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BMC veterinary research2019; 15(1); 211; doi: 10.1186/s12917-019-1966-x

Bisphosphonate use in the horse: what is good and what is not?

Abstract: Bisphosphonates (BPs) are a family of molecules characterized by two key properties: their ability to bind strongly to bone mineral and their inhibitory effects on mature osteoclasts and thus bone resorption. Chemically two groups of BPs are recognized, non-nitrogen-containing and nitrogen-containing BPs. Non-nitrogen-containing BPs incorporate into the energy pathways of the osteoclast, resulting in disrupted cellular energy metabolism leading to cytotoxic effects and osteoclast apoptosis. Nitrogen-containing BPs primarily inhibit cholesterol biosynthesis resulting in the disruption of intracellular signaling, and other cellular processes in the osteoclast. BODY: BPs also exert a wide range of physiologic activities beyond merely the inhibition of bone resorption. Indeed, the breadth of reported activities include inhibition of cancer cell metastases, proliferation and apoptosis in vitro. In addition, the inhibition of angiogenesis, matrix metalloproteinase activity, altered cytokine and growth factor expression, and reductions in pain have been reported. In humans, clinical BP use has transformed the treatment of both post-menopausal osteoporosis and metastatic breast and prostate cancer. However, BP use has also resulted in significant adverse events including acute-phase reactions, esophagitis, gastritis, and an association with very infrequent atypical femoral fractures (AFF) and osteonecrosis of the jaw (ONJ). Conclusions: Despite the well-characterized health benefits of BP use in humans, little is known regarding the effects of BPs in the horse. In the equine setting, only non-nitrogen-containing BPs are FDA-approved primarily for the treatment of navicular syndrome. The focus here is to discuss the current understanding of the strengths and weaknesses of BPs in equine veterinary medicine and highlight the future utility of these potentially highly beneficial drugs.
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Publication Date: 2019-06-24 PubMed ID: 31234844PubMed Central: PMC6591999DOI: 10.1186/s12917-019-1966-xGoogle 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 article explores the benefits and risks of using bisphosphonates (BPs), compounds used to treat bone disorders, in equines (horses), with a particular focus on non-nitrogen-containing BPs, the only type approved by the FDA for treating navicular syndrome in horses.

Properties of Bisphosphonates

  • Bisphosphonates are characterized by their strong bond to bone mineral and inhibitory effects on mature osteoclasts, a type that breaks down bone, thereby reducing bone resorption (loss).
  • There are two chemical groups of bisphosphonates: non-nitrogen-containing and nitrogen-containing, each with a different mechanism of action within the osteoclast cells that impacts the cell’s energy processes and cholesterol biosynthesis respectively.

Physiological Activities

  • Other than inhibiting bone resorption, BPs have many other activities such as inhibiting cancer cell metastases, apoptosis and proliferation, reducing pain, altering cytokine and growth factor expression, and inhibiting angiogenesis and matrix metalloproteinase activity.

Clinical Use and Side Effects in Humans

  • In humans, BPs have been pivotal in treating osteoporosis and metastatic breast and prostate cancer.
  • However, there are associated risks, including acute-phase reactions, esophagitis, gastritis, and links to very rare conditions like atypical femoral fractures and osteonecrosis of the jaw.

Use In Horses

  • Despite the well-documented benefits of BPs in human medicine, research is still ongoing regarding their effects in equines.
  • Currently, only non-nitrogen-containing BPs are approved by the FDA for use in horses, specifically for treating navicular syndrome.
  • The article aims to provide insights on the strengths, weaknesses and potential future use of BPs in equine veterinary medicine.

Cite This Article

APA
Mitchell A, Watts AE, Ebetino FH, Suva LJ. (2019). Bisphosphonate use in the horse: what is good and what is not? BMC Vet Res, 15(1), 211. https://doi.org/10.1186/s12917-019-1966-x

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 15
Issue: 1
Pages: 211

Researcher Affiliations

Mitchell, Alexis
  • Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, College Station, TX, USA.
Watts, Ashlee E
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Ebetino, Frank H
  • Department of Chemistry, University of Rochester, Rochester, NY, USA.
Suva, Larry J
  • Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, College Station, TX, USA. lsuva@cvm.tamu.edu.

MeSH Terms

  • Animals
  • Bone Diseases / drug therapy
  • Bone Diseases / veterinary
  • Bone and Bones / drug effects
  • Diphosphonates / therapeutic use
  • Forecasting
  • Horse Diseases / drug therapy
  • Horses
  • Humans
  • Lameness, Animal / drug therapy
  • Osteochondrosis / drug therapy
  • Osteochondrosis / veterinary
  • Osteoclasts / drug effects

Grant Funding

  • R01 CA166060 / NCI NIH HHS

Conflict of Interest Statement

The authors declare that they have no competing interest.

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Citations

This article has been cited 7 times.
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