Clodronate detection and effects on markers of bone resorption are prolonged following a single administration to horses.
analgesic
bisphosphonate
bone
clodronate
horse
pharmacokinetics
Journal
Equine veterinary journal
ISSN: 2042-3306
Titre abrégé: Equine Vet J
Pays: United States
ID NLM: 0173320
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
20
12
2021
accepted:
10
07
2022
medline:
9
6
2023
pubmed:
25
7
2022
entrez:
24
7
2022
Statut:
ppublish
Résumé
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. (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. Randomised controlled experimental study. 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. 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. Relatively small number of horses studied. 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. 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. (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. Estudo controlado randomizado. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
OBJECTIVES
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.
STUDY DESIGN
METHODS
Randomised controlled experimental study.
METHODS
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
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.
MAIN LIMITATIONS
CONCLUSIONS
Relatively small number of horses studied.
CONCLUSIONS
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.
CONTEXTO
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.
OBJETIVOS
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.
DELINEAMENTO DO ESTUDO
UNASSIGNED
Estudo controlado randomizado.
METODOLOGIA
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.
RESULTADOS
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.
Autres résumés
Type: Publisher
(por)
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.
Substances chimiques
Clodronic Acid
0813BZ6866
Diphosphonates
0
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
696-706Subventions
Organisme : Grayson-Jockey Club Research Foundation
Organisme : The Viola Foundation
Informations de copyright
© 2022 EVJ Ltd.
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