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PeerJ2014; 2; e534; doi: 10.7717/peerj.534

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

Abstract: 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.
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Publication Date: 2014-09-04 PubMed ID: 25237596PubMed Central: PMC4157236DOI: 10.7717/peerj.534Google Scholar: Lookup
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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 impact of different doses of intraarticularly administered tiludronate on the cartilage of healthy horses. It found that a high dose led to temporary increases in the synovial total solids and the degradation of proteoglycan in the cartilage with no damage to the cartilage.

Research Method

  • The study was done on eight healthy horses.
  • They were injected once with either a low dose (0.017mg, n = 4) or high dose (50mg, n = 4) of tiludronate into one middle carpal joint. The contralateral joint was injected with saline.
  • Arthrocentesis of the joints was performed before treatment, and again 10 minutes, 24 hours, 48 hours, 7 days, and 14 days after treatment.
  • Researchers measured synovial nucleated cell counts, total solids, tiludronate, sulfated glycosaminoglycan (sGAG), chondroitin sulfate 846 epitope (CS-846, indicates aggrecan synthesis), and collagen type II cleavage neoepitope (C2C) concentrations.
  • Histologic analysis of joint tissues and sGAG quantities in cartilage were also carried out 14 days post-treatment in the high dose tiludronate (HDT) horses.

Findings

  • High dose tiludronate administration led to significantly higher synovial fluid tiludronate concentrations than were safe for cartilage in vitro.
  • Low dose tiludronate horses had lower synovial fluid concentrations that were below levels potentially damaging to cartilage.
  • With HDT, there was a higher concentration of synovial fluid total solids at 24 hours and 7 days, and a higher concentration of sGAG 48 hours post-treatment compared to control joints.
  • Synovial fluid CS-846 concentration increased in control but not treated joints with HDT at 24 and 48 hours post-treatment.
  • All the joints displayed a temporary reduction in synovial fluid C2C concentration compared to pre-treatment levels.
  • HDT-treated and control joints exhibited similar histologic features of articular cartilage and synovial membrane.

Conclusion

  • The research concluded that high dose tiludronate treatment led to a short-term increase in synovial total solids and temporarily escalated the degradation of proteoglycan in the cartilage.
  • Despite this, it did not result in damage to the articular cartilage, meaning its clinical significance might be questionable.
  • The study recommends further investigations into the safety of high dose intraarticular tiludronate in a larger number of horses.

Cite This Article

APA
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

Publication

PeerJ
ISSN: 2167-8359
NlmUniqueID: 101603425
Country: United States
Language: English
Volume: 2
Pages: e534
PII: e534

Researcher Affiliations

Duesterdieck-Zellmer, Katja F
  • Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
Moneta, Lindsey
  • College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
Ott, Jesse F
  • Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
Larson, Maureen K
  • Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
Gorman, Elena M
  • Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
Hunter, Barbara
  • Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
Löhr, Christiane V
  • Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
Payton, Mark E
  • Department of Statistics, Oklahoma State University , Stillwater, OK , USA.
Morré, Jeffrey T
  • Department of Chemistry, Oregon State University , Corvallis, OR , USA.
Maier, Claudia S
  • Department of Chemistry, Oregon State University , Corvallis, OR , USA.

Grant Funding

  • P30 ES000210 / NIEHS NIH HHS

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Citations

This article has been cited 1 times.
  1. Hunter BG, Duesterdieck-Zellmer KF, Larson MK. Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses. PeerJ 2015;3:e889.
    doi: 10.7717/peerj.889pubmed: 25945303google scholar: lookup
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