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Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses

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Title Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses
Names Hunter, Barbara G. (creator)
Duesterdieck-Zellmer, Katja F. (creator)
Larson, Maureen K. (creator)
Date Issued 2015-04-28 (iso8601)
Note 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/.
Abstract Anecdotal accounts of tiludronate administration via intravenous regional limb
perfusion (IVRLP) exist despite a lack of information regarding safety for synovial
structures in the perfused area. The objective of this study was to determine whether
tiludronate concentrations in synovial structures after IVRLP with low dose (0.5 mg,
LDT) or high dose (50 mg, HDT) tiludronate remain below a value demonstrated
in vitro to be safe for articular cartilage (<19,000 ng/ml), and to determine effects
of tiludronate on synovial fluid cytology variables compared to saline perfused
control limbs. Using a randomized controlled experimental study design, horses
received IVRLP with LDT (n = 6) or HDT (n = 6) in one forelimb and IVRLP with
saline in the contralateral limb. Synovial fluid cytology variables and tiludronate
concentrations were evaluated in navicular bursae (NB), and distal interphalangeal
(DIP) and metacarpophalangeal (MCP) joints one week before and 30–45 min after
IVRLP, and in DIP and MCP joints 24 h after IVRLP. Data were analyzed with 2-way
rmANOVA (p < 0.05). Highest measured synovial fluid tiludronate concentrations
occurred 30–45 min post-perfusion. Mean tiludronate concentrations were
lower in LDT limbs (MCP = 39.6 ± 14.3 ng/ml, DIP = 118.1 ± 66.6 ng/ml, NB
= 82.1 ± 30.2 ng/ml) than in HDT limbs (MCP = 3,745.1 ± 1,536.6 ng/ml,
DIP = 16,274.0 ± 5,460.2 ng/ml, NB = 6,049.3 ± 1,931.7 ng/ml). Tiludronate
concentration was >19,000 ng/ml in DIP joints of two HDT limbs. Tiludronate was
measurable only in synovial fluid from HDT limbs 24 h post-perfusion. There were
no differences in synovial fluid cytology variables between control and treated limbs.
Conclusions. In some horses, IVRLP with HDT may result in synovial fluid
concentrations of tiludronate that may have adverse effects on articular cartilage,
based on in vitro data. IVRLP with LDT is unlikely to promote articular cartilage
degradation. Further studies to determine a safe and effective dose for IVRLP with
tiludronate are needed.
Genre Article
Access Condition http://creativecommons.org/licenses/by/3.0/us/
Topic Veterinary medicine
Identifier Hunter, B. G., Duesterdieck-Zellmer, K. F., & Larson, M. K. (2015). Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses. PeerJ, 3, e889. doi:10.7717/peerj.889

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