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Bisphosphonate Use In Young Horses The Focus Of Texas A&M Study

Texas A&M researchers have created a study to evaluate off-label bisphosphonate use in horses. Originally meant to mitigate navicular pain in mature horses, off-label use of the drug in younger horses may promote bone degradation.

Though the number of equine fatalities from horse racing is decreasing, California, Kentucky, and New York have seen increased racing fatalities in 2018. Lead researcher Dr. Jessica Leatherwood says that a primary concern regarding these breakdowns is the off-label use of bisphosphonates; the study will assist in determining the effects of the drug on developing skeletons.

There is currently no scientific data exploring the effects of bisphosphonate use on young, exercising horses. The study, “Bisphosphonate Pharmacokinetics and Comprehensive Effects on Juvenile Cartilage, Bone Growth and Healing: Implications for Animal Welfare,” received a $500,000 grant from the U.S. Department of Agriculture's National Institute of Food and Agriculture. The particular bisphosphonate that will be studied is clodronate disodium, which is easy to administer and popular.

Racing commissions acknowledge the off-label use of bisphosphonates, but laboratories are unable to reliably test for the drug, limiting the ability to regulate off-label use.

Radiographs are often a key to racehorse sales, particularly in young horses where they expose skeletal health. Off-label use of bisphosphonates may mask potential flaws and cause microdamage accumulation, which could lead to breakdowns. The concern over bisphosphonate use isn't limited to racing; some sport horse disciplines are also limiting or restricting their use.

Horse and sheep models will be used in the study. As sheep are typically processed before they are two years old, they will offer insight into the potential changes in bone and biomechanical properties. The team hypothesizes that younger animals will clear the bisphosphonates more rapidly than older animals, that the drug alters bone in young, exercising horses, and that it will also have anti-inflammatory effects on the joint.

The findings could help shape new regulatory policies on bisphosphonate use in young horses.

Maybe She’s Born With It: Navicular Fractures May Not Be Trauma-Based

Scientists in Belgium and the Netherlands have discovered that abnormalities in the navicular bone that cause lameness may not be related to trauma — some may be genetic. Partitioned navicular bones are often confused with fractures and assumed related to wear or injury.

Drs. Ellen van der Zaag, Erik Weerts, Antoon van den Belt and Willem Back documented three cases of navicular bone partitions whose sections are defined by defects in the bone, covered in smooth cartilage and vary from full separation to shallow indentations. Each was discovered when the lame horse had X-rays taken.

These abnormalities aren't injuries, the researchers note: they are present at birth and could be seen if X-rays were taken before the horse became lame. The researchers believe that these areas are caused by a disturbance in blood vessel arrangement as the bone transforms from cartilage to bone. The partitioning typically develops in two specific areas: one-third of the width of the bone from either end, where blood vessels converge.

The partitions in the bone weaken it. As a horse grows and enters work, these partitions may develop cysts as damaged areas begin to die, making the horse lame. If the condition is found before the horse becomes lame, then corrective trims and shoeing, restricted exercise, and nonsteroidal anti-inflammatory use may help preserve the horse's soundness.

However, the prognosis for soundness is poor even when these tactics are employed. A neurectomy, where the nerve is surgically severed, isn't recommended as it would accelerate cyst formation and increase fracture risk.

University Of Florida Vets Use Placenta-Derived Treatment For Animals With Severe Bone Loss

A human placenta-derived compound developed by a University of Florida faculty member in the Herbert Wertheim College of Engineering is being used with promising results by veterinarians at UF's College of Veterinary Medicine to treat animals with severe bone loss.

Without the compound, the animals — which included a giraffe at the Jacksonville Zoo and Gardens and two pet dogs — would have almost certainly faced amputation of the affected areas, the veterinarians said.

The product's developer, Peter McFetridge, Ph.D., the Integra Lifesciences Term Professor in the J. Crayton Pruitt Family Department of Biomedical Engineering, studies the engineering of viable “living” tissues and organs for the repair and regeneration of diseased tissues. Stan Kim, BVSc., an associate professor of small-animal surgery at UF, learned of McFetridge's work and was intrigued about the placental compound he had been testing in rodent models with some success.

McFetridge and Kim began discussing possibilities for the product's additional use in small animals. Kim treated the dogs with the new compound at UF's Small Animal Hospital earlier this year.

“Both dogs had very bad fractures that did not heal and had lost a lot of bone,” Kim said. “Typical treatments usually fail in these types of cases.”

The dogs were completely healed after the placental treatment, he said, and are doing very well.

“The most exciting thing about the placental compound is that it seems to regenerate bone in a remarkable manner,” Kim said. “Although our main excitement is with regenerating bone, we have also had very positive results with wounds.”

Meanwhile, Kim's colleague, Adam Biedrzycki, BVSc., Ph.D., an assistant professor of equine surgery at UF, had been contacted in January by the Jacksonville Zoo and Gardens about the possibility of helping with the treatment of a 2-year-old reticulated giraffe named JoJo, who had become severely lame in October. Despite various treatments provided at the zoo, JoJo's foot problems had worsened.

“They asked if I or a colleague had any interest in consulting or participating in the case,” Biedrzycki said.

JoJo had a severe case of septic arthritis in the medial claw of her right front foot, he said. The zoo had been treating the giraffe with analgesics, antibiotics and stall rest, and had even applied a custom-made boot from a farrier who works with exotic hoof stock. However, radiographs appeared to show bone abnormalities and deterioration, contributing to lesions and fluid drainage.

“I told them that giraffes are certainly not my area of expertise, but in a bovine or horse with this condition we would do massive bone grafts, place antibiotic beads, administer antibiotics directly into the limb and spend lots of time and money trying to save the digit. In a cow, we would drill out and remove the dead or damaged tissue surrounding the foot bone. Then we would cast it followed by regular bandage changes on the limb and leave it to heal.”

That was essentially what was done with the giraffe, he said — but with the addition of the placental compound.

Biedrzycki spoke with Kim, who had used the placental compound successfully in a few cases. Kim put Biedrzycki in touch with McFetridge to further discuss the product and its potential for treating infections and stimulating bone growth.

Biedrzycki then brainstormed with Jacksonville Zoo veterinarian Yousef Jafarey, D.V.M., and his team to develop a plan: They would cut out the diseased bone, clean out the area and put in bone allografts, antibiotic beads and the placental product “to try to speed things up.”

The giraffe wore a cast on her foot, and three cast changes were performed six weeks apart. The second time, the area was cleaned out a bit more and additional placental compound was applied, Biedrzycki said.

“It was a very big deal,” he said. “I was really impressed with the whole team effort.”

That effort involved the zoo's keepers, its animal health team, an anesthesia crew and many more people performing various duties along the way, Biedrzycki said.

“You also had an army of people massaging the giraffe's neck, another team putting antibiotics in the vein, and the surgery team working on the foot, along with a farrier to help trim the foot,” he said. “There were probably about 30 people altogether working on this giraffe. I think they have the whole procedure down to an art now.”

He said the collaborative effort and range of expertise at the zoo was likely why JoJo did so well with the procedure and continues to improve.

“So far, the outcome is excellent,” he said. “The infection is gone and there is new bone growth at the site showing fusion between the bones, which is really unheard of. She still has some limb swelling, which will take a while to go down. But JoJo seems pretty happy at this stage.”

Jafarey said the zoo was astounded at JoJo's progress since working with Biedrzycki and the UF team.

“The introduction of this new compound has been integral in her recovery and we are excited that our organization participated in this groundbreaking research,” he said.

The material the UF veterinarians have been using started out being used to drive the regeneration of large vessels for heart bypass, McFetridge said.

“I never thought it could be used clinically, as it contains a lot of human maternal tissues, from the placenta, as well as the fetal side of the placenta,” he said. “But after several animal studies, we discovered that there was no negative immune response at all, and that it had a potent healing effect across a range of different tissues.”

Unlike typical biologic treatments that have one response, the placenta-derived material seems to promote healing in several vastly different tissues including bone, blood vessels and skin, McFetridge added.

McFetridge and two of his biomedical engineering department colleagues, Jon Dobson, Ph.D., the J. Crayton Pruitt Family Professor, and Blanka Sharma, Ph.D., an associate professor and the J. Crayton Pruitt Family Term Fellow, have co-founded a company in Gainesville, 42Bio, to commercialize the product for veterinary applications. They recently got private funding to move forward with research facilities at The Hub, UF's business incubator.

“So we're hoping to be able to provide this amazing material more widely, especially as we find out, almost daily, how well it helps heal critical injuries. The healing responses we've seen in the giraffe and the dogs are almost jaw-dropping.”