Analyze Diet
Equine veterinary journal2020; 53(6); 1277-1286; doi: 10.1111/evj.13396

Treatment effects of intra-articular triamcinolone acetonide in an equine model of recurrent joint inflammation.

Abstract: Intra-articular triamcinolone acetonide is a widely used treatment for joint inflammation despite limited scientific evidence of its efficacy. Objective: To investigate if intra-articular triamcinolone acetonide has sustained anti-inflammatory effects using an equine model of repeated joint inflammation. Methods: Randomised controlled experimental study. Methods: For three consecutive cycles 2 weeks apart, inflammation was induced in both middle carpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After the first LPS injection only, treatment with 12 mg triamcinolone acetonide (TA) followed in one randomly assigned joint, while the contralateral joint was treated with sterile saline (control). Clinical parameters (composite welfare scores, joint effusion, joint circumference) were recorded and synovial fluid samples were analysed for various biomarkers (total protein, WBCC; PGE ; CCL2; TNFα; MMP; GAGs; C2C; CPII) at fixed timepoints (post injection hours 0, 8, 24, 72 and 168). The effects of time and treatment on clinical and synovial fluid parameters and the presence of time-treatment interactions were tested using a linear mixed model for repeated measures with horse as a random effect, and time and treatment as fixed effects. Results: The TA treated joints showed significantly higher peak synovial GAG concentrations (Difference in means 283.1875 µg/mL, 95% CI 179.8, 386.6, P < 0.000), and PGE levels (Difference in means 77.8025 pg/mL, 95% CI 21.2, 134.4, P < 0.007) after the first inflammation induction. Significantly lower TP levels were seen with TA treatment after the second induction (Difference in means -7.5 g/L, 95% CI -14.8, -0.20, P < 0.04) . Significantly lower WBCC levels were noted with TA treatment after the first (Difference in means -23.7125 × 10  cells/L, 95% CI -46.7, -0.7, P < 0.04) and second (Difference in means -35.95 × 10  cells/L, 95% CI -59.0, -12.9, P < 0.002) inflammation inductions. Significantly lower general MMP activity was also seen with TA treatment after the second inflammation inductions (Difference in means -51.65 RFU/s, 95% CI -92.4, -10.9, P < 0.01). Conclusions: This experimental study cannot fully reflect natural joint disease. Conclusions: In this model, intra-articular TA seems to have some anti-inflammatory activity (demonstrated by reductions in TP, WBCC and general MMP activity) up to 2 weeks post treatment but not at 4 weeks. This anti-inflammatory effect appeared to outlast a shorter-lived, potentially detrimental effect illustrated by increased synovial GAG and PGE levels after the first induction.
Publication Date: 2020-12-30 PubMed ID: 33280164DOI: 10.1111/evj.13396Google 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.
  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

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.

The research investigated the anti-inflammatory effects of a widely-used joint inflammation treatment known as intra-articular triamcinolone acetonide (TA) using an equine model, concluding that the treatment has some anti-inflammatory activity lasting up to two weeks.

Study Methodology

  • The study is a randomised controlled experimental investigation using a model of repeated joint inflammation across eight horses.
  • Inflammation was induced in all horse subjects for three consecutive cycles that were spaced two weeks apart. The method of inflammation induction involved injecting 0.25 ng of lipopolysaccharide into both middle carpal joints of the horses.
  • After the first round of inflammation induction, one joint in each horse was treated with 12 mg of triamcinolone acetonide (TA). The contralateral joint was instead treated with sterile saline, acting as a control.

Evaluation of Treatment Effects

  • The paper presents a detailed analysis of clinical parameters and synovial fluid samples at set timepoints (0, 8, 24, 72, and 168 hours post-injection).
  • Statistical testing was performed on the gathered data to gauge the impacts of time and treatment on the recorded parameters. The statistical model used accounted for repeated measures, treating time and treatment as fixed effects, and the horse as a random effect.

Findings

  • The study informs that joints treated with TA showed a significant increase in peak synovial Glycosaminoglycans (GAG) concentrations and Prostaglandin E (PGE) levels after the first inflammation induction.
  • The TA treatment also resulted in significantly lower Total Protein (TP) levels after the second inflammation induction, and notably lower White Blood Cell Count (WBCC) levels after the first and second inflammation inductions.
  • A significant reduction in Matrix Metalloproteinase (MMP) activity was noted with TA treatment after the second round of inflammation inductions.

Conclusions

  • The research highlights the limitations of the study, noting that the experiment does not fully express natural joint disease.
  • The findings overall suggest that intra-articular TA possesses some anti-inflammatory activity, demonstrated by reductions in TP, WBCC, and general MMP activity. However, this activity only appears to last up to two weeks post-treatment and not up to four weeks.
  • An interesting observation noted by the study is a shorter-lived, potentially harmful effect indicated by the increased synovial GAG and PGE levels after the initial inflammation induction.

Cite This Article

APA
Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ. (2020). Treatment effects of intra-articular triamcinolone acetonide in an equine model of recurrent joint inflammation. Equine Vet J, 53(6), 1277-1286. https://doi.org/10.1111/evj.13396

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 53
Issue: 6
Pages: 1277-1286

Researcher Affiliations

Kearney, Clodagh M
  • UCD School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
Korthagen, Nicoline M
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Plomp, Saskia G M
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Labberté, Margot C
  • UCD School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
de Grauw, Janny C
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
van Weeren, P R
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Brama, Pieter A J
  • UCD School of Veterinary Medicine, University College Dublin, Dublin, Ireland.

MeSH Terms

  • Animals
  • Horse Diseases / drug therapy
  • Horses
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / veterinary
  • Injections, Intra-Articular / veterinary
  • Synovial Fluid
  • Triamcinolone Acetonide / therapeutic use

Grant Funding

  • LLP-22 / Dutch Arthritis Association
  • UCD Foundation
  • UCD WELLCOME Institutional Strategic Support Fund Clinical Primer Scheme

References

This article includes 47 references
  1. Jüni P, Hari R, Rutjes AW, Fischer R, Silletta MG, Reichenbach S. Intra-articular corticosteroid for knee osteoarthritis.. Cochrane Database Syst Rev 2015;28:496.
  2. McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M. Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: A randomized clinical trial.. JAMA 2017;317:1967-75.
  3. Orchard JW. Is there a place for intra-articular corticosteroid injections in the treatment of knee osteoarthritis?. BMJ 2020;368:l6923.
  4. Bellamy N, Campbell J, Welch V, Gee TL, Bourne R, Wells GA. Intraarticular corticosteroid for treatment of osteoarthritis of the knee.. Cochrane Database Syst Rev 2006;21:429.
  5. Wernecke C, Braun HJ, Dragoo JL. The effect of intra-articular corticosteroids on articular cartilage: a systematic review.. Orthop J Sports Med 2015;3:232596711558116.
  6. Dechant JE, Baxter GM, Frisbie DD, Trotter GW, McIlwraith CW. Effects of dosage titration of methylprednisolone acetate and triamcinolone acetonide on interleukin-1-conditioned equine articular cartilage explants in vitro.. Equine Vet J 2003;35:444-50.
  7. Bolt DM, Ishihara A, Weisbrode SE, Bertone AL. Effects of triamcinolone acetonide, sodium hyaluronate, amikacin sulfate, and mepivacaine hydrochloride, alone and in combination, on morphology and matrix composition of lipopolysaccharide-challenged and unchallenged equine articular cartilage explants.. Am J Vet Res 2008;69:861-7.
  8. Frisbie DD, Kawcak CE, Trotter GW, Powers BE, Walton RM, McIlwraith CW. Effects of triamcinolone acetonide on an in vivo equine osteochondral fragment exercise model.. Equine Vet J 1997;29:349-59.
  9. Celeste C, Ionescu M, Robin Poole A, Laverty S. Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid.. J Orthop Res 2005;23:602-10.
  10. Vandeweerd J-M, Zhao Y, Nisolle J-F, Zhang W, Liu Z, Clegg P. Effect of corticosteroids on articular cartilage: have animal studies said everything?. Fundam Clin Pharmacol 2015;29:427-38.
  11. McIlwraith CW. Use of synovial fluid and serum biomarkers in equine bone and joint disease: a review.. Equine Vet J 2005;37:473-82.
  12. Van den Boom R, van de Lest CHA, Bull S, Brama RAJ, Van Weeren PR, Barneveld A. Influence of repeated arthrocentesis and exercise on synovial fluid concentrations of nitric oxide, prostaglandin E2 and glycosaminoglycans in healthy equine joints.. Equine Vet J 2005;37:250-6.
  13. de Grauw JC, van Loon JPAM, van de Lest CHA, Brunott A, Van Weeren PR. In vivo effects of phenylbutazone on inflammation and cartilage-derived biomarkers in equine joints with acute synovitis.. Vet J 2014;201:51-6.
  14. Williams LB, Koenig JB, Black B, Gibson TWG, Sharif S, Koch TG. Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self-limiting inflammation when evaluated in an LPS induced synovitis model.. Equine Vet J 2015;48:619-25.
  15. Sladek S, Kearney C, Crean D, Brama PAJ, Tajber L, Fawcett K. Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation.. Drug Deliv and Transl Res 2018;8:1421-35.
  16. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.. Nat Rev Rheumatol 2010;6:625-35.
  17. Punzi L, Galozzi P, Luisetto R, Favero M, Ramonda R, Oliviero F. Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation.. RMD Open 2016;2:e000279.
  18. Cokelaere SM, Plomp SGM, de Boef E, de Leeuw M, Bool S, van de Lest CHA. Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model.. Eur J Pharm Biopharm 2018;128:327-36.
  19. Owens JG, Kamerling SG, Stanton SR, Keowen ML, Prescott-Mathews JS. Effects of pretreatment with ketoprofen and phenylbutazone on experimentally induced synovitis in horses.. Am J Vet Res 1996;57:866-74.
  20. de Grauw JC, van de Lest CHA, van Weeren PR. A targeted lipidomics approach to the study of eicosanoid release in synovial joints.. Arthritis Res Ther 2011;13:R123.
  21. Grauw JC, Lest CHA, Brama P, Rambags BPB, Weeren PR. In vivo effects of meloxicam on inflammatory mediators, MMP activity and cartilage biomarkers in equine joints with acute synovitis.. Equine Vet J 2009;41:693-9.
  22. McIlwraith CW, Lattermann C. Intra-articular corticosteroids for knee pain-what have we learned from the equine athlete and current best practice.. J Knee Surg 2019;32:9-25.
  23. Labens R, Voute LC, Mellor DJ. Retrospective study of the effect of intra-articular treatment of osteoarthritis of the distal tarsal joints in 51 horses.. Veterinary Record 2007;161:611-6.
  24. Ferris DJ, Frisbie DD, McIlwraith CW, Kawcak CE. Current joint therapy usage in equine practice: a survey of veterinarians 2009.. Equine Vet J 2011;43:530-5.
  25. Syed HM, Green L, Bianski B, Jobe CM, Wongworawat MD. Bupivacaine and triamcinolone may be toxic to human chondrocytes: A pilot study.. Clin Orthop Relat Res 2011;469:2941-7.
  26. Dragoo JL, Danial CM, Braun HJ, Pouliot MA, Kim HJ. The chondrotoxicity of single-dose corticosteroids.. Knee Surg Sports Traumatol Arthrosc 2012;20:1809-14.
  27. Trahan RA, Byron CR, Dahlgren LA, Pleasant RS, Werre SR. In vitro effects of three equimolar concentrations of methylprednisolone acetate, triamcinolone acetonide, and isoflupredone acetate on equine articular tissue cocultures in an inflammatory environment.. Am J Vet Res 2018;79:933-40.
  28. de Grauw JC, Van de Lest CH. Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study.. Arthritis Res Ther 2009;11:R35.
  29. Palmer JL, Bertone AL. Experimentally-induced synovitis as a model for acute synovitis in the horse.. Equine Vet J 1994;26:492-5.
  30. Kay AT, Bolt DM, Ishihara A, Rajala-Schultz PJ, Bertone AL. Anti-inflammatory and analgesic effects of intra-articular injection of triamcinolone acetonide, mepivacaine hydrochloride, or both on lipopolysaccharide-induced lameness in horses.. Am J Vet Res 2008;69:1646-54.
  31. Ekstrand C, Bondesson U, Giving E, Hedeland M, Ingvast-Larsson C, Jacobsen S. Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis.. Acta Vet Scand 2019;61:1-17.
  32. Palmer JL, Bertone AL, Malemud CJ, Mansour J. Biochemical and biomechanical alterations in equine articular cartilage following an experimentally-induced synovitis.. Osteoarthritis Cartilage 1996;4:127-37.
  33. Orth P, Zurakowski D, Alini M, Cucchiarini M, Madry H. Reduction of sample size requirements by bilateral versus unilateral research designs in animal models for cartilage.. Tissue Eng 2013;19:885-91.
  34. Dyson S. Can lameness be graded reliably?. Equine Vet J 2011;43:379-82.
  35. Henriksen M, Christensen R, Klokker L, Bartholdy C, Bandak E, Ellegaard K. Evaluation of the benefit of corticosteroid injection before exercise therapy in patients with osteoarthritis of the knee: a randomized clinical trial.. JAMA Intern Med 2015;175:923-30.
  36. Garvican ER, Vaughan-Thomas A, Redmond C, Gabriel N, Clegg PD. MMP-mediated collagen breakdown induced by activated protein C in equine cartilage is reduced by corticosteroids.. J Orthop Res 2010;28:370-8.
  37. Frisbie DD, Al-Sobayil F, Billinghurst RC, Kawcak CE, McIlwraith CW. Changes in synovial fluid and serum biomarkers with exercise and early osteoarthritis in horses.. Osteoarthritis Cartilage 2008;16:1196-204.
  38. Kirker-Head CA, Chandna VK, Agarwal RK, Morris EA, Tidwell A, O'Callaghan MW. Concentrations of substance P and prostaglandin E 2in synovial fluid of normal and abnormal joints of horses.. Am J Vet Res 2000;61:714-8.
  39. Bertone AL, Palmer JL, Jones J. Synovial fluid cytokines and eicosanoids as markers of joint disease in horses.. Vet Surg 2001;30:528-38.
  40. Frisbie DD, Kawcak CE, Baxter GM, Trotter GW, Powers BE, Lassen ED. Effects of 6alpha-methylprednisolone acetate on an equine osteochondral fragment exercise model.. Am J Vet Res 1998;59:1619-28.
  41. Neuenschwander HM, Moreira JJ, Vendruscolo CP, Fülber J, Seidel SRT, Michelacci YM. Hyaluronic acid has chondroprotective and joint-preserving effects on LPS-induced synovitis in horses.. J Vet Sci 2019;20:e67.
  42. Mangal D, Uboh CE, Soma LR, Liu Y. Inhibitory effect of triamcinolone acetonide on synthesis of inflammatory mediators in the equine.. Eur J Pharmacol 2014;736:1-9.
  43. Ronchetti S, Migliorati G, Bruscoli S, Riccardi C. Defining the role of glucocorticoids in inflammation.. Clin. Sci. 2018;132:1529-43.
  44. Avunduk C, Eastwood GL, Polakowski N, Burstein S. Hydrocortisone has a biphasic effect on rat gastric mucosal prostaglandin generation in vivo: Inhibition at low doses, stimulation at high doses.. Prostaglandins Leukot Essent Fatty Acids 1992;45:329-32.
  45. 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;45:715-20.
  46. van Loon JPAM, de Grauw JC, Brunott A, Weerts EAWS, Van Weeren PR. Upregulation of articular synovial membrane μ-opioid-like receptors in an acute equine synovitis model.. Vet J 2013;196:40-6.
  47. Todhunter RJ, Fubini SL, Vernier-Singer M, Wootton JA, Lust G, Freeman KP. Acute synovitis and intra-articular methylprednisolone acetate in ponies.. Osteoarthritis Cartilage 1998;6:94-105.

Citations

This article has been cited 4 times.
  1. Kearney CM, Khatab S, van Buul GM, Plomp SGM, Korthagen NM, Labberté MC, Goodrich LR, Kisiday JD, Van Weeren PR, van Osch GJVM, Brama PAJ. Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation. Front Vet Sci 2022;9:907616.
    doi: 10.3389/fvets.2022.907616pubmed: 35812845google scholar: lookup
  2. 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
  3. Scheike AS, Plomp S, Fugazzola MC, Meurot C, Berenbaum F, van Weeren PR, Tryfonidou MA, von Hegedus JH. The Anti-Inflammatory Effects of Liraglutide in Equine Inflammatory Joint Models. J Orthop Res 2025 May;43(5):893-903.
    doi: 10.1002/jor.26050pubmed: 39904754google scholar: lookup
  4. Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ. A Translational Model for Repeated Episodes of Joint Inflammation: Welfare, Clinical and Synovial Fluid Biomarker Assessment. Animals (Basel) 2023 Oct 12;13(20).
    doi: 10.3390/ani13203190pubmed: 37893914google scholar: lookup