A Review of the Efficacy of Tiludronate in the Horse

Kamm, Lacy; McIlwraith, Wayne; Kawcak, Chris E.

doi:10.1016/j.jevs.2008.02.007

Cited by 35 publications

(21 citation statements)

References 23 publications

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“…Navicular disease cannot be readily cured, and treatment has focused on supportive therapies including rest, corrective shoeing, and anti-inflammatory medications (Schoonover et al 2005, Belknap 2010). However, the association with bone loss has suggested that anti-resorptive agents such as bisphosphonates may be of benefit for the treatment of the osseus component of the disease (Denoix et al 2003, Kamm et al 2008. Bisphosphonates, as shown in experimental animal and human studies, act at several key places to inhibit osteoclast recruitment, adhesion, differentiation and resorptive activity; and to induce osteoclast apoptosis (Fleisch 2000, Russell 2007).…”

Section: Introductionmentioning

confidence: 99%

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Clodronate disodium for treatment of clinical signs of navicular disease – a double-blinded placebo-controlled clinical trial

Frevel¹,

King²,

Kolb³

et al. 2017

PHK

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Summary: Navicular disease (also referred to as palmar foot syndrome or navicular syndrome, although not completely the same) causes lameness in many horses of all activity groups.The objective of this study was to compare clodronate efficacy at improving lameness grade in horses with clinical signs of navicular disease to that of horses given placebo. A randomized, multi-center, double-blinded clinical field study was conducted on 146 horses with forelimb lameness due to navicular disease. Navicular disease was confirmed by lameness examination (with diagnostic nerve blocks) and radiography of the affected distal forelimb(s). At study initiation, treated horses received 1.4 mg/kg clodronate disodium IM, and control (placebo) horses received a corresponding IM volume of 0.9 % saline. Primary effectiveness was evaluated at Day 56 using a lameness grading scale, with positive response defined as improvement by at least 1 grade in the limb with the most apparent lameness, with no worsening of the lameness grade (compared to baseline) in the contralateral forelimb. Positive response rates at Days 28 and 180 were also recorded. On Day 56, 75 % of horses in the clodronate group were considered showing a positive response, versus only 3 % in the placebo group (p = 0.003). Of the 86 horses treated with clodronate, 8 horses had an improvement of 3 lameness grades, 45 horses improved by 2 lameness grades and 16 horses improved by one lameness grade. The clodronate positive response rate remained high through Day 180 (65 %). Adverse events (primarily abdominal pain) were generally few, mild, and transient. In this study, clodronate disodium was demonstrated to be safe and effective in reducing the clinical signs of lameness associated with navicular syndrome.

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Section: Introductionmentioning

confidence: 99%

“…This class of drugs has also been evaluated as therapy for a variety of equine orthopedic problems, and the non-nitrogenous bisphosphonate tiludronate has been approved in several countries for treatment of navicular syndrome or bone spavin (Kamm et al 2008). …”

Section: Introductionmentioning

confidence: 99%

Clodronate disodium for treatment of clinical signs of navicular disease – a double-blinded placebo-controlled clinical trial

Frevel¹,

King²,

Kolb³

et al. 2017

PHK

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“…There are several reports on using antiresorptive drugs in equine bone resorption disorders (Coudry et al, 2007;Katzman et al, 2012). Moreover, some antiresorptives have been proposed for the treatment of dorsal metacarpal disease (bucked shins) and other bone resorption disorders in horses (Delguste et al, 2007;Kamm et al, 2008;Hussein & Bertone, 2015).…”

Section: Introductionmentioning

confidence: 99%

Repeated oral administration of a cathepsin K inhibitor significantly suppresses bone resorption in exercising horses with evidence of increased bone formation and maintained bone turnover

Hussein

Dulin

Smanik

et al. 2016

Vet Pharm & Therapeutics

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Our investigations evaluated the effect of VEL-0230, a highly specific irreversible inhibitor of cathepsin K (CatK). The objectives of our study were to determine whether repeated dosing of a CatK inhibitor (CatKI) produced a desired inhibition of the bone resorption biomarker (CTX-1), and document the effect of repeated dosing on bone homeostasis, structure, and dynamics of bone resorption and formation in horses. Twelve young exercising horses were randomized in a prospective, controlled clinical trial and received 4 weekly doses of a CatKI or vehicle. Baseline and poststudy nuclear scintigraphy, blood sampling and analysis of plasma bone biomarkers (CTX-1 and osteocalcin), poststudy bone fluorescent labeling, and bone biopsy were performed. Bone specimens were further processed for microcomputed tomography and bone histomorphometry. Each dose of this CatKI transiently inhibited plasma CTX-1 (reflecting inhibition of bone collagen resorption) and increased bone plasma osteocalcin concentrations, with no detectable adverse effect on normal bone turnover in the face of exercise. Bone morphology, density, and formation rate were not different between control and treated group. Further investigation of CatK inhibition in abnormal bone turnover is required in animals with bone diseases.

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“…5 Zoledronate is used in humans for the treatment of Paget' s disease of bone 8 as well as for osteoporosis in postmenopausal women. 7 Although there have been several recent studies investigating the clinical efficacy of tiludronate for the treatment of a variety of orthopedic conditions in horses, 14 we elected to use zoledronate in the study reported here because of its increased potency and duration of action as compared with tiludronate in humans 5 and because of its use for the treatment of conditions that appear to have similarities to this BFD in humans. 7,8 To the authors' knowledge, the use of zoledronate in horses has not been previously described.…”

Section: Discussionmentioning

confidence: 99%