Study to explore whether a drug combination is harming horse bone health

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Horse racing at Golden Gate Fields, Albany, California. Photo: Noah Salzman CC BY-SA 4.0, via Wikimedia Commons
Horse racing at Golden Gate Fields, Albany, California. Photo: Noah Salzman CC BY-SA 4.0, via Wikimedia Commons

A major US study will explore the effects of a combination of two drugs that may be contributing to catastrophic injuries and cardiac issues in racehorses.

Researchers at the University of Pennsylvania’s New Bolton Center, part of the School of Veterinary Medicine, will carry out a multidisciplinary study exploring combined usage of furosemide, commonly known as Lasix, and bisphosphonates in horses.

It will be the first comprehensive analysis of the two drugs that, when used concurrently could be capable of diminishing bone integrity and compromising cardiac function in racehorses. These effects have the potential to contribute to catastrophic injuries on the racetrack.

“The beauty of this study is that it will use a multi-disciplinary approach to assess the interaction between these two drugs that we know are administered to racehorses,” says Dr Mary Robinson, assistant professor of veterinary pharmacology and director of the Equine Pharmacology Laboratory at the New Bolton Center.

“By coupling our state-of-the-art imaging technologies with the scope of expertise among the other investigators on this project, we will be able to produce solid, unbiased data that will address some of the unknowns surrounding the use of these medications.”

Nearly 85 percent of racehorses in the United States receive Lasix as a preventive therapy for a condition called exercise-induced pulmonary hemorrhage (EPIH), or bleeding into the lungs.

Also used in human medicine to treat heart conditions, the drug is known to cause a short-term loss of calcium and increase the risk of fractures in human patients.

But because horses can quickly recover from a calcium deficit, Lasix alone is unlikely to be the root cause for catastrophic, racing-related breakdowns which, according to The Jockey Club Equine Injury Database, occur at a rate of about 1.6 per 1000 starts.

A team comprised of 13 researchers from the vet school will explore the largely unknown effects of a class of drugs called bisphosphonates, particularly when being used with Lasix.

Intended to preserve the integrity of bone, bisphosphonates are commonly used in elderly patients to treat osteoporosis. When administered to young, growing animals, however, the drug may have adverse effects by preventing bone from properly adapting to the forces applied during training – such as those experienced when a horse is at a gallop.

Because bisphosphonates can linger in the bone for at least one year after the administration of a single dose, there is a heightened chance for interaction with Lasix in horses who are undergoing training.

Bisphosphonates have also been associated with increased risks of heart conditions in humans, including atrial fibrillation, ventricular arrhythmias, and alterations in heart rate variability.

Dr Mathieu Spriet
Dr Mathieu Spriet

The research team will cross-examine other facets related to the use of these substances in racehorses, including pioneering new understandings of advanced imaging systems such as New Bolton Center’s standing robotic computed tomography (CT) and, in collaboration with Dr Mathieu Spriet, from the University of California, Davis, a new standing positron emission tomography (PET) system.

The system, which is identical to the one already in place at Santa Anita Park, will make the New Bolton Center the second veterinary hospital in the world to implement the use of an equine PET scanner.

“This amazing imaging technology is going to be really instrumental in helping us assess the effects – or lack thereof – of these drugs on the bone,” Robinson says.

“It is the most sensitive technique that we have, from an imaging perspective, to look in detail at a horse’s legs and see what’s going on metabolically.”

PET is the most recent advance in diagnostic imaging. It is being developed in California and, when combined with CT, provides information on bone activity and structure. In these three images of the same fetlock from different aspects, the orange spots indicate increased activity in the proximal sesamoid bone, which is a potential precursor to more serious injury.
PET is the most recent advance in diagnostic imaging. It is being developed in California and, when combined with CT, provides information on bone activity and structure. In these three images of the same fetlock from different aspects, the orange spots indicate increased activity in the proximal sesamoid bone, which is a potential precursor to more serious injury. © Dr M Spriet, University of California, Davis

The New Bolton Center’s Kathryn Wulster says the technology will enable researchers to definitively note any changes in bone turnover in areas as precise as two square millimeters.

“But the real beauty of using both the PET scan and our robotic CT system in tandem is that we can confidently identify any present morphologic or shape abnormalities within the bone that we know could predispose a horse to fracture,” Wulster says.

“Together, they’re going to give us a remarkable amount of information about what is or isn’t going on in these horses.”

The research team will also be accumulating findings into an innovative, data-driven platform that will be invaluable to objectively assess national trends in racehorse related injuries.

Biomarkers explored

Researchers at the vet school will also explore Extracellular Vesicle Cores (EVs) in blood or other samples to detect illicit use of bisphosphonates, which are presently undetectable in the blood of a horse after 30 days.

EVs are membrane-enclosed nanoparticles released from all cell types and play an integral role in intercellular communication. Because they possess tissue-specific characteristics representative of the cells in which they came from, they hold the potential to provide non-invasive, rapid diagnostic solutions to test for the presence of illegitimate drug use.

Dr Andrew Hoffman, dean of Veterinary Medicine and principal investigator of the EV Core Facility, describes the field of EV research as a vastly promising and explosive area of study.

“By harnessing the unique communicative power of EVs, we hope to redefine how we can utilize blood samples in order to proactively safeguard the health and well-being of these tremendous athletes,” he says.

“Beyond detecting illegitimate substance use, these biomarkers also offer the means of identifying otherwise indiscernible, but significant, changes in the horse’s biological health that could serve as warning signs of an increased risk for catastrophic injury.”

Robinson adds: “Our hope is to eventually harness the information carried in these vesicles to develop a hand-held, stall-side diagnostic tool that could be used on race day to make sure horses are healthy enough to compete safely, as well as by trainers in the field to continuously evaluate any changes in their horse’s well-being, and when additional veterinary care may be needed.”

The study is expected to take two years to complete.

It will, says Robinson, provide the most comprehensive data available to assess if the use of these substances may or may not be contributing to catastrophic injuries on the track.

“At the end of the day, we’re dedicated to ensuring we are doing everything in our power to provide owners, breeders, and trainers with sound, unbiased insights to keep their horses safe.”

Robinson is an assistant professor of veterinary pharmacology and director of the Equine Pharmacology Laboratory at the University of Pennsylvania School of Veterinary Medicine.

Additional investigators on the study include Dr Kyla Ortved, Dr Cristobal Navas de Solis, Dr Claire Underwood, Dr Virginia Reef, Dr Darko Stefanovski, Dr Rachel Derita, Dr Joanne Haughan, Dr Youwen You, Dr Jinwen Chen and Dr Zibin Jiang, all with the university’s veterinary school.

This study is supported in part by Roy and Gretchen Jackson, George and Julia Strawbridge, and the Pennsylvania State Horse Racing Commission.

Another biphosphonates study

In other news, the board the Racing Medication and Testing Consortium (RMTC) has approved the funding of an unrelated study on bisphosphonates through its Tactical Research Grant Program. The research will be conducted at Cornell University under the direction of Dr Heidi Reesink.

“This study is an important first step in answering questions about the prevalence and effect of bisphosphonates in the training and racing population, so that we can refine our strategies in protecting racehorse bone health,” RMTC executive director Dr Mary Scollay says.

The RMTC consists of 23 racing industry stakeholders and organizations that represent Thoroughbred, Standardbred, American Quarter Horse and Arabian racing.

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