Bisphosphonates Use in Racehorses

Compiled by Nancy Brannon, Ph.D.

Finding the cause of horseracing deaths at Santa Anita, and other racetracks, often focuses on the use of performance-enhancing drugs. Joe Drape wrote in The New York Times, June 26, 2019: “Experts have long considered drugs a leading cause of horse deaths. Not only do they dull pain and mask injuries, letting at-risk horses run when they should not, but they make horses unnaturally stronger and faster, increasing stress on their limbs.”

The Jockey Club collects fatality data from participating racetracks in its Equine Injury Database, but doesn’t include the cause or nature of the injury.  http://jockeyclub.com/default.asp?section=Advocacy&area=11. [Note that the two tracks in the mid-south, Kentucky Downs and Oaklawn, do not report to the EID.]

Daniel Ross, of Thoroughbred Racing Commentary (TRC), explored the use of bisphosphonates in racehorses, drugs that are used to treat degenerative bone disease in humans. “The potential consequences from misuse of these drugs in racehorses is causing concern among respected veterinarians and regulators in the industry,” Ross writes. “There is much that is still unknown about the way that bisphosphonates affect the physiology of the racehorse, with the bulk of the research done on humans and animals other than horses.”

“It’s a big concern industry wide,” Ross quoted Jeff Blea, a Santa Anita-based veterinarian, one of a number of prominent veterinarians in recent years to have dug into the effects of bisphosphonates in racehorses.

In 2014 the Food and Drug Administration (FDA) approved two bisphosphonates — Tiludronate (Tildren) and Clodronate (Osphos) — for use in horses over the age of four. Sue Stover, a professor of veterinary anatomy at the UC Davis School of Veterinary Medicine, explained it in an email to TRC, “Bones are continually renewing themselves throughout life to prevent fatigue failure [bone fracture].”

Ross explains further: “In order for bones to keep remodeling and generating new bone cells, they need to shed the old dead bone tissue, which is where osteoclasts and osteoblasts come in. Osteoclasts are cells that help dissolve, break down and absorb damaged or weakened bone tissue. This process is called resorption. Osteoblasts are cells integral to the growth of new bone. They help to fill the tiny little holes left when cells have died, and where resorption has occurred. Bisphosphonates inhibit the work that osteoclasts do, thereby preventing the breakdown of bone tissue (hence why they’re used to treat navicular disease).”

However, since bisphosophonates inhibit the functions of osteoclasts, old dead bone cells aren’t destroyed, but stay where they are. The dead tissue has lost all its former elasticity, but has the effect of making the diagnosis of bone conditions difficult with x-rays, since the dead bone material can give the impression of everything appearing okay, explained Rick Arthur California Horse Racing Board equine medical director. “The concern is bisphosphonates make bone look good on radiographs,” he said, “when in fact, the bone is weakened.”

“Bone has to undergo resorption before it gets stronger,” said Arthur. “It’s a normal process, and, if you inhibit that process, you’re inhibiting the ability of the bone to strengthen and to become strong enough to withstand the rigors of racing and training.”

Natalie Voss reported that in 2018, surgeon Dr. Larry Bramlage issued a warning at Rood and Riddle’s annual Client Education Seminar about misuse of bisphosphonates, “putting racehorses at serious, long-term risk of injury or delayed healing from injury.”

Voss explains use of the drugs: “Bisphosphonates (sold commercially as Osphos and Tildren) are FDA-approved in horses four years old and up, and are not approved for use in mares who are pregnant or lactating. The reason for those restrictions is unanswered questions about potential side effects. Bisphosphonates do their work by reducing the action of cells called osteoclasts, which clear away damaged bone and make way for osteoblasts to lay down new bone. In a young equine skeleton, this could disrupt the growth cycle.”

“A forum discussion at the 2018 American Association of Equine Practitioners annual convention yielded mixed opinions on the drugs.” …However, “one Florida practitioner …told the Paulick Report that a well-known vet group had seen a ten-fold increase in catastrophic breakdown and long bone stress fractures in 2-year-olds in training since the approval of bisphosphonates for use in horses.”

Voss continued: “Many have questioned whether bisphosphonates could play a role in the recent spike in equine fatalities at Santa Anita. Bramlage told the Paulick Report he doubts this, since there would be no reason to expect Santa Anita's population would have been more exposed to the drugs than any other.” However, “the problem is lack of information about how many veterinarians are actually using bisphosphonates off-label in young horses, when they're using it, or how many doses horses are getting,” Voss wrote.

The primary approved use for the drug is in navicular syndrome and Bramlage said he has found them useful in retiring horses who are older and can have arthritic fetlock joints.

Dr. Jonathan McLellan, researcher and practitioner with Florida Equine Veterinary Associates, “wants to see veterinarians take bisphosphonates out of trainers’ hands,” Voss wrote.

In the Lexington Herald Leader, Janet Patton looked into the deaths of horses at Santa Anita, and horse fatalities at Kentucky’s tracks that nearly doubled in 2018. “At the February meeting of the Kentucky Horse Racing Commission, equine medical director Dr. Mary Scollay outlined the problem. She had no clear answer as to why there were more horse deaths, but she noted one shift: the horses that died were younger – 2 and 3-year-olds rather than 3 to 4-year-olds. “Scollay wondered if a relatively new class of drugs could be masking vulnerability in bones (and the deaths in Kentucky and in California are almost all musculoskeletal) that is contributing to the wave of deaths.

“Bisphosphonates are osteoporosis medications approved for use in horses 4 or older to treat a bone disease called navicular disease. They work not by building new bone but by killing off the cells, called osteoclasts, that clear away bone with microdamage. In people with serious disorders such as osteoporosis, this helps because it prevents the hollowing of bones.

“Last April, two vets presented concerns to the ARCI annual meeting about widespread off-label usage of these drugs in racehorses and young horses. Dr. Sue Stover of the University of California-Davis veterinary college said that bisphosphonates had been regarded as ‘a silver bullet’ for myriad bone issues.

“Instead that might have created what has been called a ticking time bomb in some racehorses. The drugs are suspected of creating bones that look sound on X-rays but aren’t capable of normal healing.”

Patton also turns to “equine orthopedic surgeon Dr. Larry Bramlage of Rood & Riddle, who said that when the drugs, sold under the name Tildren and Osphos, first became available, he was concerned they would create the potential for catastrophic breakdowns. Instead, what he began to see was horses taking months longer to heal from routine injuries. He thinks that a ban on the use of bisphosphonates in young horses is a smart move, but is skeptical the drugs are responsible for the rash of breakdowns that racing has seen.”

Marty Irby told us, “The Senate version [of the Horseracing Integrity Act of 2019], led by Sens. Gillibrand and McSally, address the bisphosphonates, whereas the House bill doesn’t. [Bisphosphonates are covered in Sec. 7, Unfair or deceptive acts or practices.] The Senators wanted to make sure to cover that issue.” Read the full Senate bill here: https://www.congress.gov/bill/116th-congress/senate-bill/1820/text

Read a summary of the House bill here: https://www.congress.gov/bill/116th-congress/house-bill/1754

 

Sources:

Drape, Joe and Corina Knoll. 2019. “Why So Many Horses Have Died at Santa Anita.” The New York Times. June 26. https://www.nytimes.com/2019/06/26/sports/santa-anita-horse-deaths.html

Gill, Amy M., Ph.D. “Bicarbonate Loading Horses.” 2018. Equi-Force. May 12. https://www.equiforce.com/bicarbonate-loading-horses/

Patton, Janet. 2019. “Is an obscure osteoporosis drug a ticking time bomb for horse racing?” Lexington Herald Leader. April 4. https://www.kentucky.com/sports/horses/article228435554.html

Ross, Daniel. 2017. “The bone disease treatment drugs that may be putting young horses at risk.” Thoroughbred Racing Commentary. October 3. https://www.thoroughbredracing.com/articles/bone-disease-treatment-drugs-may-be-putting-young-horses-risk/

Voss, Natalie. 2019. “Bisphosphonates: What We Know About Off-Label Use, And What One Drug Company Is Doing About It.” Paulick Report. March 26.

Voss, Natalie. 2018. Paulick Report. “Bramlage: ‘Price To Pay’ For Bisphosphonate Use Is Delayed Healing.” Paulick Report. March 1. https://www.paulickreport.com/horse-care-category/bramlage-price-pay-bisphosphonate-use-delayed-healing/

 

 

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