As any racing chemist will tell you, the business of regulating medication use and halting its abuse on the track is a tireless one. During a meeting this week of the Kentucky Equine Drug Research Council, regulators made decisions on how to regulate the use of GABA (gamma aminobutyric acid, also known as Carolina Gold) and cobalt in the state's racehorses, but they also announced the intent to begin studying a new group of drugs: bisphosphonates.
Bisphosphonates are a group of drugs engineered to curb bone loss due to osteoporosis and similar conditions in humans. In 2014, the Food and Drug Administration approved two bisphosphonate drugs—Tildren and Osphos—for use in horses to treat navicular syndrome or chronic aging changes in non-breeding horses over the age of four years.
As with its human use, the treatment comes with some risks; bisphosphonates can cause gastrointestinal or kidney problems, but their analgesic properties make them a godsend for older horses experiencing painful inflammation of the tissues surrounding the navicular bone.
Research published late last year by an international group that included Florida veterinarian Dr. Robert Boswell indicated that 75 percent of horses receiving the treatment showed significant improvement in lameness.
(You may remember several years ago when bisphosphonates made headlines for working a little too well to stabilize bone density, increasing the risk of fractures in human patients; Dr. Mary Scollay, equine medical director for the Kentucky Horse Racing Commission, told council members that the two drugs approved for equine use fall into a different, milder category of bisphosphonates and are not understood to have the same effects when used as directed on the appropriate age group.)
The problem, said Scollay, is that the original purpose of the drug–to maintain and stabilize bone density–can make it dangerous in younger animals.
“Oftentimes, you can't really isolate where the pain is [in navicular disease],” said Scollay. “So if someone is using that same criteria—a poorly-defined, intermittent lameness—and applying that to a 2-year-old in training, they could very well be giving bisphosphonate to relieve pain associated with non-adaptive bone disease. So, the horse that is already at risk of a condylar fracture is at an increased risk of a condylar fracture because there's a drug on board that is preventing the osteoclasts from doing their job.”
Bone is in a constant state of flux between osteoblast cells responsible for building bone, and osteoclast cells that destroy bone. Bisphosphonates are poisonous to osteoclasts, which build bone density. If used in young horses, it can upset the balance of bone remodeling, which takes place in reaction to training. Scollay said there is concern that when used on horses under four years old, the drugs can stall that regeneration process so completely that the bones become brittle and far more likely to break.
Scollay suspects the drugs may be given to relieve bone disease in future sale horses.
“One of the uses that we're hearing is in yearlings for sales prep,” she said. “They get sesamoiditis. This drug could prevent signs of remodeling that would show up on x-ray and in the repository. Those horses aren't at risk of fracture [at that time], but if that drug persists on the surface of bone for two years, that horse is potentially at risk of non-adaptive bone disease through his 3-year-old year.
“When that horse is in training, he may be possessed by an owner who has no knowledge of the previous treatment.”
To further complicate matters, Scollay told the council that bisphosphonates clear the blood within 90 to 120 minutes of administration but are believed to live in the bone's surface for years, making it extremely difficult to test for.
“I can't look anybody in the eye and say, ‘We're going to get a bone sample from your healthy, live horse,'” she said. “That's extremely invasive. We've got to find another way.”
The first order of business for scientists will be to conduct a study on bones of post-necropsy horses to gain an understanding of how common bisphosphonate use is. After that, Scollay said, they'll need to work to quantify the risks associated with its use in young horses. Scollay is part of an international working group established to study the drugs and their impact and will be collaborating with researchers from Hong Kong, Australia, Great Britain, and elsewhere in the United States.
Scollay remained hopeful that hair samples or filings of hooves or teeth could help uncover old bisphosphonate use; she said researchers are also in touch with a metabolomics company to learn if there are other ways to detect the drug.
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