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Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses—a preliminary investigation

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  • To determine effects of intraarticularly administered tiludronate on articular cartilage in vivo, eight healthy horses were injected once with tiludronate (low dose tiludronate [LDT] 0.017 mg, n = 4; high dose tiludronate [HDT] 50 mg, n = 4) into one middle carpal joint and with saline into the contralateral joint. Arthrocentesis of both middle carpal joints was performed pre-treatment, and 10 min, 24 h, 48 h, 7 and 14 days after treatment. Synovial nucleated cell counts and total solids, tiludronate, sulfated glycosaminoglycan (sGAG), chondroitin sulfate 846 epitope (CS-846, a measure of aggrecan synthesis), and collagen type II cleavage neoepitope (C2C) concentrations were determined. Histologic analysis of joint tissues and sGAG quantitation in cartilage was performed at 14 days in HDT horses. Data were analyzed by repeated measures non-parametric ANOVA and Wilcoxon signed-rank test. High dose tiludronate administration produced synovial fluid tiludronate concentrations of 2,677,500 ng/mL, exceeding concentrations that were safe for cartilage in vitro, and LDT administration produced synovial fluid concentrations of 1,353 ng/mL, remaining below concentrations considered potentially detrimental to cartilage. With HDT, synovial fluid total solids concentration was higher at 24 h and 7 days and sGAG concentration was higher at 48 h, compared to control joints. Synovial fluid CS-846 concentration was increased over pre-treatment values in HDT control but not in HDT treated joints at 24 and 48 h. All joints (HDT and LDT control and treated) showed a temporary decrease in synovial fluid C2C concentration, compared to pre-treatment values. Histologic features of articular cartilage and synovial membrane did not differ between HDT treated and control joints. High dose tiludronate treatment caused a transient increase in synovial total solids and temporarily increased proteoglycan degradation in cartilage. Although clinical significance of these changes are questionable, as they did not result in articular cartilage damage, further investigation of the safety of intraarticular HDT in a larger number of horses is warranted.
  • This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by PeerJ. The published article can be found at: https://peerj.com/.
  • Keywords: Cartilage, Joint injection, Bisphosphonate, Glycosaminoglycans, Horse, Rheumatology, Drugs and Devices, Tiludronate, Veterinary Medicine
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  • Duesterdieck-Zellmer KF, Moneta L, Ott JF, Larson MK, Gorman EM, Hunter B, Löhr CV, Payton ME, Morré JT, Maier CS. 2014. Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses—a preliminary investigation. PeerJ 2:e534 https://doi.org/10.7717/peerj.534
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  • Funding for this study was provided by the Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, and the Knapp Friesian Foundation, Inc., in addition to the Merial Scholars Program and the Department of Clinical Sciences Summer Research Program of Oregon State University (L Moneta). Oregon State University’s mass spectrometry facility is in part supported by the National Institute of Environmental Health Sciences (Grant Number P30ES000210).
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