Ask Your Veterinarian Presented By Kentucky Performance Products: Dr. Larry Bramlage On Bisphosphonates In Young Horses – Where Are We Now? by Paulick Report Staff|11.21.2022|11:30am Dr. Larry Bramlage Veterinarians at Rood and Riddle Equine Hospital answer your questions about sales and healthcare of Thoroughbred auction yearlings, weanlings, 2-year-olds and breeding stock. Question: You first raised the alarm about the potential drawbacks of bisphosphonate use in young racehorses several years ago now. Where are we with these drugs now? Dr. Larry Bramlage, Rood and Riddle Equine Hospital: In 2016, we began talking to our clients about a phenomenon that we were seeing more and more frequently in young racehorses. The problem was being seen in all common bone injuries that we encounter in the racehorse from dorsal cortical stress fractures to condylar fractures to the very common subchondral bone inflammation/bruising of the distal cannon bones. In some horses, orthopedic injuries were not healing or healing very slowly compared to what we expected. Clinical experience, retrospective studies of success rates, and published papers has given us pretty solid evidence of what to expect as the healing time with the treatment of the commonly encountered racehorse conditions. But suddenly some horses were taking three or four times the time expected to heal and a few never fully healed. The number of these slow healing injuries continued to grow during 2015. As we began assessing the histories of horses where the aberrant healing was occurring, many had a history of bisphosphonate use as yearlings to improve the radiographs for sale or as a racehorse during a bout of lameness. So, we began discussing the findings and informing veterinarians, trainers, and owners of the possible detrimental side effect of bisphosphonate use. Veterinarians in many locations were making the same observations of disturbed healing and possible increased injury rates in young training horses of several breeds. Bisphosphonates were approved in 2014. In 2015 we began to see storms of slow healing fractures and slow healing distal cannon bone subchondral bone inflammation/bruising. That led to the suspicion that bisphosphonates may be the reason. Bone healing is a two-phase process. The bone bridges the fracture gap with new, poorly-organized bone that can be formed very quickly. Then it remodels the stabilized fracture back to the bone's pre-fracture architecture. Once the fracture gap is filled, the bone damaged by the fracture and the newly-deposited bone are removed and replaced with the appropriate trabecular or cortical bone, depending on the structure involved. This process involves two cell types — osteoclasts which remove bone and osteoblasts which make bone. As the osteoclasts remove the weak bone, the osteoblasts follow immediately behind to reconstruct the normal bone. The anatomy varies depending on which bone is injured and where it is injured, but bone is one of the few tissues capable of perfectly replacing itself when injured. Bisphosphonates kill osteoclasts. It bonds to the surface of bone and when the osteoclasts try to remove the bone that needs to be replaced, they die after ingesting the bisphosphonate. This arrests the remodeling process and stalls bone healing by stopping the remodeling phase of healing. This is true for macro injuries such as fractures and for micro injuries which result from routine training. The injured bone can make new bone but it can't be remodeled without osteoclasts to clear the way for the osteoblasts. Osphos, one of two bisphosphonates FDA-approved for use in horses four years old and up So what good are bisphosphonates and why were they developed? Bisphosphonates were developed to arrest the hormone-driven bone remodeling which is common in post-menopausal women who get too little exercise. The hormonal driven remodeling removes an inappropriately large amount of bone and weakens the skeleton, especially the vertebrae, which when weakened can result in the “dowager's hump” spinal deformity. The bisphosphonates were given to prevent the removal of the bone by killing the osteoclasts. But bisphosphonates also have another effect. They cause non-specific pain relief, analgesia, in bone. This led to their use to manage pain in bone tumors in people, especially in cancer of the spine. The mechanism is still unclear, but the analgesia is significant and non-specific so if you give it systemically it will help manage the pain no matter where the tumor is located. This analgesia led to the use of bisphosphonates to manage lameness in horses. The proposed mechanism is that it stops excessive bone remodeling in sites of lameness by arresting bone removal. Whether blocking bone re-absorption or a primary analgesia is the mechanism of action is still debated. The blocking of bone re-absorption led to use to try and increase the density in the skeleton by stopping bone loss to the remodeling process. So, bisphosphonates gained popularity to try to increase the density of bone in bone remodeling sites such as sesamoids and navicular bones. And, they became popular as the perfect lameness treatment; it is effective if the lameness originates in the bone, and you don't even have to know the site of origin. But there is a price to be paid. Killing the osteoclasts prevented the normal bone remodeling necessary to maintain a developing skeleton (e.g., the young training racehorse). This retards adaptation to training, potentially increasing the susceptibility to injury, and it nearly arrests the remodeling process that is the second phase of bone healing in a fracture or in trauma to the bone. The difficulty is if a horse is given bisphosphonates it binds to the interior surfaces of bone and can persist two years or more. So many horsemen weren't even aware, when a horse arrived for training, that there was a history of bisphosphonate use. Support our journalismIf you appreciate our work, you can support us by subscribing to our Patreon stream. Learn more.Subscribe To their credit, most horsemen and veterinarians quickly understood the risks of bisphosphonate use and the use rapidly declined over the next two years in young training horses. The drug still has a place in certain conditions in older horses, but it does not in the young training athlete. It can be dangerous to the horse's career and their resistance to injury. It is approved by the FDA for horses with navicular disease who are four years old or older. So, where are we now? Sales companies and racing jurisdictions have stepped in and outlawed the use of bisphosphonates in most venues. Currently we still see an occasional horse with a fracture that shows disturbed healing but there is nowhere near the incidence of the problem that was occurring in 2015 and 2016. Veterinarians, owners, farm managers and trainers appear to have mitigated the use of bisphosphonates and should be credited with their response to protect the health and welfare of the horses. Sales companies and regulatory agencies have done their part and the current situation appears to be generally free from bisphosphonate use in the young growing and training horses. A horse that we suspect is showing signs of bisphosphonate treatment in the past still presents occasionally, but not regularly any longer. I suspect bisphosphonates are still intermittently used when a horse does not respond to common treatments. To all of our credit, this has been a positive response to an initially unknown complication of treatment that was detrimental to the racehorse. For all of the things we wring our hands about that we have trouble changing, this is one we could, and did, circumvent for our good and for the good of our athletes. Dr. Larry Bramlage of Rood & Riddle Larry Bramlage is a 1975 graduate of the Kansas State University College of Veterinary Medicine (DVM) and received a Master of Science degree from Ohio State (MS) in 1978. He holds a Diploma of the American College of Veterinary Surgery (Diplomate ACVS). Bramlage is an internationally recognized equine orthopedic surgeon, and is a senior surgeon at Rood and Riddle Equine Hospital in Lexington, Kentucky. He is a past President of the American Association of Equine Practitioners, and of the American College of Veterinary Surgeons. In recognition of his dedication and contribution to Thoroughbred racing, Bramlage was awarded the 1994 Jockey Club Gold Medal for contributions to Thoroughbred Racing in the United States. He is also a past chairman of the Research Advisory Committee of the Grayson-Jockey Club Research Foundation and serves on the Board of Directors for that organization. His additional honors include the 1997 Tierlink Hochmoor Prize for his work regarding the internal fixation of fractures, the 1998 distinguished alumnus award from The Ohio State University, Alumni Fellow Award from Kansas State University, a British Equine Veterinary Association's Special Award of Merit, and the American College of Veterinary Surgeons Legends award for the development of the fetlock arthrodesis procedure for horses in 2009, and the Thoroughbred Club Testimonial Award in 2014. He has received the American Association of Equine Practitioners Distinguished Service Award twice. He was elected to membership in the Jockey Club in 2002 and to Distinguished Lifetime Membership in the American Association of Equine Practitioners in 2010.