Bisphosphonates continue to be a topic of concern in the racing world, most notably raised by a report of a positive test from John Salder trainee Flagstaff, but researchers are still learning about how to find and regulate the drugs in horses. Although two drugs, sold under the trade names Osphos and Tildren, were approved by the Food and Drug Administration for use in horses several years ago, research into the drugs' action in young horses and the length of its life inside the equine body is still catching up. (FDA-mandated testing is focused on safety and efficacy of a new drug, not necessarily the ability of a state racing commission to detect it in a post-race sample from a young racehorse.)
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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