• 1.

    McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis. Bone Joint Res 2012;1:297309.

  • 2.

    Riggs CM. Osteochondral injury and joint disease in the athletic horse. Equine Vet Educ 2006;18:100112.

  • 3.

    Anderson DD, Chubinskaya S, Guilak F, et al. Post traumatic osteoarthritis: improved understanding and opportunities for early intervention. J Orthop Res 2011;29:802809.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Brommer H, van Weeren PR, Brama PAJ, et al. Quantification and age-related distribution of the articular cartilage degeneration in the equine fetlock joint. Equine Vet J 2003;35:697701.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Whittaker JL, Woodhouse LJ, Nettel-Aguirre A, et al. Outcomes associated with early post traumatic osteoarthritis and other negative health consequences 3–10 years following knee joint injury in youth sport. Osteoarthritis Cartilage 2015;23:11221129.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Bertuglia A, Pagliara E, Grego E, et al. Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standarbred racehorses over five years of racing career. BMC Vet Res 2016;12:246.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Frisbie DD, Kawcak CE, McIlwraith CW, et al. Evaluation of polysulfated glycosaminoglycan or sodium hyaluronan administered intra-articularly for treatment of horses with experimentally induced osteoarthritis. Am J Vet Res 2009;70:203209.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Ferris DJ, Frisbie DD, McIlwraith WC, et al. Current joint therapy usage in equine practice: a survey of veterinarians in 2009. Equine Vet J 2011;43:530535.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Machado TSL, Massoco CO, Silva LC, et al. Effect of blood-derived products and sodium hyaluronate on equine synovial fluid cells and on synovial fluid from osteochondrotic joints of horses after arthroscopy and administration of treatment. Am J Vet Res 2019;80:646656.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Céleste C, Ionescu M, Poole RA, et al. Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid. J Orthop Res 2005;23:602610.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Wernecke C, Braun HJ, Dragoo JL, et al. The effect of intraarticular corticosteroids on articular cartilage. A systematic review. Orthop J Sports Med 2015;3:2325967115581163.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Martel-Pellettier J, Kwan Tat S, Pellettier J-P. Effect of chondroitin sulphate in the pathophysiology of the osteoarthritic joint: a narrative review. Osteoarthritis Cartilage 2010;18:S7S11.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Frisbie DD, McIlwraith CW, Kawcak CE, et al. Evaluation of intra-articular hyaluronan, sodium chondroitin sulphate and N-acetyl-D-glucosamine combination versus saline (0.9% NaCl) for osteoarthritis using an equine model. Vet J 2013;197:824829.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Watson Levings RS, Smith AD, Broome TA, et al. Self-complementary adeno-associated virus-mediated interleukin-1 receptor antagonist gene delivery for the treatment of osteo-arthritis: test of efficacy in an equine model. Hum Gene Ther Clin Dev 2018;29:101112.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Frisbie DD, Kawcak CE, Werpy NM, et al. Clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum in horses with experimentally induced osteoarthritis. Am J Vet Res 2007;68:290296.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Frisbie DD, Ghivizzani SC, Robbins PD, et al. Treatment of experimental equine osteoarthritis by in vivo delivery of equine interleukin-1 receptor antagonist gene. Gene Ther 2002;9:1220.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    McIlwraith CW. Traumatic arthritis and posttraumatic osteo-arthritis in the horse. In: McIlwraith CW, Frisbie DD, Kawcak CE, et al., eds. Joint disease in the horse. 2nd ed. St Louis: Elsevier, 2016;3348.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Denoix JM, Thibaud D, Riccio B. Tiludronate as a new therapeutic agent in the treatment of navicular disease: a double-blind placebo-controlled clinical trial. Equine Vet J 2003;35:407413.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Gough MR, Thibaud D, Smith RKW. Tiludronate infusion in the treatment of bone spavin: a double blind placebo-controlled trial. Equine Vet J 2010;42:381387.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Coudry V, Thibaud D, Riccio B, et al. Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column. Am J Vet Res 2007;68:329337.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Duesterdieck-Zellmer KF, Moneta L, Ott JF, et al. Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses—a preliminary investigation. PeerJ 2014;2:e534.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    McLellan J. Science-in-brief: bisphosphonate use in the race-horse: safe or unsafe? Equine Vet J 2017;49:404407.

  • 23.

    Rosen HN, Moses AC, Garber J, et al. Serum CTX: a new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int 2000;66:100103.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Delguste C, Amory H, Doucet M, et al. Pharmacological effects of tiludronate in horses after long-term immobilization. Bone 2007;41:414421.

  • 25.

    Saviola G, Abdi-Ali L, Comini L, et al. Use of clodronate in the management of osteoarthritis: an update. J Biol Regul Homeost Agents 2019;33:13151320.

    • Search Google Scholar
    • Export Citation
  • 26.

    Xing RL, Zhao LR, Wang PM. Bisphosphonates therapy for osteoarthritis: a meta-analysis of randomized controlled trials. Springerplus 2016;5:1704.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Delguste C, Amory H, Guyonnet J, et al. Comparative pharmacokinetics of two intravenous administration regimens of tiludro-nate in healthy adult horses and effects on the bone resorption marker CTX-1. J Vet Pharmacol Ther 2008;31:108116.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    American Association of Equine Practitioners. Lameness exams: evaluating the lame horse. Available at: aaep.org/horsehealth/lameness-exams-evaluating-lame-horse. Accessed Feb 17, 2021.

    • Search Google Scholar
    • Export Citation
  • 29.

    Frisbie DD, Al-Sobayil F, Billinghurst RC, et al. Changes in synovial and serum biomarkers with exercise and early osteoarthritis in horses. Osteoarthritis Cartilage 2008;16:11961204.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    de Grauw JC, van de Lest CHA, Van Weeren PR. Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experiment study. Arthritis Res Ther 2009;11:R35.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Lohmander LS, Atley LM, Pietka TA, et al. The release of crosslinked peptides from type II collagen into human syno-vial fluid is increased soon after joint injury and in osteoarthritis. Arthritis Rheum 2003;11:31303139.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    McIlwraith CW. Use of synovial fluid and serum biomarkers in equine bone and joint disease: a review. Equine Vet J 2005;37:473482.

  • 33.

    Carstanjen B, Hoyle NR, Gabriel A, et al. Evaluation of plasma carboxy-terminal cross-linking telopeptide of type I collagen concentration in horses. Am J Vet Res 2004;65:104109.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Ma T-W, Li Y, Wang G-Y, Li X-R et al. Changes in synovial fluid biomarkers after experimental equine osteoarthritis. J Vet Res 2017;61:503508.

  • 35.

    Faul F, Erdfelder E, Buchner A, et al. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009;41:11491160.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Mitchell A, Wright G, Sampson SN, et al. Clodronate improves lameness in horses without changing bone turnover markers. Equine Vet J 2019;53:356363.

  • 37.

    Crevier-Denoix N, Audigié F, Emond A-L, et al. Effect of track surface firmness on the development of musculoskeletal injuries in French Trotters during four months of harness race training. Am J Vet Res 2017;78:12931304.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Moreau M, Rialland P, Pelletier JP, et al. Tiludronate treatment improves structural changes and symptoms of osteo-arthritis in the canine anterior cruciate ligament model. Arthritis Res Ther 2011;13:R98.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Fan TM, De Lorimier LP, Charney SC, et al. Evaluation of intravenous pamidronate administration in 33 cancer-bearing dogs with primary or secondary bone involvement. J Vet Intern Med 2005;19:7480.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40.

    Han P-F, Lei W, Zhi-Qing D, et al. Contribution of IL-1β, 6, and TNF-α to the form of post-traumatic osteoarthritis induced by “idealized” anterior cruciate ligament reconstruction in a porcine model. Int Immunopharmacol 2018;65:212220.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41.

    Maninchedda U, Lepage OM, Gangl M, et al. Development of an equine groove model to induce metacarpophalangeal osteoarthritis: a pilot study on 6 horses. PLoS One 2015;10:e0115089.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Cleary OB, Trumble TN, Merritt KA, et al. Effect of exercise and osteochondral injury on synovial fluid and serum concentrations of carboxy-terminal telopeptide fragments of type II collagen in racehorses. Am J Vet Res 2010;71:3340.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    Boyce MK, Trumble TN, Carlson CS, et al. Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury. Osteoarthritis Cartilage 2013;21:746755.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44.

    Sakao K, Takahashi KA, Arai Y, et al. Osteoblasts derived from osteophytes produce interleukin-6, interleukin-8, and matrix metalloproteinase-13 in osteoarthritis. J Bone Miner Metab 2009;27:412423.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45.

    Daghestani HN, Kraus VB. Inflammatory biomarkers in osteoarthritis. Osteoarthritis Cartilage 2015;23:18901896.

  • 46.

    Poole AR, Kobayashi M, Yasuda T, et al. Type II collagen degradation and its regulation in articular cartilage in osteoarthritis. Ann Rheum Dis 2002;61(suppl 2):7881.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47.

    Frisbie DD, McIlwraith CW, De Grauw JC. Synovial fluid and serum biomarkers. In: McIlwraith CW, Frisbie DD, Kawcak CE, et al., eds. Joint disease in the horse. 2nd ed. St Louis: Elsevier, 2016;179191.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48.

    Frisbie DD, Kawcak CE, Trotter GW, et al. The effects of triamcinolone acetate on an in vivo equine osteochondral fragment exercise model. Equine Vet J 1997;29:349359.

    • Crossref
    • Search Google Scholar
    • Export Citation

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Effect of intravenous tiludronate disodium administration on the radiographic progression of osteoarthritis of the fetlock joint in Standardbred racehorses

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  • 1 From the Department of Veterinary Science, University of Turin, Grugliasco 10095, Italy
  • | 2 Department of Surgery, Orthopaedics and Ophthalmology Clinic, University of Zagreb, Zagreb 10000, Croatia
  • | 3 Department of Veterinary Medical Sciences, University of Bologna, Bologna 40126, Italy (Spinella).

Abstract

OBJECTIVE

To compare the effects of tiludronate disodium and 3 other medical treatments on clinical and radiographic findings and biomarkers of disease progression in horses with osteoarthritis of the fetlock joint.

ANIMALS

100 Standardbred racehorses with spontaneous traumatic injury of the fet-lock joint.

PROCEDURES

Horses were retrospectively grouped by whether they received tiludronate IV or triamcinolone acetonide and hyaluronan, polysulfated glycosaminoglycan, or interleukin-1 receptor antagonist protein intra-articularly. Data were collected on clinical, radiographic, and ultrasonographic findings and results for serum and synovial samples obtained before and 6 months after treatment. Lameness score, joint flexion test response, radiographic score, serum concentrations of tumor necrosis factor-α and carboxy-terminal telopeptides of collagen types I and II (CTX-I and II, respectively), and synovial fluid concentrations of interleukin-1β, prostaglandin E2, and CTX-II were compared among treatments.

RESULTS

All treatments resulted in a significant improvement in lameness score and joint flexion test response at 6 months. In horses that received triamcino-lone acetonide and hyaluronan, synovial fluid interleukin-1β, prostaglandin E2, and CTX-II concentrations decreased after treatment, suggesting this treatment inhibited progression of hyaline cartilage degeneration and inflammatory processes. Horses that received tiludronate were the only group that had a decrease in radiographic score and serum CTX-I concentration after treatment, supporting the effect of tiludronate on bone metabolism. Tiludronate treatment was also followed by increases in serum and synovial fluid concentrations of CTX-II, a marker of cartilage damage.

CONCLUSIONS AND CLINICAL RELEVANCE

Tiludronate appeared to inhibit the radiographic progression of osteoarthritis in high-motion joints of racehorses at 6 months after treatment by inhibiting subchondral bone remodeling. Whether this effect was associated with a worsening of progressive cartilage damage remains to be ascertained.

Abstract

OBJECTIVE

To compare the effects of tiludronate disodium and 3 other medical treatments on clinical and radiographic findings and biomarkers of disease progression in horses with osteoarthritis of the fetlock joint.

ANIMALS

100 Standardbred racehorses with spontaneous traumatic injury of the fet-lock joint.

PROCEDURES

Horses were retrospectively grouped by whether they received tiludronate IV or triamcinolone acetonide and hyaluronan, polysulfated glycosaminoglycan, or interleukin-1 receptor antagonist protein intra-articularly. Data were collected on clinical, radiographic, and ultrasonographic findings and results for serum and synovial samples obtained before and 6 months after treatment. Lameness score, joint flexion test response, radiographic score, serum concentrations of tumor necrosis factor-α and carboxy-terminal telopeptides of collagen types I and II (CTX-I and II, respectively), and synovial fluid concentrations of interleukin-1β, prostaglandin E2, and CTX-II were compared among treatments.

RESULTS

All treatments resulted in a significant improvement in lameness score and joint flexion test response at 6 months. In horses that received triamcino-lone acetonide and hyaluronan, synovial fluid interleukin-1β, prostaglandin E2, and CTX-II concentrations decreased after treatment, suggesting this treatment inhibited progression of hyaline cartilage degeneration and inflammatory processes. Horses that received tiludronate were the only group that had a decrease in radiographic score and serum CTX-I concentration after treatment, supporting the effect of tiludronate on bone metabolism. Tiludronate treatment was also followed by increases in serum and synovial fluid concentrations of CTX-II, a marker of cartilage damage.

CONCLUSIONS AND CLINICAL RELEVANCE

Tiludronate appeared to inhibit the radiographic progression of osteoarthritis in high-motion joints of racehorses at 6 months after treatment by inhibiting subchondral bone remodeling. Whether this effect was associated with a worsening of progressive cartilage damage remains to be ascertained.

Contributor Notes

Address correspondence to Dr. Bertuglia (andrea.bertuglia@unito.it).