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Journal of animal science2025; 103; doi: 10.1093/jas/skaf132

Effects of clodronate disodium on endocrine regulators of calcium in yearling horses.

Abstract: Extra-label bisphosphonate (BP) use in juvenile horses is anecdotally reported, primarily for analgesic effects, despite the limited scientific understanding of biologic impacts on skeletally immature horses undergoing exercise. The objective of this study was to determine the effects of clodronate disodium (CD), a form of BP, on endocrine regulators of calcium. Thus, 32 yearling Quarter Horses were stratified by age (500 ± 13 d), body weight (BW; 336 ± 26 kg), sex (n = 16 geldings, n = 16 fillies), and initial bone optical density into 1 of 4 treatment groups for a 168-d trial. The experimental period was divided into 2 exercise phases to model industry standards. Investigators were blinded to treatment, and all horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW CD (OSPHOS) or saline (placebo) on days 0, 42, 84, and 126. Treatments consisted of control (CON; n = 8), 1-dose (1X; n = 8; day 84), 2-dose (2X; n = 8; day 0, 84), and 4-dose groups (4X; n = 8; days 0, 42, 84, 126). Serum samples were collected, and physical measurements were recorded including BW, wither height, hip height, body length, and heart girth circumference (HG) every 42 d, prior to treatment administration. Serum samples were analyzed for growth hormone (GH), calcitonin, parathyroid hormone (PTH), and ionized calcium (Ca2+). Data were analyzed using MIXED and CORR procedures of SAS. All physical measurements increased over time (P ≤ 0.01) but were not affected by treatment (P ≥ 0.62). Similarly, there was no effect of treatment for GH (P = 0.44), but concentrations tended to decrease over time (P = 0.09). A treatment × day interaction was observed for PTH (P = 0.05) where concentrations increased following a second CD dose. Specifically, concentrations increased on day 84 in 4X and on day 126 in 2X following the second treatment with CD whereas 1X and CON remained unchanged. Despite the increase in PTH, there was no effect on calcitonin (P ≥ 0.33). Ionized calcium concentrations decreased over time (P < 0.01) with no effect of treatment (P = 0.26). Parathyroid hormone was negatively correlated with serum Ca2+ (r = -0.28, P < 0.01), whereas calcitonin was not correlated with serum Ca2+ (r = 0.06, P = 0.48) nor PTH (r = -0.13, P = 0.12). According to these results, CD has no effect on growth morphometrics, but its use transiently increases PTH concentrations after 2 doses. Despite limited scientific understanding of the impacts on juvenile horses, extra-label use of bisphosphonates is anecdotally reported to be widespread. This study was conducted to determine the effects of clodronate disodium (CD), a specific bisphosphonate, on hormones associated with blood calcium regulation. Thirty-two yearling Quarter Horses were given either saline, 1-dose, 2-doses, or 4-doses of CD over the course of 168 d. Growth measurements (height, weight, and body measurements) and serum samples were collected throughout. Blood samples were analyzed for blood calcium and hormones associated with blood calcium. All physical measurements increased over time but were not affected by CD. Parathyroid hormone temporarily increased following a second dose in horses that received multiple doses. Ionized calcium concentrations decreased over time and growth hormone concentrations tended to decrease over time. The present study provides the framework for future research on the relationship between CD administration in juvenile horses and the endocrine regulation of calcium.
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Publication Date: 2025-04-22 PubMed ID: 40259552PubMed Central: PMC12124253DOI: 10.1093/jas/skaf132Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

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 article investigates the effects of a bisphosphonate known as clodronate disodium (CD) on endocrine regulators of calcium in yearling horses. It concludes that CD has no impact on the horses’ growth but results in a temporary increase of parathyroid hormone (PTH) concentrations after two doses.

Research Context

  • The use of bisphosphonates (BP), particularly clodronate disodium (CD), in juvenile horses is a common practice despite limited scientific data about its impacts on horses’ development, primarily concerning their skeletal health when combined with exercise.
  • The study focuses on understanding the effects of BP use, focusing on clodronate disodium (CD), on endocrine regulators of calcium in yearling horses, an important aspect given the major role of calcium in bone development and health.

Study Design and Procedure

  • The experiment involved 32 yearling Quarter Horses who were segregated into one of four treatment groups. The groups consisted of control, single-dose, two-dose, and four-dose, with each group having eight horses.
  • All horses received iso-volumetric intramuscular injections of either CD or saline (placebo) on certain set days. Physical measurements like body weight, wither and hip height, body length, and heart girth circumference were recorded every 42 days.
  • Serum samples were collected for analysis of growth hormone, calcitonin, parathyroid hormone (PTH), and ionized calcium (Ca2+), key endocrine regulators of calcium.

Results and Conclusion

  • Physical measurements depicted increase over time but were not impacted by the CD treatment. Additionally, growth hormone (GH) levels showed no effect of CD but tended towards a decrease over time.
  • There was a significant increase of parathyroid hormone (PTH) concentration after the administration of a second CD dosage. Despite this increase, there was no effect on calcitonin levels.
  • The concentration of ionized calcium decreased over the period but showed no impact of CD treatment. PTH was found to have a negative correlation with serum Ca2+, while calcitonin showed no correlation with either serum Ca2+ or PTH.
  • The study concluded that while CD does not impact growth metrics, it does result in a transient increase in PTH concentrations after two doses. The long-term effects of such increases and their impact on the horse’s bone health and overall well-being remain a potential area of further research.

Cite This Article

APA
Conrad MB, Leatherwood JL, Paris BL, George JM, Martinez RE, Vergara-Hernandez FB, Nielsen BD, Colbath AC, Arnold CE, Glass KG, Welsh TH, Bradbery AN. (2025). Effects of clodronate disodium on endocrine regulators of calcium in yearling horses. J Anim Sci, 103. https://doi.org/10.1093/jas/skaf132

Publication

Journal of animal science
ISSN: 1525-3163
NlmUniqueID: 8003002
Country: United States
Language: English
Volume: 103

Researcher Affiliations

Conrad, Matthew B
  • Department of Animal and Range Sciences, Montana State University, Bozeman, MT 59717, USA.
Leatherwood, Jessica L
  • Department of Animal Science, Tarleton State University, Stephenville, TX 76402, USA.
  • Department of Animal Science, Texas A&M AgriLife Research and Texas A&M University, College Station, TX 77843, USA.
Paris, Brittany L
  • Department of Animal Science, Texas A&M AgriLife Research and Texas A&M University, College Station, TX 77843, USA.
George, James M
  • Department of Animal Science, Tarleton State University, Stephenville, TX 76402, USA.
Martinez, Rafael E
  • Department of Animal Science, Tarleton State University, Stephenville, TX 76402, USA.
  • Department of Animal Science, Texas A&M AgriLife Research and Texas A&M University, College Station, TX 77843, USA.
Vergara-Hernandez, Fernando B
  • Escuela de Medicina Veterinaria, Facultad de Recursos Naturales y Medicina Veterinaria, Universidad Santo Tomás, Viña del Mar, Chile.
Nielsen, Brian D
  • Department of Animal Science, Michigan State University, East Lansing, MI 48824, USA.
Colbath, Aimee C
  • Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA.
Arnold, Carolyn E
  • School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA.
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX 77843, USA.
Glass, Kati G
  • Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX 77843, USA.
Welsh, Thomas H
  • Department of Animal Science, Texas A&M AgriLife Research and Texas A&M University, College Station, TX 77843, USA.
Bradbery, Amanda N
  • Department of Animal and Range Sciences, Montana State University, Bozeman, MT 59717, USA.

MeSH Terms

  • Animals
  • Horses / blood
  • Horses / physiology
  • Male
  • Female
  • Calcium / blood
  • Calcium / metabolism
  • Clodronic Acid / pharmacology
  • Clodronic Acid / administration & dosage
  • Bone Density Conservation Agents / pharmacology
  • Bone Density Conservation Agents / administration & dosage
  • Calcitonin / blood
  • Parathyroid Hormone / blood

References

This article includes 45 references
  1. Al Elq AH. Symptomatic hypocalcemia associated with zoledronic acid treatment for osteoporosis: a case report. Oman Med J 28:e043.
    doi: 10.5001/omj.2013.42pmc: PMC6667807pubmed: 31435469google scholar: lookup
  2. Andreasson U, Perret-Liaudet A, van Waalwijk van Doorn LJC, Blennow K, Chiasserini D, Engelborghs S, Fladby T, Genc S, Kruse N, Kuiperij HB. A practical guide to immunoassay method validation. Front Neurol 6:179.
    doi: 10.3389/fneur.2015.00179pmc: PMC4541289pubmed: 26347708google scholar: lookup
  3. Antoniazzi F, Monti E, Venturi G, Franceschi R, Doro F, Gatti D, Zamboni G, Tató L. GH in combination with bisphosphonate treatment in osteogenesis imperfecta. Eur J Endocrinol 163:479–487.
    doi: 10.1530/EJE-10-0208pubmed: 20592128google scholar: lookup
  4. Bagger LW, Hansen PKD, Schwarz P, Nielsen BR. Severe hypophosphataemia following oral bisphosphonate treatment in a patient with osteoporosis. BMJ Case Rep 13:e235083.
    doi: 10.1136/bcr-2020-235083pmc: PMC7545506pubmed: 33033001google scholar: lookup
  5. Basu G, Mohapatra A. Interactions between thyroid disorders and kidney disease. Indian J Endocrinol Metab 16:204–213.
    doi: 10.4103/2230-8210.93737pmc: PMC3313737pubmed: 22470856google scholar: lookup
  6. Biermasz NR, Hamdy NAT, Janssen YJH, Roelfsema F. Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: a randomized controlled trial. J Clin Endocrinol Metab 86:3079–3085.
    doi: 10.1210/jcem.86.7.7669pubmed: 11443170google scholar: lookup
  7. Braithwaite GD. The effect of growth hormone on calcium metabolism in the sheep. Br J Nutr 33:309–314.
    doi: 10.1079/bjn19750036pubmed: 1125163google scholar: lookup
  8. Bronner F. Extracellular and intracellular regulation of calcium homeostasis. ScientificWorldJ 1:919–925.
    doi: 10.1100/tsw.2001.489pmc: PMC6084056pubmed: 12805727google scholar: lookup
  9. Brumsen C, Hamdy NAT, Papapoulos SE. Long-term effects of bisphosphonates on the growing skeleton: studies of young patients with severe osteoporosis. Medicine (Baltim) 76:266–283.
    doi: 10.1097/00005792-199707000-00005pubmed: 9279333google scholar: lookup
  10. Cunningham K, Fowler SH. A study of growth and development in the quarter horse. LSU Agricultural Experiment Station Reports 546.
  11. De Graaf-Roelfsema E de, Veldhuis PP, Keizer HA, van Ginneken MME, van Dam KG, Johnson ML, Barneveld A, Menheere PPCA, van Breda E, Wijnberg ID. Overtrained horses alter their resting pulsatile growth hormone secretion. Am J Physiol Regul Integr Comp Physiol 297:R403–R411.
    doi: 10.1152/ajpregu.90778.2008pmc: PMC4062293pubmed: 19494168google scholar: lookup
  12. Denoix JM, Thibaud D, Riccio B. Tiludronate as a new therapeutic agent in the treatment of navicular disease: a double-blind placebo-controlled clinical trial. Equine Vet J 35:407–413.
    doi: 10.2746/042516403776014226pubmed: 12880010google scholar: lookup
  13. Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 83:1032–1045.
    doi: 10.4065/83.9.1032pmc: PMC2667901pubmed: 18775204google scholar: lookup
  14. Edwards L, Magdesian KG. Retrospective evaluation of acute kidney injury in horses treated with nonnitrogenous bisphosphonates (2013–2020): 8 cases. J Vet Emerg Crit Care 33:685–695.
    doi: 10.1111/vec.13324pubmed: 37695208google scholar: lookup
  15. Food and Drug Administration. Freedom of information summary. NADA 141-427, OSPHOS, Original New Animal Drug. Approval, April 28, 2014. .
  16. Gaffney-Stomberg E, MacArthur MR, McClung JP. Parathyroid hormone (PTH) and the relationship between PTH and bone health: structure, physiology, actions, and ethnicity. p. 443–461.
  17. Garcia JM, Merriam GR, Kargi AY, Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariva K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrere B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP. Growth hormone in aging. Endotext South Dartmouth: MDText.com.
  18. Gilday R, Richard H, Beauchamp G, Fogarty U, Laverty S. Abundant osteoclasts in the subchondral bone of the juvenile thoroughbred metacarpus suggest an important role in joint maturation. Equine Vet J 52:733–742.
    doi: 10.1111/evj.13235pubmed: 31972056google scholar: lookup
  19. Giustina A, Mazziotti G, Canalis E. Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559.
    doi: 10.1210/er.2007-0036pmc: PMC2726838pubmed: 18436706google scholar: lookup
  20. Harli WP, Kasyim H, Tandean P, Bakri S, Tabri NA, Seweng A. Correlation between serum calcium and parathyroid hormone in chronic kidney disease patients. Bali Med J 13:662–667.
    doi: 10.15562/bmj.v13i1.5106google scholar: lookup
  21. Khan AA, Gurnani PK, Peksa GD, Whittier WL, DeMott JM. Bisphosphonate versus bisphosphonate and calcitonin for the treatment of moderate to severe hypercalcemia of malignancy. Ann Pharmacother 55:277–285.
    doi: 10.1177/1060028020957048pubmed: 32885992google scholar: lookup
  22. Knight MJ, Hyatt PJ. The effect of bisphosphonates on calcium and parathyroid hormone levels in patients with primary hyperparathyroidism over 2 years. Endocrine Abstracts 12:P2.
  23. Koh NYY, Miszkiewicz JJ, Fac ML, Wee NKY, Sims NA. Preclinical rodent models for human bone disease, including a focus on cortical bone. Endocrine Reviews 45:493–520.
    doi: 10.1210/endrev/bnae004pmc: PMC11244217pubmed: 38315213google scholar: lookup
  24. Liamis G, Milionis HJ, Elisaf M. Medication-induced hypophosphatemia: a review. QJM 103:449–459.
    doi: 10.1093/qjmed/hcq039pubmed: 20356849google scholar: lookup
  25. Miller PD, Jamal SA, Evenepoel P, Eastell R, Boonen S. Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res 28:2049–2059.
    doi: 10.1002/jbmr.2058pubmed: 23907861google scholar: lookup
  26. Mitchell A, Watts AE, Ebetino FH, Suva LJ. Bisphosphonate use in the horse: what is good and what is not?. BMC Vet Res 15:211.
    doi: 10.1186/s12917-019-1966-xpmc: PMC6591999pubmed: 31234844google scholar: lookup
  27. NRC. Nutrient requirements of horses. Washington (DC): National Academies Press.
  28. Recker RR, Lewiecki EM, Miller PD, Reiffel J. Safety of bisphosphonates in the treatment of osteoporosis. Am J Med 122:S22–S32.
    doi: 10.1016/j.amjmed.2008.12.004pubmed: 19187809google scholar: lookup
  29. Rodan GA. Bone homeostasis. Proc Natl Acad Sci U S A 95:13361–13362.
    doi: 10.1073/pnas.95.23.13361pmc: PMC33917pubmed: 9811806google scholar: lookup
  30. Rodan GA, Fleisch HA. Bisphosphonates: mechanisms of action. J Clin Invest 97:2692–2696.
    doi: 10.1172/JCI118722pmc: PMC507360pubmed: 8675678google scholar: lookup
  31. Rogers CW, Gee EK, Dittmer KE. Growth and bone development in the horse: when is a horse skeletally mature?. Animals (Basel) 11:3402.
    doi: 10.3390/ani11123402pmc: PMC8698045pubmed: 34944179google scholar: lookup
  32. Rourke KM, Kohn CW, Levine AL, Rosol TJ, Toribio RE. Rapid calcitonin response to experimental hypercalcemia in healthy horses. Domest Anim Endocrinol 36:197–201.
    doi: 10.1016/j.domaniend.2008.11.004pubmed: 19135828google scholar: lookup
  33. Rudman D, Kutner MH, Rogers CM, Lubin MF, Fleming GA, Bain RP. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest 67:1361–1369.
    doi: 10.1172/jci110164pmc: PMC370702pubmed: 7194884google scholar: lookup
  34. Sahni M, Guenther HL, Fleisch H, Collin P, Martin TJ. Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. J Clin Invest 91:2004–2011.
    doi: 10.1172/JCI116422pmc: PMC288198pubmed: 8486770google scholar: lookup
  35. Shamonki IM, Frumar AM, Tataryn IV, Meldrum DR, Davidson BH, Parthemore JG, Judd HL, Defto LJ. Age-related changes of calcitonin secretion in females. J Clin Endocrinol Metab 50:437–439.
    doi: 10.1210/jcem-50-3-437pubmed: 7358830google scholar: lookup
  36. Song YK, Kim JM, Park SJ, Lee S-K. Increase in the serum parathyroid hormone level during a bisphosphonate drug holiday. J Bone Metab 21:217–222.
    doi: 10.11005/jbm.2014.21.3.217pmc: PMC4170085pubmed: 25247160google scholar: lookup
  37. Sonntag J, Vogel M, Geserick M, Eckelt F, Korner A, Raue F, Kiess W, Kratzsch J. Age-related association of calcitonin with parameters of anthropometry, bone and calcium metabolism during childhood. Horm Res Paediatr 93:361–370.
    doi: 10.1159/000512107pubmed: 33311025google scholar: lookup
  38. Srinivasan A, Wong FK, Karponis D. Calcitonin: a useful old friend. J Musculoskelet Neuronal Interact 20:600–609.
    pmc: PMC7716677pubmed: 33265089
  39. Suva LJ, Cooper A, Watts AE, Ebetino FH, Price J, Gaddy D. Bisphosphonates in veterinary medicine: the new horizon for use. Bone 142:115711.
    doi: 10.1016/j.bone.2020.115711pubmed: 33141069google scholar: lookup
  40. Toribio RE. Disorders of calcium and phosphate metabolism in horses. Vet Clin North Am Equine Pract 27:129–147.
    doi: 10.1016/j.cveq.2010.12.010pubmed: 21392658google scholar: lookup
  41. Toussaint ND, Elder GJ, Kerr PG. Bisphosphonates in chronic kidney disease; balancing potential benefits and adverse effects on bone and soft tissue. Clin J Am Soc Nephrol 4:221–233.
    doi: 10.2215/CJN.02550508pubmed: 18987295google scholar: lookup
  42. Van Abel M, Hoenderop JGJ, Van Der Kemp AWC M, Friedlaender MM, Van Leeuwen JPTM, Bindels RJM. Coordinated control of renal Ca2+ transport proteins by parathyroid hormone. Kidney Int 68:1708–1721.
    doi: 10.1111/J.1523-1755.2005.00587.Xpubmed: 16164647google scholar: lookup
  43. Vasikaran SD. Bisphosphonates: an overview with special reference to alendronate. Ann Clin Biochem 38:608–623.
    doi: 10.1258/0004563011901037pubmed: 11732644google scholar: lookup
  44. Whitfield CT, Schoonover MJ, Holbrook TC, Payton ME, Sippel KM. Quantitative assessment of two methods of tiludronate administration for the treatment of lameness caused by navicular syndrome in horses. Am J Vet Res 77:167–173.
    doi: 10.2460/ajvr.77.2.167pubmed: 27027711google scholar: lookup
  45. Zhu ED, Louis L, Brooks DJ, Bouxsein ML, Demay MB. Effect of Bisphosphonates on the Rapidly Growing Male Murine Skeleton. Endocrinology 155:1188–1196.
    doi: 10.1210/en.2013-1993pmc: PMC3959604pubmed: 24422540google scholar: lookup

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