Early in 2014, the U.S. Food and Drug Administration approved tiludronate for intravenous administration in horses with navicular disease. Despite being a relatively new drug used in veterinary medicine, some equine practitioners are already prescribing tiludronate for “off-label” use in horses with other conditions, such as osteoarthritis by injecting the drug directly into the joint rather than using a systemic route of administration.

“Potential side effects associated with tiludronate and the high costs of treatment after intravenous injection are likely the reasons veterinarians are trying to use lower doses by administering the drug directly into joints rather than systemically,” explains Katja Duesterdieck-Zellmer, DrMedVet., MS, PhD, Dipl. ACVS, assistant professor in the Oregon State University College of Veterinary Medicine Department of Clinical Sciences, in Corvallis.

The articular cartilage lining the ends of the bones inside joints, however, is delicate, and direct contact between high concentrations of tiludronate and cartilage could be detrimental. Laboratory studies support this hypothesis: In one study equine cartilage cells treated with high concentrations of tiludronate underwent increased programmed cell death and had an increased rate of release of glycosaminoglycans, both of which indicate cartilage damage. In that same study, though, low concentrations of tiludronate were beneficial to cartilage.

To better characterize tiludronate's impact on articular cartilage in horses, Duesterdieck-Zellmer and colleagues injected a low-dose (0.017 mg) or high-dose (50 mg) of tiludronate or saline (for a control) in