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Home / Equine Research Bank / Equine Vet J / Clodronate detection and effects on markers of bone resorpti...
Equine veterinary journal2022; 55(4); 696-706; doi: 10.1111/evj.13866

Clodronate detection and effects on markers of bone resorption are prolonged following a single administration to horses.

Abstract: Clodronate is a potent antiresorptive agent labelled for use in horses over 4 years of age, for the treatment of navicular syndrome. Concerns regarding the extra-label use of clodronate in equine athletes, such as racehorses, have been raised as inhibition of osteoclast activity by clodronate has been postulated to interfere with normal bone healing, which is imperative to the repair of microfractures. The paucity of data describing the long-term pharmacokinetics of clodronate and effects on biomarkers of bone resorption necessitates further study. Objective: (1) To determine clodronate concentrations in blood and urine over a 6-month period in horses undergoing treadmill exercise and (2) to assess the effects of clodronate on protein biomarkers of bone remodelling in this same group of horses. Methods: Randomised controlled experimental study. Methods: Seven exercised Thoroughbred horses received a single im administration of 1.8 mg/kg clodronate and four horses received an equivalent volume of saline. Blood and urine samples were collected prior to, during and for 182 days post drug administration for drug concentration determination using liquid chromatography-tandem mass spectrometry, and determination of protein biomarker (CTX-1 and TRAcP5B) concentrations. Results: Clodronate was detectable in blood for 14-175 days and for up to 175 days in urine. For some horses, concentrations were nondetectable at one time point but detectable at a subsequent time point. The terminal serum half-life ranged from 1.80 to 283.9 days. CTX-1 concentrations were significantly higher, relative to baseline, in both treated and control groups while concentrations of TRAcP5B were significantly lower in the treated group. Conclusions: Relatively small number of horses studied. Conclusions: Based on assessment of protein biomarkers, clodronate appears to influence osteoclasts at label doses. Furthermore, results of this study support racing regulations that preclude horses administered bisphosphonates for medical reasons, from racing for a prolonged period of time. Unassigned: Clodronato é um agente antirreabsortivo potente e recomendado para o uso em cavalos com mais de 4 anos de idade, para o tratamento da síndrome do navicular. Há preocupação com o uso indiscriminado de clodronato em equinos atletas, como cavalos de corrida, já que a inibição da atividade dos osteoclastos pelo clodronato tem sido postulada em interferir na cicatrização óssea normal, o que é essencial para a cicatrização de microfraturas. A escassez de informação quanto às ações prolongadas do uso de clodronato e seus efeitos nos biomarcadores de reabsorção óssea requere mais estudos. Objective: (1) Determinar a concentração de clodronato no sangue e urina por um período de 6 meses em cavalos submetidos ao exercício em esteira e (2) acessar os efeitos de clodronato nos biomarcadores de remodelação óssea no mesmo grupo de cavalos. Unassigned: Estudo controlado randomizado. Methods: Sete cavalos Puro-Sangue Inglês em exercício receberam uma única dose im de 1.8 mg/kg de clodronato e 4 cavalos receberam um volume equivalente de solução fisiológica. Amostras de sangue e urina foram coletadas antes, durante e por 182 dias após a administração de clodronato. Valores de concentração da droga foram determinados utilizando cromatografia líquida-espectrometria de massa (LC-MS/MS), e determinação da concentração de biomarcadores (CTX-1 e TRAcP5B) também foi realizada. Results: Clodronato foi detectado no sangue por 14-175 dias e por até 175 dias na urina. Para alguns equinos, a concentração foi não-detectável em um momento, mas detectável no próximo momento. O valor terminal da vida-média em soro foi 1.80-283.9 dias. A concentração de CTX-1 foi significativamente elevada, relativo às amostras iniciais, em ambos os grupos (tratamento e controle), enquanto as concentrações de TRAcP5B foram significativamente menores no grupo de cavalos tratados. PRINCIPAIS LIMITAÇÕES: Número relativamente pequenos de cavalos no estudo. CONCLUSÕES: Baseado nos resultados dos biomarcadores, clodronato parece influencia osteoclastos na dose recomendada. Além disso, os resultados deste estudo suportam o regulamento de cavalos de corrida que impedem que cavalos que receberam bifosfonatos por razão médica de competir por um período de tempo prolongado.
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Publication Date: 2022-08-23 PubMed ID: 35871470DOI: 10.1111/evj.13866Google 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 examines the long-term impacts of giving clodronate, an anti-bone resorption drug often used to treat navicular syndrome, to Thoroughbred horses. It aims to understand this drug’s biomechanical effects and its presence in blood and urine samples over a 6-month period.

Research Methodology

  • The experiment involved a randomized control study of eleven Thoroughbred horses.
  • Seven of the horses received a single intramuscular administration of 1.8 mg/kg of clodronate, while the other four horses were given an equivalent volume of saline, serving as the control group.
  • Researchers then collected blood and urine samples over a period of 182 days post-drug administration.
  • These samples were analyzed to determine the concentration of clodronate using liquid chromatography-tandem mass spectrometry.
  • They also checked for concentrations of protein biomarkers CTX-1 and TRAcP5B, which are indicators of bone remodelling.

Results

  • The results showed that clodronate was detectable in the horse’s blood for 14-175 days and up to 175 days in urine samples.
  • In some horses, clodronate was nondetectable at one time point but was found at a subsequent time point.
  • The terminal serum half-life ranged from 1.80 to 283.9 days.
  • Concentrations of CTX-1 were significantly higher relative to baseline in both the treated and control groups. However, TRAcP5B concentrations were significantly lower in the treated group.

Conclusions

  • The study suggested that clodronate has a long-lasting influence on osteoclasts, even at the prescribed label doses.
  • The study concluded that this justifies regulations barring horses from racing for a prolonged period after being administered bisphosphonates for medical reasons.
  • Although the results are intriguing, one limitation identified was the relatively small number of horses included in the study.

Cite This Article

APA
Knych HK, Finno CJ, Katzman S, Ryan D, McKemie DS, Kass PH, Arthur RM. (2022). Clodronate detection and effects on markers of bone resorption are prolonged following a single administration to horses. Equine Vet J, 55(4), 696-706. https://doi.org/10.1111/evj.13866

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 55
Issue: 4
Pages: 696-706

Researcher Affiliations

Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
  • Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.
Finno, Carrie J
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA.
Katzman, Scott
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, USA.
Ryan, Declan
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
McKemie, Daniel S
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
Kass, Philip H
  • Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.
Arthur, Rick M
  • School of Veterinary Medicine, University of California, Davis, California, USA.

MeSH Terms

  • Horses
  • Animals
  • Clodronic Acid / pharmacology
  • Clodronic Acid / therapeutic use
  • Bone Resorption / drug therapy
  • Bone Resorption / veterinary
  • Diphosphonates / therapeutic use
  • Body Fluids
  • Biomarkers
  • Horse Diseases / drug therapy

Grant Funding

  • Grayson-Jockey Club Research Foundation
  • The Viola Foundation

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Citations

This article has been cited 3 times.
  1. Reis IL, Lopes B, Sousa P, Sousa AC, Caseiro AR, Mendonça CM, Santos JM, Atayde LM, Alvites RD, Maurício AC. Equine Musculoskeletal Pathologies: Clinical Approaches and Therapeutical Perspectives-A Review. Vet Sci 2024 Apr 26;11(5).
    doi: 10.3390/vetsci11050190pubmed: 38787162google scholar: lookup
  2. Vasileva R, Chaprazov T, Milanova A. Effects of Erythropoietin-Promoted Fracture Healing on Bone Turnover Markers in Cats. J Funct Biomater 2024 Apr 17;15(4).
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  3. Wilcox CV, Knych HK, Katzman SA, Arthur RM, Rodriguez V, Finno CJ. Effect of clodronate on gene expression in the peripheral blood of horses. J Vet Pharmacol Ther 2024 May;47(3):187-192.
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