Clodronate decreases lameness without affecting systemic bone remodeling

Hi, I'm Ashlee Watts. I'm an associate professor of equine orthopedics at Texas A&M University.

In 2014, the bisphosphonates, Tildren (tiludronate) and OSPHOS (clodronate), were approved by the FDA to be used in horses in the United States. When we started using the drug in horses with navicular syndrome, we were seeing that horses were just kind of doing better than we expected, and that improvement was very long-lasting.

One thing that concerned me about a bisphosphonate drug is that in people on long term bisphosphonates use, there is an increased risk of what we call atypical femoral fracture. In women that develop these atypical femoral fractures, we know that they have marked and lasting reductions in their CTX-1 for many months and years.

So we wanted to look at the effect of bisphosphonates in the athletic horses that really replicated the population that we're using bisphosphonates in the most, and that population is middle-aged to slightly older horses that have a few lameness problems. To be enrolled in the study they had to have a previous diagnosis of navicular disease.

During the first eight weeks of the study we just collected blood to measure CTX-1 and develop a baseline for that horse. Then, the horses were given either the study drug, clodronate, or placebo, and we measured lameness and how that change over time as well as CTX-1 for the following eight weeks. In the study we found that CTX-1 in fact did not change after a single dose of clodronate at the label dose.

When I tell equine veterinarians about this result, most of the time their initial reaction is they don't like it, they're a little shocked, they've been telling their clients and their colleagues that they've been modulating bone remodeling in the horse by administering this drug and this is why they're seeing these very profound treatment effects.

To answer the question, so then what's happening - it's still possible that bone remodeling is the effect we're having. It's very possible that in areas of increase bone change or bone disease that there's very high levels of delivery of clodronate. If that's true we could get very important and measurable changes in bone remodeling in these regions without seeing any change in the systemic levels of CTX-1.

I was actually pretty happy with the findings. It means that we can use this drug that we know is very effective at keeping horses with navicular syndrome in work and able to perform with and for their owners without the risk that we see in people of atypical fracture.