Pharmacological effects of tiludronate in horses after long-term immobilization.
Abstract: 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 I 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. 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.
Publication Date: 2007-05-23 PubMed ID: 17604709DOI: 10.1016/j.bone.2007.05.005Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study examined the effects of tiludronate, a drug used in veterinary medicine for bone disorders, on horses that were immobilized for a lengthy period. The researchers focused on how the drug impacted bone health, specifically looking at changes in bone metabolism markers and bone structure and density. The results showed that tiludronate significantly reduced bone loss during immobilization.
Research Methodology
- The study involved two groups, each containing eight horses. All horses were immobilized for an 8-week period by putting the left forelimbs of each horse in a fiberglass cast.
- The first group, referred to as the P-group, received a placebo treatment, while the second group, referred to as the T-group, received tiludronate at a dose of 1 mg/kg through slow intravenous infusion.
- There were two rounds of treatment administered to the horses, which were carried out 28 days apart.
- After immobilization, the horses underwent a 4-week remobilization period and an 8-week standardized training protocol.
- The researchers evaluated one biomarker of bone resorption – C-telopeptides of type I collagen cross-links (CTX-1), and one biomarker of bone formation – the bone isoenzyme of alkaline phosphatase (bone ALP).
- Bone mineral density (BMD) of the third metacarpus bone (MCIII) and speed of sound (SOS) were assessed using dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasonography (QUS), respectively.
Results and Observations
- Only the T-group showed a rapid, transient, and significant decrease in CTX-1 concentrations after each treatment – an indicator of reduced bone resorption.
- There were no notable differences between the groups in terms of changes in bone ALP activity, a marker for bone formation.
- At the end of the experiment, DEXA measurements showed that the loss of Bone Mineral Density (BMD) in the immobilized limb of horses from the T-group was significantly less than that of the P-group, suggesting that tiludronate limited bone loss during immobilization.
- The speed of sound (SOS) measurements of MCIII obtained through QUS – an indicator of bone quality – showed no significant changes within or between groups.
Conclusions
- The results demonstrated that tiludronate significantly reduced bone resorption during the immobilization period and prevented long-term bone loss in the immobilized limb.
- The researchers concluded that Disuse Osteopenia – a condition where
bone loss occurs due to less usage or inactivity – did not affect the lateral superficial cortex of MCIII.
Cite This Article
APA
Delguste C, Amory H, Doucet M, Piccot-Crézollet C, Thibaud D, Garnero P, Detilleux J, Lepage OM.
(2007).
Pharmacological effects of tiludronate in horses after long-term immobilization.
Bone, 41(3), 414-421.
https://doi.org/10.1016/j.bone.2007.05.005 Publication
Researcher Affiliations
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liege, Belgium. cdelguste@ulg.ac.be
MeSH Terms
- Absorptiometry, Photon
- Alkaline Phosphatase / blood
- Alkaline Phosphatase / drug effects
- Animals
- Bone Density / drug effects
- Bone Density Conservation Agents / pharmacology
- Bone Diseases, Metabolic / prevention & control
- Bone Remodeling / drug effects
- Bone and Bones / drug effects
- Collagen Type I / blood
- Collagen Type I / drug effects
- Diphosphonates / pharmacology
- Horses
- Male
- Peptides / blood
- Peptides / drug effects
- Restraint, Physical
Citations
This article has been cited 10 times.- Vergara-Hernandez FB, Nielsen BD, Colbath AC. Is the Use of Bisphosphonates Putting Horses at Risk? An Osteoclast Perspective. Animals (Basel) 2022 Jul 3;12(13).
- Santosuosso E, Leguillette R, Vinardell T, Filho S, Massie S, McCrae P, Johnson S, Rolian C, David F. Kinematic Analysis During Straight Line Free Swimming in Horses: Part 1 - Forelimbs. Front Vet Sci 2021;8:752375.
- Mitchell A, Watts AE, Ebetino FH, Suva LJ. Bisphosphonate use in the horse: what is good and what is not?. BMC Vet Res 2019 Jun 24;15(1):211.
- Delguste C, Doucet M, Gabriel A, Guyonnet J, Lepage OM, Amory H. Assessment of a bone biopsy technique for measuring tiludronate in horses: a preliminary study. Can J Vet Res 2011 Apr;75(2):128-33.
- Micheau L, Audigié F, Moiroud C, Jacquet S. New Model of Disuse-Induced Bone Density Loss in Horses. Animals (Basel) 2025 Oct 29;15(21).
- Gaulmin P, Marin F, Moiroud C, Beaumont A, Jacquet S, De Azevedo E, Martin P, Audigié F, Chateau H, Giraudet C. Description and Analysis of Horse Swimming Strategies in a U-Shaped Pool. Animals (Basel) 2025 Jan 13;15(2).
- Tippen SP, Metzger CE, Sacks SA, Allen MR, Mitchell CF, McNulty MA. Clinically relevant doses of tiludronate do not affect bone remodelling in pasture-exercised horses. Equine Vet J 2025 Mar;57(2):513-521.
- Reis IL, Lopes B, Sousa P, Sousa AC, Caseiro AR, Mendonça CM, Santos JM, Atayde LM, Alvites RD, Maurício AC. Equine Musculoskeletal Pathologies: Clinical Approaches and Therapeutical Perspectives-A Review. Vet Sci 2024 Apr 26;11(5).
- Ayodele BA, Pagel CN, Mackie EJ, Armour F, Yamada S, Zahra P, Courtman N, Whitton RC, Hitchens PL. Differences in bone turnover markers and injury risks between local and international horses: A Victorian Spring Racing Carnival study. Equine Vet J 2025 Mar;57(2):333-346.
- Wilcox CV, Knych HK, Katzman SA, Arthur RM, Rodriguez V, Finno CJ. Effect of clodronate on gene expression in the peripheral blood of horses. J Vet Pharmacol Ther 2024 May;47(3):187-192.
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