Bisphosphonates and Santa Anita

[davew]

It sounds like it can be tested for with a bone biopsy.

[drib]

Originally Posted by davew

It sounds like it can be tested for with a bone biopsy.

I have been puzzled by the current industry information.
(!) We are being told by the drug company, Ky., and Calif officials that bone biopsy results are just not there yet. This despite the fact that the drug has been easily detected in human bones for 20+ years, and I even found a 2011 Canadian study that assayed the drug in equine bones.
(2) The same industry plus sales companies are now offering a blood test supposedly good for 28 days, (though Ky Equine Director Mary Scollay says testing can be good for up to 100 days); all this, despite as I have noted, the drug rapidly clears blood and urine, but sticks to bone for possibly years.
(3) In connection with #1, and #2, I have been unable to find a report anywhere of bisphosphonate drug positive in any investigative setting (pre-race; post race; sales ring; autopsy etc.).

i have done some more research. I still cannot understand the failure to release any bone necropsy reports, but it is possible that these investigators are focussing on determining precise drug concentrations, rather than just whether the drug is found at all. Given that any public reveal that bisphosphonate was found in any amount in bones of dead horses would create a firestorm, I am guessing (emphasis just a guess) everyone is hiding behind technical difficulties in titrating exact amounts.
I think i can now understand the blood test talk. All bone undergoes constant microscopic remodeling initiated by osteoclasts which break down bone. Bisphosphonates, as noted, quickly stick to bone, but the normal constant bone rebuilding can result in small amounts of the drug released back in blood where it again is rapidly taken up by bone again. This process is called reattachment, and could explain the time frames discussed for blood testing, though the blood concentrations would be very small. I have been unable to find any reports of positive blood/urine findings so far away from time drug was given. Reattachment would make any legal actions very difficult b/c the drug could be found a long time after it was administered making it impossible to prove the source.

[davew]

It is kind of a mute point if getting the sample is so invasive that horse owners and trainers will not allow it anyway.

[drib]

Originally Posted by davew

It is kind of a mute point if getting the sample is so invasive that horse owners and trainers will not allow it anyway.

Just to clarify there are different samples. The sales companies are referring to samples of blood, and possibly urine, that will be allowed by buyers of babies. Any pre or post race testing would also be blood/urine. Right now, the only bone samples are taken when the dead breakdown animals are autopsied.

[drib]

In examining the CHRB website, I discovered this 47 page list of hundreds of foreign substances which are not allowed.
http://www.chrb.ca.gov/misc_docs/rul...ances_0219.pdf

Note that the bisphosphonates, Tildren (tiludromite disodium) and Osphos (clodronate disodium) are not on the list. I realize that no such list could be all inclusive, but the bisphosphonates have been around for several years, and, even before the recent tumult, had well know pain relieving qualities ("can make a lame horse sound in one day"). I find it amazing these drugs were not on the list, and wonder if post race toxicology even looks for them; of course, this could explain (at least in Calif.) why there has never been a positive. Tough to find a drug if one does not look for it.
i remain unsure that the bisphosphonates could be so overlooked, but, based on years in the business, I do know that, if true, every racetrack vet knows they don't test for it (not saying they all use it), as well as many trainers. Perhaps the CHRB should spend less time on whips, and more time on drugs.

[drib]

Friday the New York State Gaming Commission through Equine Medical Director Dr. Scott Palmer issued the following Advisory Warning on bisphosphonates:

https://www.gaming.ny.gov/pdf/Bispho...%20Warning.pdf

A few takeaways; it appears that up till last Friday, just like with the CHRB, NY did not have the bisphosphonates listed as a restricted (to older horses) or prohibited drug. I am highly doubtful they have ever tested for this drug; in addition, given that the pain relieving effects (never mind the bone action) of this drug have been known for many years, what took the authorities so long to identify a potential problem? Is this an indication of the competence of drug testing officials in the sport? Note that the only references Dr. Palmer provided are human studies from more than 10 years ago. As I have noted in older posts, the equine bisphosphonates were not even on the USA market at the time of these studies, and there exists a whole body of work on the equine effects of the drug. Strange that Dr. Palmer just cites old human studies; seems rather rushed shoddy scholarship.
I would ask Dr. Palmer whether NY State has been testing for bisphosphonates in post race toxicology; if the answer is yes, I would further ask if there has ever been a reported positive. Given the biology/biochemistry of the drug, I suspect the answer is no, and everyone is on the honor system.
The announced NY penalties for using bisphosphonates are draconian: "Thoroughbred horse owners, trainers and/or veterinarians who are responsible for causing or failing to guard against an administration of a bisphosphonate to a racehorse less than four years old will be investigated for a violation of 9 NYCRR § 4043.12(c) for which a fine of $25,000 may be imposed and the person’s occupational license shall be revoked." Note also that NY is following the British model, by permanently banning any affected horses. I am no legal expert, but trainers whose horses test positive for some really strong stuff don't usually face $25k fines and loss of license w/o a long history of priors.
I do support such penalties, but the NY authorities reveal ignorance of bisphosphonate drug qualities (maybe they should have checked up to date references). As discussed in this thread the drug lasts many months, and probably years (10 years in rats; my Canadian study stopped after one year, and bone levels were unchanged from day 1) after given to horses, thus it would be impossible to assign the usual absolute insurer rule to trainers, Example: A 2 yr old is given the drug in Jan (to make his bone Xrays look better), and sold in July. The new trainer/owner etc. has no knowledge of the drug, but it is in the bones. Should bisphosphonates be discovered, how can the current people involved with the horse be held liable? Given the biology/biochemistry involved, I cannot believe these penalties could withstand legal challenge.
There is a possible alternative narrative: All these officials in several states are not incompetent at all, but they are faced with a desperate situation. The drug cannot be found in usual testing, but they cannot admit the vulnerability, so they release a torrent of smoke and mirrors to frighten potential users (example all the talk of a 28 day window in blood testing, when the same biochemical characteristics that would limit post race testing above would apply). To clarify the situation, the results of bone biopsy on the dead horses would be valuable, but we hear nothing.

[foregoforever]

Thanks for all your posts on this, Drib.

There have been many drug "crises" over the years -- steroids, cobra venom, cobalt, etc. -- but this one is bothering me much more.

I'm not a doctor or vet, but it doesn't take much smarts to read the description of how these drugs work and know that they are extremely risky for young horses. You're screwing with bone growth, for God's sake! Any vet that administered these drugs to young horses should lose his/her license. They really should have their legs broken as well.

I'm not ready to join PETA, but I can no longer muster up arguments with a lot of what they're saying, particularly about medications.

[drib]

On Friday, the NY Gaming Commission issued new severe measures to combat bisphosphonate use: immediate license revocation/ $25k fine; permanent banning of horse (BTW other than some infectious crisis, has there ever been such a blanket, automatic ban of race horses?). This class of drugs biologically represents a threat to racing; now let's watch the CHRB which, currently, does not even have bisphosphonates on their list of banned drugs. I would expect emergency steps to follow NY's lead, given the CHRB has acted against whips and lasix, which have zero to do with the breakdown crisis. A failure to immediately harshly deal with this drug could be a sign that they may be hiding the toxicology results of necropsy bone biopsy, and are desperate to keep bisphosphonates out of the news.

[drib]

I continue to be surprised that regulators in California, and most likely many other states, have failed to include bisphosphonates on a list of prohibited drugs. Here is a notification from FEI, a European Dressage organization, which, last year, listed Tildren and Osphos as controlled substances on their Equine Prohibited Substances List .http://www.eurodressage.com/2018/12/...isphosphonates
From the statement "Bisphosphonates are substances that can be used in horses to treat certain bone diseases e.g. osteoarthritis and navicular syndrome. They act by preventing bone degradation and provide very effective analgesia. Inappropriate use of these substances can prevent bone repair and lead to an increased risk of fractures and catastrophic injuries." My question to California regulators: Why have you never dealt with this drug?

[Jeff P]

There were two non-lasix related medication items that were distributed as part of the meeting agenda package for the the March 28, 2019 public CHRB meeting.

From the CHRB website --

March 28, 2019 CHRB meeting agenda package:
http://www.chrb.ca.gov/Board/board_p...s/Mar-2019.pdf

11. Discussion and action by the Board regarding the proposal to suspend one or more medications authorized in CHRB Rule 1844, Authorized Medication, for all horses participating in a horse race meeting at Santa Anita Park and/or Golden Gate Fields pursuant to CHRB Rule 1844.1, Suspension of Authorized Medication.

12. Discussion and action by the Board regarding the proposal to suspend one or more medications authorized in CHRB Rule 1844, Authorized Medication, for all horses participating in all licensed horse race meetings for 12 months pursuant to CHRB Rule 1844.1, Suspension of Authorized Medication.

SUMMARY OF CHRB ACTIONS AND DISCUSSIONS 3-28-19:
http://www.chrb.ca.gov/press_release...ss_release.pdf

The Board immediately suspended authorization of thresholds for steroidal and nonsteroidal anti-inflammatory medications in post-race samples collected at Santa AnitaPark and Golden Gate Fields. This means veterinarians and trainers will need to stop the administration of those medicines well before the horse races, so that the medications will have cleared the horse’s system. This applies to phenylbutazone (commonly known as bute), flunixin, ketoprofen, corticosteroids, and several other medications. The Official Veterinarians and Equine Medical Director are working closely with practicing veterinarians to provide information on withdrawal times for those medications based on international recommendations and other sources. The Board will consider extending these restrictions to other racetracks in California at the April meeting.

Bute, flunixin, ketoprofen, and corticosteroids are mentioned by name.

To the best of my knowledge, no specific mention (yet) from the CHRB about bisphosphonates.

I find that odd (given all the media attention) about bisphosphonates over the past few weeks.



-jp

.

[drib]

I have been puzzled about use of a 28 day limit in the detection of bisphosphonates from blood samples. The sales company are using this time frame. As I have earlier discussed, the drug quickly clears blood, with 5.5 hour half life, and adheres to bone. I postulated that the 28 day limit was caused by reattachment, when the drug gets released back into blood as part of active bone remodeling. Well, I have been able to find a BHA communication sent out in 2017, one year before bisphosphonates were completely banned for horses under the age of 3.5 years.
https://www.britishhorseracing.com/w...nates-2017.pdf

Note the following statements: "Due to their complex nature and action, the excretion of bisphosphonates may be unpredictable,leading to considerable variation in excretion times. This variability may be increased when bisphosphonates are administered to horses with on-going musculoskeletal disease process,including the possibility that bisphosphonates may be released from bone at a period remote from initial administration. As such, it cannot be guaranteed that future musculoskeletal disease processes will not result in an Adverse Analytical Finding.As a guide, the BHA are aware of data fr om studies in normal horses which indicate that if a single dose of Tildren® (CEVA) at 1 mg/kg were administered intravenously, the Detection Time would be unlikely to exceed the Stand-Down period. A discussion between the Responsible Person and their veterinary surgeon is essential when considering administration of any medication which is a Prohibited Substance on race day."

Here, again, is reference to the 28 day time frame. Though I have been unable to find such a study, I assume it comes from the drug maker. The study was on healthy animals, which raises issues b/c in practice, the bisphosphonates are used on diseased bones, which would mean a different rate of bone turnover, and as the BHA notes, the drug could appear at any time in blood; of course, I again note that i cannot find a reported drug positive anywhere in the world.

[jay68802]

Originally Posted by Jeff P

To the best of my knowledge, no specific mention (yet) from the CHRB about bisphosphonates.

I find that odd (given all the media attention) about bisphosphonates over the past few weeks.



-jp

.

The Medication and Safety Committee will be discussing bisphosphonates on April 17th, the day before the next CHRB meeting. The discussion will be a topic in that meeting.

[drib]

Originally Posted by jay68802

The Medication and Safety Committee will be discussing bisphosphonates on April 17th, the day before the next CHRB meeting. The discussion will be a topic in that meeting.

Thx for the heads up. Here is the CHRB announcement: http://www.chrb.ca.gov/Board/committ...r-2018MSWC.pdf

Perhaps someone should ask (1) Has Calif. toxicology been testing for this drug, and if yes, have there been any positives; (2) Have bisphosphonates been found in bone chip analysis of the dead SA horses? If the answer is non responsive, ask why such a delay when proven assay methods were described in a Canadian paper in 2011. Here, again, is the study:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062923/

[Jeff P]

Originally Posted by jay68802

The Medication and Safety Committee will be discussing bisphosphonates on April 17th, the day before the next CHRB meeting. The discussion will be a topic in that meeting.

Thanks for the heads up.


-jp

.

[clicknow]

Originally Posted by drib

IPerhaps the CHRB should spend less time on whips, and more time on drugs.

I think it is generally understood that the race track is sort of a testing ground for meds on horses due to good record keeping, regular blood testing and physical exams, in groups of similarly aged horses, all involved in same sport, swift necropsy programs, etc.

This is how we found out about Thyro-L's problematic cardiac side effects in younger horses.