Detection and residence time of bisphosphonates in bone of horses.
Abstract: Bisphosphonates are potent anti-resorptive agents that have the potential to adversely affect bone healing in equine athletes, and normal bone adaption in young racehorses. A concern exists that bisphosphonate inhibition of normal bone metabolism could lead to increased bone fractures during high-intensity exercise. We found only a single report describing concentrations of tiludronate in the bone of horses, and no studies describing clodronate. Knowledge of the residence time in bone could allow for a better understanding of the long-term effects of these compounds. Our objectives were to develop a method for detection of bisphosphonates in bone and add to the limited information available regarding the disposition of these drugs in the bone of horses. Two horses received clodronate and 2 tiludronate disodium. Postmortem collection of bones and teeth occurred either 4 or 30 d post drug administration. Additionally, postmortem blood, synovial fluid, aqueous humor, and bone samples from racehorses with various histories of bisphosphonate administration were collected, and concentrations determined using the developed LC-MS/MS method. Bisphosphonates were detected in bones and teeth tested at 4 and 30 d. In a postmortem sample, clodronate was detected in bone from a horse with reported administration 18 mo prior; clodronate was not detected in other sample types collected from this horse. Bisphosphonates reside in bone for extended periods of time, which could lead to potential long-term effects, increasing the potential for bone fractures in young and/or athletic horses.
Publication Date: 2021-12-18 PubMed ID: 34918585PubMed Central: PMC8689024DOI: 10.1177/10406387211050049Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
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.
This study explores the long-term presence and impact of bisphosphonates, a type of anti-resorptive agent, in the bones of horses, and particularly athletic racehorses. The researchers developed a method to detect these compounds in horse bones, collected from both living and deceased horses, and found that bisphosphonates remain in the bones for notable lengths of time, potentially increasing the risk of bone fractures.
Research Objectives and Approach
- The primary objectives of this research were to devise a detection system for bisphosphonates in the bones of horses and to expand current knowledge regarding these drugs’ disposition within horse bones.
- The research team administered bisphosphonates (specifically clodronate and tiludronate disodium) to two horses each, and then collected bone and teeth samples postmortem at either 4 or 30 days after the drugs were administered.
- In addition to this, blood, bone, synovial fluid, and aqueous humor samples were collected from racehorses with diverse histories of bisphosphonate administration.
Findings of the Study
- The developed detection method succeeded in identifying bisphosphonates in the tested bone and teeth samples at both 4 and 30 days after administration.
- Notably, in a postmortem sample, clodronate was detected in bone from a horse 18 months after the drug had been administered. However, clodronate was not detected in other sample types collected from this particular horse.
- These findings reaffirmed the study’s hypothesis that bisphosphonates reside in horse bone for extended periods, which raises concerns over potential long-term effects, including an increased probability of bone fractures in young or athletic horses.
Implications of the Research
- This study could pave the way for further investigations into the long-term effects of bisphosphonate use in horses, especially regarding potential interference with normal bone metabolism and the subsequent risk of bone fractures during intense exercise.
- The newly developed detection method for bisphosphonates in bone can also be applied in future research for its efficient and accurate results.
Cite This Article
APA
Knych HK, Janes J, Kennedy L, McKemie DS, Arthur RM, Samol MA, Uzal FA, Scollay M.
(2021).
Detection and residence time of bisphosphonates in bone of horses.
J Vet Diagn Invest, 34(1), 23-27.
https://doi.org/10.1177/10406387211050049 Publication
Researcher Affiliations
- K.L. Maddy Equine Analytical Pharmacology Laboratory, University of California, Davis, CA, USA.
- University of Kentucky Veterinary Diagnostic Laboratory, Lexington, KY, USA.
- University of Kentucky Veterinary Diagnostic Laboratory, Lexington, KY, USA.
- K.L. Maddy Equine Analytical Pharmacology Laboratory, University of California, Davis, CA, USA.
- School of Veterinary Medicine, University of California, Davis, CA, USA.
- California Animal Health and Food Safety Laboratory, San Bernardino Laboratory, University of California, Davis, CA, USA.
- California Animal Health and Food Safety Laboratory, San Bernardino Laboratory, University of California, Davis, CA, USA.
- Kentucky Horse Racing Commission, Lexington, KY, USA.
MeSH Terms
- Animals
- Chromatography, Liquid / veterinary
- Diphosphonates
- Horses
- Tandem Mass Spectrometry / veterinary
Conflict of Interest Statement
Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
References
This article includes 16 references
- Black DM. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996;348:1535–1541.
- Cheng A. The dental implications of bisphosphonates and bone disease. Aust Dent J 2005;50(4 Suppl 2):S4–S13.
- Crépin S. Osteonecrosis of the jaw induced by clodronate, an alkylbiphosphonate: case report and literature review. Eur J Clin Pharmacol 2010;66:547–554.
- Delguste C. Assessment of a bone biopsy technique for measuring tiludronate in horses: a preliminary study. Can J Vet Res 2011;75:128–133.
- Huja SS. Remodeling dynamics in the alveolar process in skeletally mature dogs. Anat Rec A Discov Mol Cell Evol Biol 2006;288:1243–1249.
- Krueger CR. Pharmacokinetics and pharmacodynamics of clodronate disodium evaluated in plasma, synovial fluid and urine. Equine Vet J 2020;52:725–732.
- Lai P. A postmenopausal osteoporotic woman losing bone mineral density despite bisphosphonates. Malays Fam Physician 2013;8:47–52.
- Lee SH. Position statement: drug holiday in osteoporosis treatment with bisphosphonates in South Korea. J Bone Metab 2015;22:167–174.
- Li Z. Osteoclast and its roles in calcium metabolism and bone development and remodeling. Biochem Biophys Res Commun 2006;343:345–350.
- nOsphos (clodronate injection) [Package insert]. Dechra, 2018. https://www.dechra-us.com/Admin/Public/Download.aspx?file=Files%2FFiles%2FProductDownloads%2Fus%2Fosphos-pack-insert.pdf
- Popot MA. HPLC/ESI-MSn method for non-amino bisphosphonates: application to the detection of tiludronate in equine plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2014;958:108–116.
- Rosenqvist K. Evaluating optimal combination of clodronate and bioactive glass for dental application. Int J Pharm 2014;468:112–120.
- Shima Y. Use of bisphosphonates for the treatment of stress fractures in athletes. Knee Surg Sports Traumatol Arthrosc 2009;17:542–550.
- Storm T. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990;322:1265–1271.
- Suva LJ. Bisphosphonates in veterinary medicine: the new horizon for use. Bone 2021;142:115711.
- Uchida K. Effects of alendronate on bone metabolism in glucocorticoid-induced osteoporosis measured by 18F-fluoride PET: a prospective study. J Nucl Med 2009;50:1808–1814.
Citations
This article has been cited 2 times.- 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.
- Vergara-Hernandez FB, Nielsen BD, Colbath AC. Is the Use of Bisphosphonates Putting Horses at Risk? An Osteoclast Perspective. Animals (Basel) 2022 Jul 3;12(13).
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
