What we know regarding the use of bisphosphonates in horses
Authors: Mitchell Colin , McNulty Margaret 
Published: June 2021

Currently two bisphosphonates (BPs) are licensed for use in horses. Both tiludronate (TIL) and clodronate (CLO) are labelled specifically for the treatment of navicular disease, but are administered frequently for other suspected causes of lameness. Recommended administration routes are not always used, resulting in the risk of potential toxicities or increased patient morbidity. Numerous reports exist describing subjective improvements in subjective lameness following the administration of TIL or CLO, but little objective data exists to confirm this, or even reveal the effects these drugs have on the equine athlete. Our group has investigated the influence of TIL and CLO on pelvic biopsies from horses, before and 60 days after drug administration. MicroCT and histomorphometry were performed on all samples to evaluate changes to bone cells and structure, following a single dose of TIL (1mg/kg) or CLO (1.8mg/kg). Sixty days was chosen as the second biopsy date based on the clinical improvement observed in lameness studies reported in the literature. Biopsies were collected from a total of 19 horses (5 each for either TIL or CLO and 9 controls) at day 0 (pretreatment) and subsequently at day 60. No biologically significant histomorphometric or microCT differences were revealed in the bone structure, cells, or remodeling kinetics between the treated or control horses or between Day 0 biopsies (internal controls). This may have been related to study design and sampling times, or may reflect the relatively low potency of TIL and CLO as inhibitors of osteoclastic activity in the horse. The CLO group and their control horses also had the original biopsy site biopsied again at day 60, to investigate the effect on bone healing. Again, no changes were observed between the treated and untreated horses. TIL has been shown to have negative effects on chondrocytes, in horses, when administered at higher levels than those achieved following IV administration. This was investigated in response to veterinarians giving TIL via intraarticular injection or intravenous regional limb perfusions. The effects of high levels of CLO on chondrocytes have not been investigated to date, but the authors have completed a pharmacokinetic study which revealed plasma, synovial and urinary levels of CLO subsequent to administration of a single dose of CLO, at the appropriate dose. Renal injury is an acknowledged potential complication in healthy horses following administration of BPs. In the horses we investigated after administration of CLO, no alterations in serum BUN or creatinine or urine protein:creatinine ratios were observed. This information will help direct future studies into the safety and viability of CLO and its use in horses. With the lack of response seen in normal equine bone using clinically relevant doses, future investigations need to focus on examining the responses in a diseased state, or in a more refined model. Unfortunately, navicular disease is characterized by a wide variety of bone pathology and clinical signs, resulting in no standard model for investigation. For this reason, future investigation is necessary to identify the effects and potential benefits of these commonly used medications.Support or Funding InformationFunded by the LSU SVM EHSPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.