“Drs. Shell and Hippie vehemently deny any violation of the veterinary rules as posted pursuant to HISA,” said Drew Mollica by phone Saturday. “We look forward an immediate hearing so that all of the facts may be explored and their good names and reputations restored. Dr. Shell's practice is known for its integrity, and any substances in his possession were used properly, and were in his possession pursuant to the rules.”

Covered horses are defined by the Horseracing Integrity and Safety Authority “any Thoroughbred horse, or any other horse made subject to the Act by election of the applicable State Racing Commission or the breed governing organization for such horse under section 3054(l), during the period: (A) beginning on the date of the horse's first Timed and Reported Workout at a Racetrack that participates in Covered Horseraces or at a training facility; and (B) ending on the date on which the horse is deemed retired.”

Dr. Shell's three-person practice, for which Dr. Hippie works, covers a HISA-covered area in Ohio—Thistledown–as well as West Virginia, where HISA is not in effect.

Drs. Shell and Hippie are charged with violating Rule 3214 (a), which reads:

Rule 3214. Other Anti-Doping Rule Violations Involving Banned Substances or Banned Methods

The following acts and omissions constitute Anti-Doping Rule Violations by the Covered Person(s) in question:

(a) Possession of a Banned Substance or a Banned Method, unless there is compelling justification for such Possession.

Mollica said that there is no violation of the rules for veterinarians possessing the substances to treat non-covered horses on farms or in other situations. “Both Dr. Shell and Hippie will show unequivocally that they were using the medication for the health and safety of non-covered horses. There's not one allegation of any banned substance being used on a covered horse.”

Earlier in September, Shell testified in person before a HIWU-related arbitration panel on behalf of trainer Dennis VanMeter, whose horse, Templement, had tested positive for isoxsuprine and phenylbutazone. VanMeter was facing a possible two-year ban as a result of the isoxsuprine positive alone.

At the hearing, it was established that Templement had been placed into one of trainer John Brown's stalls at Thistledown previously occupied by a pony routinely administered Isoxsuprine.

In the ruling, it notes that Shell “credibly testified that he and veterinarians in his practice had prescribed isoxsuprine to Mr. John Brown's pony Bucky for the last five years for a condition with its feet that would make it lame without medication.”

The arbitrator found the positive a likely instance of environmental contamination, and that VanMeter bore “no fault or negligence” for the isoxsuprine positive.

That hearing was on Sept. 12, a little over two weeks before Shell and his associate, Hippie, were allegedly found in possession of isoxsuprine and other banned substances, including bisphosphonates.

Additional reporting by Dan Ross. 

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It is understood these are the first such actions HIWU has taken for possession of bisphosphonates. No post-race or out-of-competition samples have as yet returned positive for bisphosphonates, according to the HIWU rulings web-page.

HIWU is the drug enforcement arm of the Horseracing Integrity and Safety Act (HISA).

In an action dated Sept. 28, the two veterinarians, Scott Shell and Barbara Hippie, have been accused of violating HISA Rule 3214(a), possession of banned substances. Formal hearings on the accusations are pending.

Aside from bisphosphonates, Shell is accused of possessing two other banned substances. One is Gamma Aminobutyric Acid (GABA), an amino acid that can be used as a calming agent. The other is the vasodilator Isoxsuprine, which can be used to treat laminitis and navicular disease.

Hippie is also accused of possessing Sarapin, a pitcher plant extract that can be used in pain relief, Isoxsuprine, and Levothyroxine, a thyroid treatment. All three are banned at all times under HISA.

The TDN emailed both Shell and Hippie Friday afternoon for comment. The story will be updated as necessary. An online search suggests the veterinarians are Ohio-based.

The TDN also contacted HIWU for further details of the complaint. Spokesperson Alexa Ravit wrote in response that the organization is unable to provide any further information regarding the alleged violations beyond what is listed on the website.

Ravit confirmed, however, that the violations were the result of each individual being in possession of the listed banned substances on Sept. 28. “Possession charges may result from searches of locations such as barns, offices, and veterinary trucks,” she wrote.

With brand names like Tildren and Osphos, bisphosphonates are used in older horses to tackle issues like navicular disease. They have also historically been used off-label to treat issues like sore shins in younger horses.

A problematic feature of bisphosphonates is that they can remain in a horse's system for many years after administration, making this a potentially tricky drug to track as horses pass through multiple hands.

Further complicating matters is how a horse administered a bisphosphonate won't necessarily test positive for the drug consistently over time.

Considering the severity of the sanctions for a banned substance positive finding, the slippery issue of bisphosphonates has made many industry stakeholders jittery.

Under HISA's rules, any “Covered Horse” proven to have been administered bisphosphonates will be subject to lifetime ineligibility, and the responsible individual could incur an anti-doping violation sanction.

Prior to HISA's anti-doping and medication control program (ADMC) going into effect earlier this year, HIWU chief of science, Mary Scollay, warned stakeholders to be vigilant about purchasing horses from aboard especially.

“As a condition of sale, I would have the seller attest that the horse has never been treated [with a bisphosphonate] so you have got the ability to turn that horse back and get your money back,” Scollay told an assembled crowd of stakeholders at Santa Anita in March. “It's a civil legal situation, but I think there are ways to protect yourself if needs be.”

Horses already in the racing pipeline may have been administered bisphosphonates in the past without their current connections' knowledge. With that in mind, one stakeholder asked Scollay if HISA's investigative body has the authority to go back over the horse's full medical history, in the event of a positive bisphosphonate test.

Though a young racehorse remains beyond HISA's legal purview until the time of its first official workout, HISA does have subpoena authority, explained Scollay. Ultimately though, as the HISA law is written, the burden of responsibility, she stressed, is placed on the trainer and owners' shoulders.

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But with it has come this other question: What do buyers now need to be aware of when purchasing a horse at the sales or privately?

The question has gained added currency since a recent the Southern California horsemen by representatives from the Horseracing Integrity & Welfare Unit (HIWU), the arm of HISA charged with rolling-out and managing its anti-doping and medication control (ADMC) program.

At that presentation, Mary Scollay, HIWU's chief of science, explained that under the new medication regime, bisphosophonates–a controversial group of drugs used in older horses to tackle issues like navicular disease but also used in younger horses to treat things like sore shins–will be banned from administration in what HISA terms “covered horses.”

(It should be noted that a Thoroughbred becomes a “covered horse” only when it completes its first officially timed and published workout)

“My last two weeks has pretty much been a deep dive into bisphosphonates and how to navigate this stuff,” said Joe Miller, a racing manager and bloodstock advisor, who leans heavily on Europe when scouting for new talent destined for the U.S.

“I actually skipped going to the OBS March sale because I'm so focused on how we're going to be moving forward in navigating these purchases,” Miller added.

For all sorts of reasons, bisphosphonates pose a slippery set of problems for regulators and horsemen alike. Once administered, they can stay in a horse's system for years. Horses given a bisphosphonate won't necessarily test positive for the drug consistently over time either, with a positive finding more likely during periods of bone remodeling, which would release the drug into the horse's system.

Punitive consequences for a positive bisphosphonate finding can be steep. A trainer faces a possible two-year suspension for a first-time bisphosphonate violation, while the horse could be subject to lifetime ineligibility from competition.

Joe Miller | Tattersalls

HIWU published a notice to the industry on March 10 regarding the use of bisphosphonates under the ADMC program, explaining how only proven administration of a bisphosphonate to a covered horse after the March 27th implementation date would be deemed an actionable violation.      Furthermore, HIWU explained that it would not pursue disciplinary action for a positive bisphosphonate finding against a covered horse and its connections, provided those connections can share with HIWU documentation–such as medical records or a positive test result–proving administration or presence of bisphosphonates prior to the ADMC program implementation date.

“In accordance with HISA's requirements for Covered Horses, all medical records, including any relevant test results, must be uploaded to the HISA portal. Additionally, due to the variability of bisphosphonate detection through laboratory analysis, all bisphosphonate findings detected under the ADMC Program will undergo thorough review regardless of the alleged timing of administration,” the notice added.

This still leaves some worrying holes for trainers and owners to potentially fall through.

A fear among buyers is that because of the longevity with which bisphosphonates can stay in the system, a recently purchased horse administered bisphosphonates prior to the ADMC launch date–and unbeknownst to the new connections–could still land them in regulatory hot water.

Furthermore, buyers like Miller are concerned about purchasing horses from international jurisdictions where bisphosphonates are still permitted.

“Since private sales are subject to individual contracts, it is up to the buyer and seller to formalize provisions for bisphosphonates testing and conditions of sale to protect all parties,” wrote Scollay, in response to a list of questions.

Miller hasn't made any international purchases since last October, he said, but he expects that to change in the next few weeks. When Miller does once again plunder foreign shores, “we can definitely do a blood screen for Osphos and Tildren,” he said, singling out two of the more commonly-used bisphosphonates. “I'm hoping we can do a urine screening as well.”

Indeed, urine samples are deemed more accurate than blood screens at detecting bisphosphonates administered longer in advance due to typically higher concentrations in urine of most substances than in the blood.

Though HIWU has stated it will conduct a thorough review in the event of a bisphosphonate positive, “If you come up with a trace amount of bisphosphonate in a post-race urine sample, how is that going to be dealt with?” asked Miller. “Is a horse going to be able to compete while the review is being conducted?”

According to HIWU spokesperson, Alexa Ravit, “HIWU will not just automatically issue a suspension for a Covered Horse or Covered Person upon receiving a positive finding for bisphosphonates.”

Fasig-Tipton is one of the major U.S. sales companies to have taken steps in recent years to limit drug use in the horses that pass through their rings, including offering bisphosphonate testing as a condition of sale for horses younger than four.

If the sale horse tests positive for bisphosphonates, a buyer has the right, within 24 hours of notification, to rescind the sale. In Fasig-Tipton's case, a bisphosphonates test costs $500.

“As with all these drug tests that have come along, it's usually because there has been a shift in the market,” said Bayne Welker, executive vice president of Fasig-Tipton. “That's usually what drives us to make these offerings.”

And as a result of HISA, “I'll probably take the limitations off of the racing age horses,” explained Welker, pointing to the condition of sale bisphosphonate test.

Indeed, Scollay stressed how “buyers should consult sales companies, as applicable, to verify the bisphosphonates testing available as well as the conditions of sale should a purchased horse test positive for bisphosphonates.”

Which leads to concerns over the use of other potentially problematic drugs, especially in horses-in-training purchases.

Major sales companies have moved in recent years to restrict the use in sales horses of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and bronchodilators, including Clenbuterol. Welker explained that HISA's new ADMC program won't change what condition of sale tests Fasig-Tipton offers for these particular substances.

Perhaps the biggest concern, explained Scollay, would be if the horse has been administered a banned substance that may linger in the horse for an extended period and show up in testing conducted under HISA, with anabolic steroids singled out for concern alongside bisphosphonates.

Scollay recommends that both buyers and sellers refer to HIWU's “Banned List,” which are the substances not permitted to be in a horse at any time once it falls under HISA's jurisdiction.

According to Miller, none of the drugs listed on HIWU's banned substances list cause him particular concern. “I only buy horses off people that we trust,” he said.

Furthermore, Miller said he will continue his current practice of performing a full blood screening of a horse pre-purchase.

Dr. Mary Scollay | The Jockey Club

“We typically test for steroids, any non-steroidal anti-inflammatories,” said Miller. “We just want to make sure when we do a soundness exam on a horse, we want to make sure they haven't been given anything.”

In regards private testing, however, there is an important distinction for stakeholders moving forward.

HIWU has contracted six labs around the country to conduct its testing program:

The Ohio Department of Agriculture's Analytical Toxicology Laboratory; the Animal Forensic Toxicology Laboratory at the University of Illinois-Chicago; Industrial Laboratories in Denver, Colo.; Kenneth L. Maddy Equine Analytical Chemistry Laboratory at the University of California-Davis; Pennsylvania Department of Agriculture's Pennsylvania Equine Toxicology and Research Laboratory; and University of Kentucky Equine Analytical Chemistry Laboratory.

Trainers and owners can ask HIWU to conduct clearance testing on a horse–for a fee–provided there is a reported administration history of a particular substance. Clearance testing though HIWU will be conducted at these six labs.

But these same HIWU-affiliated labs are prohibited by contract from testing any covered racehorses from private clients, explained Jeff Blea, California Horse Racing Board equine medical director.

And does Blea have any broader advice for industry stakeholders looking to close a sale after Monday?

“Any purchase of a horse as a buyer, you should have a conversation with your veterinarian as to what your concerns are and what your risk tolerance is relative to drug testing as a condition of sale,” Blea replied.

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In advance of the anticipated effective date of HISA's Anti-Doping and Medication Control (ADMC) Program March 27, the Horseracing Integrity & Welfare Unit (HIWU) calls the Thoroughbred industry's attention to regulations regarding the presence and use of bisphosphonates in covered horses.

Bisphosphonates are a class of medication prescribed for managing clinical signs associated with navicular syndrome in horses 4-years-old or above. They also have a history of extra-label use in younger horses. Bisphosphonates may be detected in samples from treated horses for months to years after administration.

The ADMC Program regulations categorize bisphosphonates as a Banned Substance, meaning that they are prohibited from being administered to, or present in, covered horses at any time. Covered horses that test positive for bisphosphonates under the ADMC Program are subject to lifetime ineligibility, and associated covered persons may incur an Anti-Doping Rule Violation.

Given the prolonged detection period for bisphosphonates and the fact that their use is permitted in other racing jurisdictions internationally:

HIWU will not pursue disciplinary action against covered horses or their associated covered person(s) for the presence of bisphosphonates if the covered person(s) can provide documentation (e.g., medical records or a positive test result) to HIWU of the administration or presence of bisphosphonates prior to the implementation date of the ADMC Program. In accordance with HISA's requirements for covered horses, all medical records, including any relevant test results, must be uploaded to the HISA portal. Additionally, due to the variability of bisphosphonate detection through laboratory analysis, all bisphosphonate findings detected under the ADMC Program will undergo thorough review regardless of the alleged timing of administration.

If owners or horsemen have concerns that their horses may have been administered bisphosphonates prior to March 27, including prior to a sale at public auction domestically or internationally, HISA and HIWU advise them to consider bisphosphonate screenings for these horses before the ADMC Program takes effect.

The Horseracing Integrity and Safety Act does not enable HISA's ADMC Program to be enforced retroactively for actions occurring prior to its implementation. The detection of administrations from prior to March 27 that violate respective state rules in effect during that time period will be referred to the relevant state regulatory authorities.

While bisphosphonates continue to be permitted in Thoroughbred racehorses in international jurisdictions, any covered horse proven to have been administered bisphosphonates after the March 27 implementation date will be subject to lifetime ineligibility, and associated covered persons may incur an Anti-Doping Rule Violation.

For questions about the use of bisphosphonates and other substances on the ADMC Prohibited List, stakeholders are encouraged to visit here and reach out to HIWU Chief of Science Dr. Mary Scollay at mscollay@hiwu.org.

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The horse in question–as first reported by the BloodHorse–was GISW sprinter Flagstaff (Speightstown), who was recently retired at the age of seven.

Flagstaff tested positive for the bisphosphonate “clodronate” after finishing second in the 2020 GII Santa Anita Sprint Championship. The Santa Anita stewards subsequently disqualified him, requiring $40,000 in purse monies to be returned, according to a ruling dated June 19 this year.

Bisphosphonates are Food and Drug Administration approved for use in horses 4-year-olds and up for things like osteoarthritis and navicular disease.

But many in the industry have been concerned about the off-label use of these drugs, especially in young horses being prepared for the sales. That's because, rather than strengthening bones as intended, misuse of these drugs could make them weaker, more susceptible to fractures.

These drugs, however, have been notoriously difficult to regulate. Part of the conundrum is that too little is currently known about how long they remain in the horse's system. Bisphosphonates potentially stay in the bone for years.

Too little is also currently known about exactly how they behave for that duration.

As of July 1 last year, the CHRB put into effect a rule broadly prohibiting administration of bisphosphonates to any horse within any CHRB regulated facility. It also prohibits any horse from entering the grounds that has been administered the drug within six months.

Sadler's attorney, Darrell Vienna, stressed that the ruling did not constitute a fine for a medication positive. “If you look at the wording of the actual rule,” he said, “this is not a medication violation.”

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As of Oct. 26, 2021, the New York Drug Testing and Research Program will commence testing of biologic samples for the presence of bisphosphonates. Absent written Commission approval of a valid Therapeutic Use Exemption, detection of bisphosphonate compounds in biologic samples obtained from 2-year-old and 3-year-old Thoroughbred racehorses will be considered by the Commission to be evidence of a violation of 9 NYCRR 4043.12(c) for which a fine of $25,000 and loss of occupational license may be imposed.

Horses testing positive for bisphosphonates will not be permitted to race until such time as they are re-tested and found to be clear of bisphosphonate compounds.

Background

On March 28, 2019, the Office of the Equine Medical Director issued two advisories regarding the use of bisphosphonates. The first advisory recommended that no bisphosphonate be administered to a racehorse that is less than four years old.

The second advisory warned that Thoroughbred horse owners, trainers, and/or veterinarians had a responsibility to guard against an impermissible administration of a bisphosphonate to a racehorse under potential penalty.

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Tiludronate disodium (Tildren) is one of two Food and Drug Administration (FDA)-approved bisphosphonate drugs “For the control of clinical signs associated with navicular syndrome in horses.”

As we know, young Thoroughbred racehorses rarely suffer navicular syndrome, yet tiludronate can be found in the trucks of many racetrack veterinarians. This product is not licensed for anything but navicular syndrome and the safety of this product has not been studied in horses under four years of age. So how and why is tiludronate being used in juvenile racehorses?

How veterinarians use off-label drugs

The FDA grants veterinarians the legal ability to use approved human and animal drugs in an extra-label manner. This means that a drug can be administered to a horse in a way that the product's label does not list.

To prescribe drugs off label, veterinarians need to follow the FDA's requirements for extra-label drug use. For example, the FDA would permit off-label use of a specific medication if:

• There is no animal drug approved for the intended use; or
• There is an animal drug approved for the intended use, but the approved drug does not contain the required active ingredient.

Furosemide (known commercially as Salix or Lasix) provides a good example of off-label drug use in horses. The product information for Salix—which is FDA approved in horses—states, “Salix® is indicated for the treatment of edema, (pulmonary congestion, ascites) associated with cardiac insufficiency and acute noninflammatory tissue edema.” This label clearly does not indicate that the product may be used for prevention of exercise-induced pulmonary hemorrhage. Yet, as we know, furosemide is widely used in competitive horses, including Thoroughbreds, for this purpose.

Similarly, tiludronate can be used off label (i.e., for more than just navicular syndrome) should the veterinarian deem it necessary.

Why use Tiludronate off label?

Tiludronate has “anti-resorption” effects on bone. By binding to osteoclasts, the cells that break down bone, tiludronate minimizes bone turnover. For conditions like navicular syndrome characterized by bone degeneration, stopping this degeneration by decreasing turnover is deemed helpful.

Osteoarthritis (OA), another musculoskeletal condition frequently seen in horses, is characterized by degenerative changes leading to inflammation, pain, and loss of function/retirement. A study published in 2010 demonstrated a beneficial effect of intravenous (IV) tiludronate in the treatment of bone spavin (tarsal osteoarthritis). Specifically, a significant improvement in lameness was appreciated at 60 and 120 days following treatment. That research team concluded, “Tiludronate in combination with controlled exercise offers an alternate medical treatment for bone spavin.”

A similar study found a beneficial effect of IV tiludronate in horses with OA of the thoracic vertebral column.

Most recently, IV tiludronate was evaluated in racehorses with naturally occurring OA of the fetlock (ankle).

The latest research on Tiludronate for OA

The September 2021 edition of the Journal of the American Veterinary Association includes a study of 567 Standardbreds diagnosed with initial-stage OA treated with one of the following:

1. A single joint injection of a combination of the anti-inflammatory corticosteroid triamcinolone acetonide and hyaluronic acid (TA-HA).
2. Intra-articular (within the joint) administration of a polysulfated glycosaminoglycan (PSGAG) once every week for four weeks.
3. IRAP therapy (interleukin-1 receptor antagonist protein) once every week for four treatments.
4. A single intravenous dose of tiludronate.

Clinical responses (i.e., lameness scores, joint flexion tests), radiographic and ultrasonographic findings, and biochemical analyses on blood and synovial fluid samples were compared between the four treatment groups at baseline (Day 0 of the study) and again six months later.

All four treatments resulted in improved lameness scores and flexion test responses. Tiludronate, however, was the only treatment that appeared to inhibit the radiographic progression of OA.

The study also showed that:

• Only TA-HA inhibited inflammatory mediators such as interleukin 1-beta and prostaglandin E;
• Only TA-HA effectively inhibited the degeneration of articular cartilage that occurs with OA. This was demonstrated by a decrease in serum and synovial fluid CTX-II (carboxy-terminal telopeptides of collagen type II), a molecule that increases with progressive articular cartilage degeneration.
• When treated with tiludronate, horses had increased CTX-II (i.e., articular degeneration).
• A decrease in CTX-I (carboxy-terminal telopeptides of collagen type I), a marker of bone degeneration, was observed in horses treated with tiludronate.
• IRAP and PSGAG both had a “significant effect on the clinical manifestations of osteoarthritis.” They did not, however, control radiographic progression and an increase in CTX-II was noted a the 6-month mark, indicating cartilage degeneration.

These data suggest that tiludronate can effectively decrease the progression of OA, potentially by inhibiting subchondral bone remodeling. However, this treatment protocol did not diminish the inflammatory component of OA and may in fact worsen cartilage degeneration in horses with OA.

So, what's the problem?

While research supports using bisphosphonates for navicular syndrome as well as OA, neither condition is terribly common in young racehorses.

“The goal of using bisphosphonates in young horses is to enhance bone formation and to manipulate bone development to hide skeletal pathologies,” said Dr. Jessica Leatherwood, an associate professor of equine science at Texas A&M University. “This attempt to promote early bone maturation and mask potential radiographic flaws may lead to an accumulation of microdamage. This damage could eventually lead to bone failure due to lack of appropriate remodeling.

“Bisphosphonate use in juvenile, exercising horses could result in greater risk of death for horses and humans, and to the eventual elimination of racing and the jobs surrounding the industry.”

According to Leatherwood, the controversy surrounding the off-label use of bisphosphonates is becoming more widespread in the equine industry, especially following the spike in breakdowns and fatalities on the racetrack. She said that while concerns have been raised, there is currently no scientific knowledge of the effects of bisphosphonate utilization in young exercising horses, leaving a critical gap in the knowledge.

To help learn more about the effects of bisphosphonates in young horses, Leatherwood recently received  a $500,000 grant from the U.S. Department of Agriculture's National Institute of Food and Agriculture. Leatherwood's team includes researchers from Texas A&M University, Michigan State University, and Montana State University with expertise in large animal veterinary medicine, pharmacological analysis, bone and cartilage physiology, mechanical testing, and equine endocrinology.

Leatherwood hopes this work “will create new knowledge to improve equine health and welfare and provide meaningful, scientifically-driven recommendations (or warnings) for bisphosphonate use” in juvenile horses.

Dr. Stacey Oke is a seasoned freelance writer, veterinarian, and life-long horse lover. When not researching ways for horses to live longer, healthier lives as athletes and human companions, she practices small animal medicine in New York. A busy mom of three, Stacey also finds time for running, hiking, tap dancing, and dog agility training. 

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Read more about bisphosphonates in our archives here and here.

Dr. Heather Knych, renowned equine pharmacologist at the University of California-Davis, gave an overview of current research on bisphosphonates at the most recent, virtual convention of the American Association of Equine Practitioners (AAEP).

A few takeaways:

• Bisphosphonates may be new to the horse world, where they are FDA-approved for the management of navicular syndrome in older horses, but the drug class has actually been in use in different settings for a couple of centuries. Knych explained that the substance was first used in the detergent industry in the 1800s as a water softener, anti-corrosive or anti-scaling agent. Their action on calcium carbonate made them effective in these settings. They were adapted as therapeutic drugs for human bone conditions in the 1970s.
• While we've most often heard of bisphosphoantes in humans as part of osteoporosis treatment, they've also been used in metastatic bone disorders, and multiple myeloma.
• We know that after an administration, bisphosphonates disappear from blood fairly quickly – their half life is one to two hours in plasma, but they can linger on bone surfaces for months or years.
• Bisphosphonates seem to prefer settling in trabecular bone – bones like skulls and ribs that take less mechanical stress – over cortical bone, like the long bones in limbs. It withdraws from bones based on the amount of turnover in that bone, which can vary depending on age, exercise, and trauma.
• Concentrations of bisphosphonates continues to increase as concentrations of it elsewhere decreases. It can also release from bone back into blood in small amounts and move into other bone surfaces, though we don't know a lot about why and when it does that.
• Knych presented the results of a two-part study led by researchers across multiple universities to learn more about how long bisphosphonates linger in the skeleton. The first part of the project required administration of the two FDA-approved bisphosphonates – Osphos and Tildren – to a total of four horses in university research programs who were already slated for euthanasia for unrelated reasons. Bone samples were taken after euthanasia, which came four days or 30 days after administration in each drug group. Samples from the radial bones showed detectable amounts of both drugs four days after administration, with levels of Tildren being higher in both samples. Thirty days after administration, both drugs could be found in all bones sampled, even right and left molars. Concentrations of both drugs were highest in the tuber coxae (hips).
• In the second phase of the study, researchers tested blood and fluid samples from four horses euthanized due to on-track injuries in California – three whose connections said they'd never had bisphosphonates, and one who had a treatment 18 months prior. The team could find no evidence of bisphosphonates in the three horses with no treatment history. The horse who had been treated 18 months before had no detectable amounts of the drug in serum, urine, or synovial fluid, but did have a detectable level in a sample from the radial bone.
• These results suggest, in line with what veterinarians had expected based on human data, that the drug does linger on the surfaces of bone for considerable periods of time, and lives on different bones in different ways.
• Knych acknowledged that both parts of the study came from extremely small sample sizes, as is often true in academic research with horses, and that further study is needed to better understand how bisphosphonates work in the equine body.

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Flagstaff finished second in that race, and stewards have ordered the purse money to be redistributed.

The bisphosphonate positive was originally announced in late May and trainer John Sadler could still be facing Class 1 drug sanctions, but no hearings have yet been scheduled, according to the DRF report.

Because clodronic acid is not included on the CHRB's current list of prohibited substances, under the regulatory body's rules it automatically falls under the most severe drug category, Class 1. A medication classification proposal working its way through the CHRB's approval process recommends classifying clodronate (clodronic acid) as Class 3, but in the A penalty category.

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