The Horse

MAR 2019

The Horse:Your Guide To Equine Health Care provides monthly equine health care information to horse owners, breeders, veterinarians, barn/farm managers, trainer/riding instructors, and others involved in the hands-on care of the horse.

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A24 March 2019 The Horse | AAEP Wrap-Up that population may be inappropriate." McLellan described a paper on five racehorses with bucked shins that re- sponded to treatment with a combination of weekly regional limb perfusions (isolat- ed delivery of the drug to the lower limb via a vein) with tiludronate, shock wave therapy, rest, and controlled exercise. However, he said, "it is impossible to ascertain the influence of tiludronate on healing due to the presence of multiple concurrently used modalities." In summary, he said, there's a limited number of equine-specific research stud- ies into bisphosphonate use, and even fewer racehorse-specific investigations. McLellan said vets have anecdotally used bisphosphonates to treat: ■ Stress remodeling—McLellan said some practitioners believe that "if bone resorption is halted, the bone will not become weakened and, therefore, stress fractures will not occur." But he re- minded attendees that microdamage in bone is a natural part of bone remodel- ing. "So, bisphosphonate administra- tion to inhibit bone resorption could, in fact, reduce the entire healing process, leading to weaker bones and increasing the risk of stress fractures," he said. ■ Sesamoiditis—Affected horses have inflammation between the sesamoid bones and the suspensory ligament branch. McLellan said this inflammato- ry cycle can lead to sesamoid bone lysis (bone loss) and pain. Proponents of this use say bisphosphonates could decrease lysis in these horses, he said. "The risk in the racehorse is that it's not known whether the anecdotally reported abate- ment of clinical signs is due to analgesic effects of the bisphosphonates or a true resolution of the disease process." ■ Osteoarthritis—Studies conducted in nonracehorses have shown that bisphosphonates might help relieve clinical signs of lower hock OA, McLel- lan said. But currently, IA bisphospho- nate use in horses should be considered experimental, McLellan said. (Tiludro- nate is labeled to be given intravenous- ly and clodronate intramuscularly.) ■ Subchondral bone cysts— Bisphosphonates could benefit horses with cystlike lesions (fluid- and scar- tissue-filled cavities) in bone directly beneath the articular cartilage, said McLellan, thanks to their anti-inflam- matory and antiresorptive properties. However, there's currently no support- ive evidence. ■ Palmar/plantar osteochondral disease (POD)—Researchers believe this de- generative condition affecting the lower ends of the cannon bones develops due to subchondral bone injury associated with a bone's failure to adapt to train- ing. "There's limited evidence to support the use of bisphosphonates in POD, and a recent Havemeyer meeting report rec- ommended that bisphosphonates have no place in the treatment of this disease based on current evidence," he said. Next, McLellan shared potential risks of off-label bisphosphonate use. Analgesic effects Pain relief can be beneficial in appropriate situations. But in racehorses it can also be detrimental, and inappropriate analgesia is one of the major sources of concern regarding bisphosphonates within the racing indus- try. "It's hard to differentiate from clinical signs alone how much improvement is caused by actual healing and how much is due to pain relief," McLellan said. The juvenile skeleton Young bones remodel constantly to adapt to training. Anything inhibiting this could ultimately weaken the skeleton. So, these drugs are only labeled for use in horses over 4. Drug testing Testing for bisphospho- nates presents another dilemma. They have a short detection window in urine and serum and, while they remain in bone significantly longer, it's difficult to extract bone for analysis in the living horse, said McLellan. And, there's limited research on withdrawal times in horses. In summary, said McLellan, while bisphosphonates might be useful for treating some diseases, they could have detrimental effects when used inappropri- ately. "Based on the existing knowledge," he said, "off-label bisphosphonate use in racehorses could be putting both the patient and the practitioner at risk." h Tildren ® (tiludronate disodium) BISPHOSPHONATE DRUG FOR INTRAVENOUS INFUSION. For use in horses only WARNINGS Do not use in horses intended for human consumption. NSAIDs should not be used concurrently with Tildren ® . Concurrent use of NSAIDs with Tildren ® may increase the risk of renal toxicity and acute renal failure. HUMAN WARNINGS Not for human use. Keep this and all drugs out of the reach of children. Consult a physician in case of accidental human exposure. CAUTION Federal law restricts this drug to use by or on the order of a licensed veterinarian. INDICATION Tildren ® is indicated for the control of clinical signs associated with navicular syndrome in horses. CONTRAINDICATIONS Do not use in horses with known hypersensitivity to tiludronate disodium or to mannitol. Do not use in horses with impaired renal function or with a history of renal disease. Bisphosphonates are excreted by the kidney; therefore, conditions causing renal impairment may increase plasma bisphosphonate concentrations resulting in an increased risk for adverse reactions. PRECAUTIONS Approximately 30-45% of horses administered Tildren ® will demonstrate transient signs consistent with abdominal pain (colic). Horses should be observed closely for 4 hours post-infusion for the development of clinical signs consistent with colic or other adverse reactions. Colic signs can last approximately 90 minutes and may be intermittent in nature. Hand walking the horse may improve or resolve the colic signs in many cases. If a horse requires medical therapy, non-NSAID treatments should be administered due to the risk for renal toxicity. Avoid NSAID use. Horses should be well hydrated prior to administration of Tildren ® due to the potential nephrotoxic effects of Tildren ® . Tildren ® should be used with caution in horses receiving concurrent administration of other drugs that may reduce serum calcium (such as tetracyclines) or whose toxicity may exacerbate a reduction in serum calcium (such as aminoglycosides). Horses with HYPP (heterozygous or homozygous) may be at an increased risk for adverse reactions, including colic signs, hyperkalemic episodes, and death. The safe use of Tildren ® has not been evaluated in horses less than 4 years of age. Bisphosphonates should not be used in pregnant or lactating mares, or mares intended for breeding. Bisphosphonates have been shown to cause fetal developmental abnormalities in laboratory animals. DOSAGE AND ADMINISTRATION A single dose of Tildren ® should be administered as an intravenous infusion at a dose of 1 mg/kg (0.45 mg/ lb). The infusion should be administered slowly and evenly over 90 minutes to minimize the risk of adverse reactions. Maximum effect may not occur until 2 months post-treatment. For ADMINISTRATION INSTRUCTIONS (preparation of the reconstituted solution (20mg/mL) and preparation of the solution for infusion) and for complete product information, please read the insert contained within the product packaging. STORAGE Sterile powder (not reconstituted): Store at controlled room temperature 68°F-77°F (20°C-25°C). After preparation, the infusion should be administered either within 2 hours of preparation, or it can be stored for up to 24 hours under refrigeration at 36°F-46° F (2°C-8°C) and protected from light. HOW SUPPLIED Tildren ® is supplied in a 30mL glass vial as a white, sterile lyophilized powder containing 500mg tiludronic acid (as tiludronate disodium) packaged in a folding carton. For technical assistance or to report suspected adverse reactions, call 1-888-524-6332. INFORMATION FOR OWNERS Prior to Tildren ® administration, owners should be advised of the potential for adverse reactions in the hours or days following treatment. Adverse reactions within 4 hours post dosing may include signs of colic (manifested as pawing, stretching, getting up and down, sweating, rolling, looking at flanks, kicking at belly, frequent gas, and pacing). Owners should be instructed to contact their veterinarian immediately if any adverse reactions are observed. Owners should be advised to consult with their veterinarian prior to the administration of an NSAID following Tildren ® administration. Made in Canada Patent information: U.S. patent 6,057,306 ONLINE extras Visit ■ Hoof Conformation, Balance, and Hind-Limb Lameness,

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