. Equine Vet J 2013;45(6):715-20.
  36. Tanaka T, Narazaki M, Kishimoto T. Il-6 in inflammation, immunity, and disease.. Perspect Biol 2014;6(10):a016295.
  37. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6.. Biochim Biophys Acta. Mol Cell Res 2011;1813(5):878-88.
  38. Knych HK, Stanley SD, Harrison LM, Mckemie DS. Pharmacokinetics of betamethasone in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses.. Drug Test Anal 2017;9(9):1385-91.
  39. Tanabe T, Tohnai N. Cyclooxygenase isozymes and their gene structures and expression.. Prostaglandins 2002;68:95-114.
  40. . Current Model Rules and Standards. December 2020.. .
  41. . 2022 USEF Guidelines & Rules for Drugs and Medications. 2021 December 2021.. .
  42. Karam B, Hines S, Skipper L, Pusterla N. Whole-blood validation of a new point-of-care equine serum amyloid a assay.. J Equine Vet 2020;94:103222.
  43. Hapgood JP, Avenant C, Moliki JM. Glucocorticoid-independent modulation of GR activity: implications for immunotherapy.. Pharmacol Ther 2016;165:93-113.
  44. Cui L, Wang Y, Wang H, Dong J, Li Z, Li J. Different effects of cortisol on pro-inflammatory gene expressions in LPS-, heat-killed E. coli-, or live E. coli-stimulated bovine endometrial epithelial cells.. BMC Vet Res 2020;16(1):9.
  45. Stahn C, Löwenberg M, Hommes DW, Buttgereit F. Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists.. Mol Cell Endocrinol 2007;275(1):71-8.
  46. Deng Q, Riquelme D, Trinh L, Low MJ, Tomic M, Stojilkovic S. Rapid glucocorticoid feedback inhibition of ACTH secretion involves ligand-dependent membrane association of glucocorticoid receptors.. Endocrinology 2015;156(9):3215-27.

Citations

This article has been cited 3 times.
  1. Duggan MJS, Kearney C, Baltrimaite M, Labberté MC, Gibney R, Brama PAJ. Refinement of the Lipopolysaccharide-Induced Synovitis Model in Equine Middle Carpal Joints. Animals (Basel) 2025 Aug 22;15(17).
    doi: 10.3390/ani15172474pubmed: 40941269google scholar: lookup
  2. Page AE, Johnson M, Parker JL, Jacob O, Poston R, Adams AA, Adam EN. The Effects of Intra-Articular Triamcinolone and Autologous Protein Solution on Metabolic Parameters in Horses. Animals (Basel) 2024 Aug 2;14(15).
    doi: 10.3390/ani14152250pubmed: 39123776google scholar: lookup
  3. Finding EJT, Faulkner A, Nash L, Wheeler-Jones CPD. Equine Endothelial Cells Show Pro-Angiogenic Behaviours in Response to Fibroblast Growth Factor 2 but Not Vascular Endothelial Growth Factor A. Int J Mol Sci 2024 May 30;25(11).
    doi: 10.3390/ijms25116017pubmed: 38892205google scholar: lookup