Bisphosphonates are a class of drugs which includes both tildronate and clodronate. They were approved by the U.S. Food and Drug Administration in 2014 for controlling clinical signs associated with navicular syndrome in horses four years of age and older.
Since that time, some veterinarians have used these products off-label to treat other equine bone issues including osteoarthritis, bucked shins, sesamoiditis and subchondral bone cysts. Bisphosphonates are thought to provide significant analgesic effects and may even help improve radiographic images of conditions such as sesamoiditis. The provision of pain relief can be beneficial in appropriate situations, but we also need to consider the fine line between relieving pain and masking pain. Furthermore, we need to account for the additional risks associated with bisphosphonates.
With our current level of knowledge and understanding of the actions of bisphosphonates, we should seriously question their use. Normally in horses, bone turns over continually (remodels). This is due to the activity of specialised cells called osteoclasts and osteoblasts. Osteoclasts break down (resorb) old bone while osteoblasts create new bone. This ensures bones remain strong and healthy and allows them to adapt to changes in exercise level or mechanical stress placed upon them. This adaptation and strengthening is an important mechanism in protecting against stress-induced bone injuries. Increased bone fragility has been seen in animals given high doses or long-term doses of bisphosphonates, a likely result of the inability to repair micro-damage within bone.
Bisphosphonates inhibit osteoclasts, thereby blocking excess bone resorption. But they’ve also been shown to be anti-angiogenic (preventing new blood vessel growth). New blood vessel growth is an essential component to repair the normal micro-damage that naturally occurs during training, competition and racing. It is important to remember that this normal repair and recovery of this micro-damage actually make bones stronger. Furthermore, curbing the action of osteoclasts interrupts the remodelling process: the activity of osteoblasts and osteoclasts is a finely balanced process. Inhibiting the activity of osteoclasts interferes with the osteoblasts, therefore they don’t kick into gear to build new bone.
It can be easy to skim over the fine print on pharmaceutical labels and pamphlets, yet it is important to note that the FDA clearly outline some of these risks. They declare that bisphosphonates inhibit osteoclast activity and decrease bone turnover, thereby potentially affecting bone growth. Ultimately, this inhibition of bone remodelling can place racehorses and performance horses at greater risk of more frequent and serious injuries.
Whilst the medication is approved for use in controlling clinical signs of navicular disease in horses four years and above, it is important to remember that the action of bisphosphonates is systemic: that is, it affects the whole skeletal system, not just the navicular. We also need to remember that in many horses, some bones (particularly of the spinal column) aren’t fully developed until ages five to six or older.
Athletic performance aside, the safe use of bisphosphonates has not been evaluated in breeding horses or pregnant mares. Studies in laboratory animals have demonstrated bisphosphonates to cause abnormal foetal development, likely due to drug-induced alterations in maternal and foetal bone uptake. To compound this issue further, bisphosphonates have a very long half-life (meaning they can stay in the horse’s system many years after cessation of treatment). As a consequence, they can affect the health of both mare and foal long after the use of the medication has stopped.
When considering the risks of bisphosphonates in lactating mares and nursing foals, we need to be aware that metabolites of these pharmaceuticals may be excreted in milk and absorbed by nursing animals. This has the potential to negatively impact the bone development of the offspring. Again, given the extremely long half-life of bisphosphonates, these effects may still occur years after bisphosphonates were last used in the mare. The use of the vast majority of pharmaceuticals comes with side effects which we need to consider in the context of a horse’s long-term health, performance and potentially reproductive life. Before rushing to ‘treat’ a health, injury or performance issue, we should first address why the health or injury concern has occurred. This requires honestly and critically reviewing training, feeding/nutrition, recovery, medication use and management practices. If a horse has excessive inflammation and/or soreness in an area, it is a sign that things aren’t right. Without identifying and addressing the underlying cause of bone inflammation and injury the problem persists. To try and rectify the problem with the non-discriminate use of drugs with known serious side effects is risky at best. Whilst providing pain relief can be beneficial in appropriate situations, masking pain and accelerating bone damage and loss is not.
Camilla Whishaw is a highly regarded, experienced horsewoman and naturopath, helping to holistically treat and manage a broad range of equine health conditions and injuries, with a passion for mare and stallion fertility.
As a world-renowned practitioner, presenter, author, and consultant in the field of Equine Naturopathy, Camilla shares her knowledge through keynote presentations, interviews, lectures, panel sessions, and workshop training.