Safety margin of clodronate use in horses

My name is Chris Kawcak. I'm an equine surgeon, boarded in sports medicine, practicing surgeon in sports medicine, and clinician at Colorado State University.

Our research group was basically asked to participate in a safety study for OSPHOS (clodronate). Whenever you approve a drug, you need to prove both efficacy and safety. And the safety studies are done to look at a wide spectrum of dosing just to make sure that we understand it's safe at recommended doses, but also what is that kind of safety boundary above the recommended dose.

Basically it was a six month study in which a group of horses was followed over that period of time. There were a number of parameters that were evaluated, we just happened to do the density, and Dr. [Sue] Stover's lab had done the mechanical strength part of the study.

Those horses were brought into the study, evaluated at Day 0, and treated monthly during that time with one of four doses – either untreated, and then at the recommended dose, and then at two and three times the recommended dose. And that gives you the safety margin you feel comfortable working at. And FDA does look at that, they want to know just how safe it really is.

So the horses were treated monthly; we had x-rays obtained prior to treatment and the at the end of the study. We looked at two time points on density just to see if there was a change due to the influence of treatment during that time. And there was not at any of the treatment doses.

When you look at the data – when I look at it from a clinician's standpoint – what I look at is that it was not only proven safe at that dose, but it has a very wide safety margin. That, to me, as a clinician means that I can feel very comfortable that I'm not going to influence the integrity of the horse's musculoskeletal system – or at least the bone – negatively, by using this at the recommended dose.

For me, it's not just the safety at the dose that's recommended, it's the safety margin at the higher doses that make me feel very comfortable about using it. And that's what people want to know, right? When you make a recommendation for a treatment: A. They want to know, "Is it going to work?" and B, "How safe is it?" So when you can translate those data to the clients, it definitely helps them relax about how safe that medication is.