“I wish we'd never seen these drugs,” said renowned orthopedic surgeon Dr. Larry Bramlage at the conclusion of a recent presentation about bisphosphonates.
Four years after the Food and Drug Administration approved the use of Tildren and Osphos (both trade names for bisphosphonates) for use in adult horses suffering from navicular syndrome, Bramlage said he's seeing unintended side effects from people using the drug off label.
As Bramlage explained at a recent client education seminar held by Rood and Riddle Equine Hospital, there are three main types of cells associated with bone repair and growth: osteoblasts, which make new bone; osteoclasts, which break down damaged or inferior bone, and osteocytes, which direct the repair.
When a horse has a fracture, the crack is initially filled by the osteoblasts with a temporary boney substance called woven bone, which can be made very quickly but is not very strong. Over time, osteoclasts clear away woven bone, which is poorly organized and weak, allowing osteoblasts to lay down the better organized and stronger lamellar bone. The lamellar bone fills in the crack and makes the bone whole again, both practically and on radiograph.
Bones are constantly breaking down and building back up in response to normal wear and tear and training.
Bisphosphonates work by poisoning osteoclasts and for this reason are used to slow osteoporosis in people. They also have an analgesic effect, which is why they are used in human bone tumor patients. This is also why they are presented as an option for horses dealing with painful and hard-to-pinpoint inflammation due to navicular syndrome.
Bramlage is finding bisphosphonates' mechanism of action also disrupts the natural healing process in young horses during training.
“I thought initially it might create a lot of acute fractures,” he said. “I don't think it increases their incidence very much. Where it causes a problem is whenever you're trying to heal something that's happened as a result of training and needs to repair. Part of the horse's natural coping mechanism is disabled.”
Bramlage is seeing stunted healing on radiographs of horses who have had surgery or rest to repair fractures which normally would have improved in a couple of months. Sometimes as much as 14 months after injury, the x-rays still show the injuries that have been “patched up” with woven bone still persist with original fractures visible.
“I've spent 40 years looking at horses' bones trying to understand the process of damage and repair that we consistently deal with in the racehorse. In the last two years we've had horses' injuries that don't behave anything like they did in my first 40 years,” he said. “We can no longer depend on the repair process that we have come to expect as normal for the horse. Bisphosphonates also ‘mute' the normal bone turnover we depend on in bone scans.”
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