Pharmacological effects of tiludronate in horses after long-term immobilization

Introduction: Tiludronate, a bisphosphonate, has recently been introduced in veterinary medicine to treat orthopedic conditions in the horse. This study was designed to evaluate its effects on biochemical biomarkers of bone metabolism and on bone density and structure in an experimental model of disuse osteoporosis induced by cast application in horses. Methods: Two groups of eight horses were immobilized during 8 weeks. The first group (P-group) received a placebo, and the second group (T-group) received tiludronate 1 mg/kg by slow IV infusion. Both treatments were administered twice, 28 days apart. Immobilization consisted of stall rest with the left forelimb packed in a fiberglass cast. It was followed by a 4-week remobilization period and an 8-week standardized training protocol. One biomarker of bone resorption, the C-telopeptides of type 1 collagen cross-links (CTX-1) and one biomarker of bone formation, the bone isoenzyme of alkaline phosphatase (bone ALP), were assessed. Metacarpus III (MCIII) bone mineral density (BMD) and speed of sound (SOS) were evaluated respectively by dual energy X-ray absorptiometry (DEXA) and quantitative ultrasonography (QUS). Lameness was regularly assessed during the remobilization and training periods. Group- and time-related effects were tested by analysis of variance on repeated measurements. Results: A rapid, transient and significant decrease in CTX-1 concentration was seen after each treatment in the T-group only. No significant differences between groups were seen in the evolution of bone ALP activity. At the end of the experiment, the loss of MCIII BMD measured by DEXA in the immobilized limb was significantly less in the T-group than in the P-group. The MCIII SOS measured by QUS did not significantly vary within or between groups throughout the study. Discussion and conclusions: Tiludronate was found to significantly reduce bone resorption during immobilization, as well as to prevent long-term osteopenia in the immobilized limb. Disuse osteopenia did not affect the lateral superficial cortex of MCIII. (C) 2007 Elsevier Inc. All rights reserved.