Osphos, one of two bisphosphonates approved by the FDA for use in horses four years of age and older
Bisphosphonates remain a topic of concern in the racing world, particularly sparked by a report of a positive test from trainee John Salder Flagstaff, but researchers are still learning how to find and regulate the drugs in horses. Although two drugs, sold under the brand names Osphos and Tildren, were approved by the Food and Drug Administration for use in horses several years ago, research into the effect of the drugs in young horses and their longevity within the equine body is still holding. (FDA testing focuses on the safety and efficacy of a new drug, not necessarily the state’s race commission’s ability to detect it in a post-race sample from a young racehorse.)
Dr. Heather Knech, renowned equine pharmacologist at the University of California-Davis, gave an overview of current research on bisphosphonates at the most recent virtual conference of the American Association of Equine Practitioners (AAEP).
- Bisphosphonates may be new to the equine world, having been FDA approved for the management of marine syndrome in older horses, but the class of drugs has already been in use in various settings for a few centuries. Knych explained that the substance was first used in the detergent industry in the 19th century as a water softener, anti-corrosion or anti-scaling agent. Their action on calcium carbonate made them effective in these conditions. They were adapted as therapeutic drugs for human bone diseases in the 1970s.
- Although we have often heard of bisphosphonates in humans as part of the treatment of osteoporosis, they have also been used in metastatic bone disorders and multiple myeloma.
- We know that after taking medication, bisphosphonates disappear from the blood fairly quickly – their half-life is 1-2 hours in plasma, but they can remain on bone surfaces for months or years.
- Bisphosphonates appear to prefer stability in trabecular bones–bones such as skulls and ribs that require less mechanical stress–over cortical bones, such as long bones in the limbs. It pulls out of the bone based on the amount of rotation in that bone, which can vary depending on age, exercise and trauma.
- Concentrations of bisphosphonates continue to increase as concentrations decrease elsewhere. It can also be released from the bone into the blood in small amounts and transported to other bony surfaces, although we don’t know much about why and when this happens.
- Knych presented the results of a two-part study led by researchers across multiple universities to learn more about how long bisphosphonates remain in the skeleton. The first part of the project required the administration of two FDA-approved bisphosphonates — Osphos and Tildren — to a total of four horses in undergraduate research programs who had already been identified for euthanasia for unrelated reasons. Bone samples were taken after euthanasia, which came either four days or 30 days after administration in each drug group. Samples from radial bones showed detectable amounts of both drugs after four days of administration, with Tildren levels rising in both samples. Thirty days after taking the drug, both drugs can be found in all the bones taken from them, even the right and left molars. Concentrations of both drugs were higher in tubers (hips).
- In the second phase of the study, researchers tested blood and fluid samples from four horses euthanized for on-track injuries in California — three of whom said they had never received bisphosphonates before, and one who underwent treatment 18 months ago. The team was unable to find any evidence of bisphosphonates in the three horses without a treatment history. A horse treated before 18 months had no detectable amounts of the drug in its serum, urine or synovial fluid, but had a detectable level in a sample of the radial bone.
- These findings, in line with what veterinarians have expected based on human data, indicate that the drug remains on bone surfaces for extended periods of time, and survives on different bones in different ways.
- Knych acknowledged that both parts of the study came from very small sample sizes, as is often the case in academic research with horses, and that more study is needed to better understand how bisphosphonates work in the horses’ body.
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