• 1. Ackerman N, Johnson JH, Dorn CR, et al. Navicular disease in the horse: risk factors, radiographic changes, and response to therapy. J Am Vet Med Assoc 1977; 170: 183187.

    • Search Google Scholar
    • Export Citation
  • 2. Dabareiner RM, Cohen ND, Carter GK, et al. Lameness and poor performance in horses used for team roping: 118 cases (2000–2003). J Am Vet Med Assoc 2005; 226: 16941699.

    • Search Google Scholar
    • Export Citation
  • 3. Dabareiner RM, Cohen ND, Carter GK, et al. Musculoskeletal problems associated with lameness and poor performance among horses used for barrel racing: 118 cases (2000–2003). J Am Vet Med Assoc 2005; 227: 16461650.

    • Search Google Scholar
    • Export Citation
  • 4. Waguespack RW, Hanson RR. Navicular syndrome in equine patients: anatomy, causes and diagnosis. Compend Contin Educ Vet 2010; 32: E7.

  • 5. Waguespack RW, Hanson RR. Treating navicular syndrome in equine patients. Compend Contin Educ Vet 2011; 33: E2.

  • 6. Gutierrez-Nibeyro SD, White NA, Werpy NM. Outcome of medical treatment for horses with foot pain: 56 cases. Equine Vet J 2010; 42: 680685.

    • Search Google Scholar
    • Export Citation
  • 7. Chappard D, Minaire P, Privat C, et al. Effects of tiludronate on bone loss in paraplegic patients. J Bone Miner Res 1995; 10: 112118.

    • Search Google Scholar
    • Export Citation
  • 8. Fraser WD, Stamp TC, Creek RA, et al. A double blind, multicentre, placebo-controlled study of tiludronate in Paget's disease of bone. Postgrad Med J 1997; 73: 496502.

    • Search Google Scholar
    • Export Citation
  • 9. Woo T, Adachi JD. Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis. Best Pract Res Clin Rheumatol 2001; 15: 469481.

    • Search Google Scholar
    • Export Citation
  • 10. Masarachia P, Weinreb M, Balena R, et al. Comparison of the distribution of 3H-alendronate and 3H-etidronate in rat and mouse bones. Bone 1996; 19: 281290.

    • Search Google Scholar
    • Export Citation
  • 11. Gatti D, Adami S. New bisphosphonates in the treatment of bone diseases. Drugs Aging 1999; 15: 285296.

  • 12. Denoix J-M, Thibaud D, Ricco 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.

    • Search Google Scholar
    • Export Citation
  • 13. Coudry V, Thibaud D, Ricco B, et al. Efficacy of tiludronate in the treatment of horse with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column. Am J Vet Res 2007; 48: 329337.

    • Search Google Scholar
    • Export Citation
  • 14. Gouch M, Thibaud D, Smith K. Tiludronate infusion in the treatment of bone spavin: a double blinded placebo-controlled trial. Equine Vet J 2010; 42: 381387.

    • Search Google Scholar
    • Export Citation
  • 15. Carpenter RS. How to treat dorsal metacarpal disease with regional tiludronate and extracorporeal shock wave therapies in Thoroughbred racehorses, in Proceedings. Annu Conv Am Assoc Equine Pract 2012; 58: 546549.

    • Search Google Scholar
    • Export Citation
  • 16. Hunter BG, Duesterdieck-Zellmer KF, Larson MK. Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses. Peer J 2015; 3: E889.

    • Search Google Scholar
    • Export Citation
  • 17. Rubio-Martinez LM, Cruz AM. Antimicrobial regional limb perfusion in horses. J Am Vet Med Assoc 2006; 228: 706712.

  • 18. Keegan KG, Wilson DA, Wilson DJ, et al. Evaluation of mild lameness in horses trotting on a treadmill by clinicians and interns or residents and correlation of their assessments with kinematic gait analysis. Am J Vet Res 1998; 59: 13701377.

    • Search Google Scholar
    • Export Citation
  • 19. Fuller CJ, Bladon BM, Driver AJ, et al. The intra- and inter-assessor reliability of measurement of functional outcome by lameness scoring in horses. Vet J 2006; 171: 281286.

    • Search Google Scholar
    • Export Citation
  • 20. Hewetson M, Christley RM, Hunt ID, et al. Investigations of the reliability of observational gait analysis for the assessment of lameness in horses. Vet Rec 2006; 158: 852857.

    • Search Google Scholar
    • Export Citation
  • 21. Waxman AS, Robinson DA, Evans RB, et al. Relationship between objective and subjective assessment of limb function in normal dogs with an experimentally induced lameness. Vet Surg 2008; 37: 241246.

    • Search Google Scholar
    • Export Citation
  • 22. Keegan KG, Dent EV, Wilson DA, et al. Repeatability of subjective evaluation of lameness in horses. Equine Vet J 2010; 42: 9297.

  • 23. Merkens HW, Schamhardt HC. Evaluation of equine locomotion during different degrees of experimentally induced lameness. I: lameness model and quantification of ground reactive force patterns on the limbs. Equine Vet J Suppl 1988;(6):99106.

    • Search Google Scholar
    • Export Citation
  • 24. Merkens HW, Schamhardt HC. Evaluation of equine locomotion during different degrees of experimentally induced lameness. II: distribution of ground reactive force patterns of the concurrently loaded limbs. Equine Vet J Suppl 1988;(6):107112.

    • Search Google Scholar
    • Export Citation
  • 25. Schoonover MJ, Jann HW, Blaik MA. Quantitative comparison of three commonly used treatments for navicular syndrome in horses. Am J Vet Res 2005; 66: 12471251.

    • Search Google Scholar
    • Export Citation
  • 26. Erkert RS, MacAlister CG, Payton ME, et al. Use of force plate analysis to compare the analgesic effects of intravenous administration of phenylbutazone and flunixin meglumine in horses with navicular syndrome. Am J Vet Res 2005; 66: 284288.

    • Search Google Scholar
    • Export Citation
  • 27. Symonds KD, MacAllister CG, Erkert RS, et al. Use of force plate to assess the analgesic effects of etodolac in horses with navicular syndrome. Am J Vet Res 2006; 67: 557561.

    • Search Google Scholar
    • Export Citation
  • 28. Ishihara A, Bertone AL, Rajala-Schultz PJ. Association between subjective lameness grade and kinetic gait parameters in horses with experimentally induced forelimb lameness. Am J Vet Res 2005; 66: 18051815.

    • Search Google Scholar
    • Export Citation
  • 29. Keegan KG, MacAllister CG, Wilson DA, et al. Comparison of an inertial sensor system with a stationary force plate for evaluation of horses with bilateral forelimb lameness. Am J Vet Res 2012; 73: 368374.

    • Search Google Scholar
    • Export Citation
  • 30. AAEP. Definition and classification of lameness. In: Guide for veterinary service and judging of equestrian events. 4th ed. Lexington, Ky: AAEP, 1991;19.

    • Search Google Scholar
    • Export Citation
  • 31. Dik KJ, van den Broek J. Role of navicular bone shape in the pathogenesis of navicular disease: a radiological study. Equine Vet J 1995; 27: 390393.

    • Search Google Scholar
    • Export Citation
  • 32. Pool RR, Meagher DM, Stover SM. Pathophysiology of navicular syndrome. Vet Clin North Am Equine Pract 1989; 5: 109129.

  • 33. Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 2008; 83: 10321045.

    • Search Google Scholar
    • Export Citation
  • 34. Lasseter KC, Porras AG, Denker A, et al. Pharmacokinetic considerations in determining the terminal elimination half-lives of bisphosphonates. Clin Drug Investig 2005; 25: 107114.

    • Search Google Scholar
    • Export Citation
  • 35. Ostblom L, Lund C, Melsen F. Histological study of navicular bone disease. Equine Vet J 1982; 14: 199202.

  • 36. Ostblom L, Lund C, Melsen F. Navicular bone disease: a comparative histomorphometric study. Equine Vet J 1989; 21: 431433.

  • 37. Jee W. Integrated bone tissue physiology: anatomy and physiology. In: Cowin SC, ed. Bone mechanics handbook. 2nd ed. Boca Raton, Fla: CRC Press, 2001;1.11.68.

    • Search Google Scholar
    • Export Citation
  • 38. Mönkkönen J, Similä J, Rogers MJ. Effects of tiludronate and ibandronate on the secretion of proinflammatory cytokines and nitric oxide from macrophages in vitro. Life Sci 1998; 62:PL95PL102.

    • Search Google Scholar
    • Export Citation
  • 39. Yoshida M, Tokuda H, Ishisaki A, et al. Tiludronate inhibits prostaglandin F2a-induced vascular endothelial growth factor synthesis in osteoblasts. Mol Cell Endocrinol 2005; 239: 5966.

    • Search Google Scholar
    • Export Citation
  • 40. Nakaya H, Osawa G, Iwasaki N, et al. Effects of bisphosphonates on matrix metalloproteinase enzymes in human periodontal ligament cells. J Periodontol 2000; 71: 11581166.

    • Search Google Scholar
    • Export Citation
  • 41. Blunden A, Dyson S, Murray R, et al. Histopathology in horses with chronic palmar foot pain and age-matched controls. Part 1: navicular bone and related structures. Equine Vet J 2006; 38: 1522.

    • Search Google Scholar
    • Export Citation
  • 42. Dyson SJ. Navicular disease and other soft tissue causes of palmar foot pain. In: Ross MW, Dyson SJ, eds. Diagnosis and management of lameness in the horse. St Louis: Saunders, 2003;286299.

    • Search Google Scholar
    • Export Citation
  • 43. Widmer WR, Buckwalter KA, Fessler JF, et al. Use of radiography, computed tomography and magnetic resonance imaging for evaluation of navicular syndrome in the horse. Vet Radiol Ultrasound 2000; 41: 108116.

    • Search Google Scholar
    • Export Citation
  • 44. Sampson SN, Schneider RK, Gavin PR, et al. Magnetic resonance imaging findings in horses with recent onset navicular syndrome but without radiographic abnormalities. Vet Radiol Ultrasound 2009; 50: 339346.

    • Search Google Scholar
    • Export Citation

Quantitative assessment of two methods of tiludronate administration for the treatment of lameness caused by navicular syndrome in horses

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  • 1 Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74074.
  • | 2 Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74074.
  • | 3 Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74074.
  • | 4 Department of Statistics, College of Arts and Sciences, Oklahoma State University, Stillwater, OK 74074.
  • | 5 Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74074.

Abstract

OBJECTIVE To determine effects of 2 tiludronate administration protocols on measures of lameness in horses with navicular syndrome (NS).

ANIMALS 12 horses with bilateral forelimb NS.

PROCEDURES Horses were randomly assigned to receive tiludronate (1 mg/kg), diluted in 5 L of isotonic electrolyte solution and delivered through a jugular vein catheter (systemic treatment group; n = 6), or tiludronate (0.1 mg/kg), diluted with saline (0.9% NaCl) solution to a total volume of 35 mL and delivered into the lateral digital vein of each forelimb with an IV regional limb perfusion (IVRLP) technique (IVRLP group; 6). Mean peak vertical ground reaction force (pVGRF) measured with a stationary force plate and subjective lameness scores (SLSs) were recorded before (day −1) and at predetermined time points after tiludronate administration on day 0. Mean pVGRFs (standardized as percentage body weight of force) and mean SLSs for the most lame forelimb and for both forelimbs of horses in each group were compared with day −1 values to determine treatment effect.

RESULTS Mean pVGRF for both forelimbs and for the most lame forelimbs of systemically treated horses were significantly increased on days 120 and 200, compared with day −1 results. No significant difference in mean pVGRF was observed for IVRLP-treated horses. The SLSs were not improved at any time point following systemic treatment and were improved only on day 120 following IVRLP.

CONCLUSIONS AND CLINICAL RELEVANCE Tiludronate (1 mg/kg, IV) as a single systemic treatment appeared to be beneficial for horses with NS, but no horses were judged as sound during the study period. Additional research on IVRLP with tiludronate is needed before this method can be recommended. (Am J Vet Res 2016;77:167–173)

Abstract

OBJECTIVE To determine effects of 2 tiludronate administration protocols on measures of lameness in horses with navicular syndrome (NS).

ANIMALS 12 horses with bilateral forelimb NS.

PROCEDURES Horses were randomly assigned to receive tiludronate (1 mg/kg), diluted in 5 L of isotonic electrolyte solution and delivered through a jugular vein catheter (systemic treatment group; n = 6), or tiludronate (0.1 mg/kg), diluted with saline (0.9% NaCl) solution to a total volume of 35 mL and delivered into the lateral digital vein of each forelimb with an IV regional limb perfusion (IVRLP) technique (IVRLP group; 6). Mean peak vertical ground reaction force (pVGRF) measured with a stationary force plate and subjective lameness scores (SLSs) were recorded before (day −1) and at predetermined time points after tiludronate administration on day 0. Mean pVGRFs (standardized as percentage body weight of force) and mean SLSs for the most lame forelimb and for both forelimbs of horses in each group were compared with day −1 values to determine treatment effect.

RESULTS Mean pVGRF for both forelimbs and for the most lame forelimbs of systemically treated horses were significantly increased on days 120 and 200, compared with day −1 results. No significant difference in mean pVGRF was observed for IVRLP-treated horses. The SLSs were not improved at any time point following systemic treatment and were improved only on day 120 following IVRLP.

CONCLUSIONS AND CLINICAL RELEVANCE Tiludronate (1 mg/kg, IV) as a single systemic treatment appeared to be beneficial for horses with NS, but no horses were judged as sound during the study period. Additional research on IVRLP with tiludronate is needed before this method can be recommended. (Am J Vet Res 2016;77:167–173)

Contributor Notes

Address correspondence to Dr. Whitfield (chasetw@okstate.edu).