Tiludronate infusion in the treatment of bone spavin: A double blind placebo‐controlled trial

Gough, M. R.; Thibaud, Dominique; Smith, Roger K.

doi:10.1111/j.2042-3306.2010.00120.x

Cited by 54 publications

(41 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This effect may be useful to treat conditions associated with an increase in bone turnover, such as navicular disease or osteoarthritis. In fact, some horses with navicular disease (Denoix, Thibaud & Riccio, 2003), osteoarthritis of the distal tarsal joints (Gough, Thibaud & Smith, 2010) or the thoracolumbar facet joints (Coudry et al, 2007) exhibited decreased signs of pain associated with their condition after systemic tiludronate treatment. In humans, atypical subtrochanteric and femoral shaft fractures have been reported after years of treatment (Nieves & Cosman, 2010).…”

Section: Introductionmentioning

confidence: 99%

Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses—a preliminary investigation

Duesterdieck-Zellmer

Moneta

Ott

et al. 2014

PeerJ

View full text Add to dashboard Cite

To determine effects of intraarticularly administered tiludronate on articular cartilage in vivo, eight healthy horses were injected once with tiludronate (low dose tiludronate [LDT] 0.017 mg, n = 4; high dose tiludronate [HDT] 50 mg, n = 4) into one middle carpal joint and with saline into the contralateral joint. Arthrocentesis of both middle carpal joints was performed pre-treatment, and 10 min, 24 h, 48 h, 7 and 14 days after treatment. Synovial nucleated cell counts and total solids, tiludronate, sulfated glycosaminoglycan (sGAG), chondroitin sulfate 846 epitope (CS-846, a measure of aggrecan synthesis), and collagen type II cleavage neoepitope (C2C) concentrations were determined. Histologic analysis of joint tissues and sGAG quantitation in cartilage was performed at 14 days in HDT horses. Data were analyzed by repeated measures non-parametric ANOVA and Wilcoxon signed-rank test. High dose tiludronate administration produced synovial fluid tiludronate concentrations of 2,677,500 ng/mL, exceeding concentrations that were safe for cartilage in vitro, and LDT administration produced synovial fluid concentrations of 1,353 ng/mL, remaining below concentrations considered potentially detrimental to cartilage. With HDT, synovial fluid total solids concentration was higher at 24 h and 7 days and sGAG concentration was higher at 48 h, compared to control joints. Synovial fluid CS-846 concentration was increased over pre-treatment values in HDT control but not in HDT treated joints at 24 and 48 h. All joints (HDT and LDT control and treated) showed a temporary decrease in synovial fluid C2C concentration, compared to pre-treatment values. Histologic features of articular cartilage and synovial membrane did not differ between HDT treated and control joints. High dose tiludronate treatment caused a transient increase in synovial total solids and temporarily increased proteoglycan degradation in cartilage. Although clinical significance of these changes are questionable, as they did not result in articular cartilage damage, further investigation of the safety of intraarticular HDT in a larger number of horses is warranted.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses—a preliminary investigation

Duesterdieck-Zellmer

Moneta

Ott

et al. 2014

PeerJ

View full text Add to dashboard Cite

show abstract

“…The anion of tiludronic acid (tiludronate, TLN) is a non-nitrogen-containing BP that acts on bone through mechanisms that involve induction of osteoclast apoptosis and prevention of extracellular degradation and of pro-inflammatory cytotrafficking [10], leading to decreased mineralized matrix resorption. This drug is recommended for skeletal disorders characterized by an increased and abnormal bone remodelling, such as Paget's disease, and is currently the only BP approved in veterinary medicine to alleviate clinical signs of an OA condition in horses [11]. There is yet insufficient data to claim a potentially beneficial effect of TLN on the pathological changes encountered in OA.…”

Section: Introductionmentioning

confidence: 99%

Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model

et al. 2011

View full text Add to dashboard Cite

IntroductionThe aim of this prospective, randomized, controlled, double-blind study was to evaluate the effects of tiludronate (TLN), a bisphosphonate, on structural, biochemical and molecular changes and function in an experimental dog model of osteoarthritis (OA).MethodsBaseline values were established the week preceding surgical transection of the right cranial/anterior cruciate ligament, with eight dogs serving as OA placebo controls and eight others receiving four TLN injections (2 mg/kg subcutaneously) at two-week intervals starting the day of surgery for eight weeks. At baseline, Week 4 and Week 8, the functional outcome was evaluated using kinetic gait analysis, telemetered locomotor actimetry and video-automated behaviour capture. Pain impairment was assessed using a composite numerical rating scale (NRS), a visual analog scale, and electrodermal activity (EDA). At necropsy (Week 8), macroscopic and histomorphological analyses of synovium, cartilage and subchondral bone of the femoral condyles and tibial plateaus were assessed. Immunohistochemistry of cartilage (matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS5)) and subchondral bone (cathepsin K) was performed. Synovial fluid was analyzed for inflammatory (PGE2 and nitrite/nitrate levels) biomarkers. Statistical analyses (mixed and generalized linear models) were performed with an α-threshold of 0.05.ResultsA better functional outcome was observed in TLN dogs than OA placebo controls. Hence, TLN dogs had lower gait disability (P = 0.04 at Week 8) and NRS score (P = 0.03, group effect), and demonstrated behaviours of painless condition with the video-capture (P < 0.04). Dogs treated with TLN demonstrated a trend toward improved actimetry and less pain according to EDA. Macroscopically, both groups had similar level of morphometric lesions, TLN-treated dogs having less joint effusion (P = 0.01), reduced synovial fluid levels of PGE2 (P = 0.02), nitrites/nitrates (P = 0.01), lower synovitis score (P < 0.01) and a greater subchondral bone surface (P < 0.01). Immunohistochemical staining revealed lower levels in TLN-treated dogs of MMP-13 (P = 0.02), ADAMTS5 (P = 0.02) in cartilage and cathepsin K (P = 0.02) in subchondral bone.ConclusionTiludronate treatment demonstrated a positive effect on gait disability and joint symptoms. This is likely related to the positive influence of the treatment at improving some OA structural changes and reducing the synthesis of catabolic and inflammatory mediators.

show abstract

“…Tiludronic acid is licensed for treatment of inflammatory and degenerative joint disease in horses at a dose of 1 mg/kg by intravenous infusion over 30 minutes. Improvement of lameness in horses suffering from bone spavin (Gough and others 2010) and navicular disease (Denoix and others 2003) has been demonstrated in horses treated with tiludronic acid.…”

Section: Bisphosphonatesmentioning

confidence: 99%

Managing orthopaedic pain in horses

Bardell¹

2017

In Practice

View full text Add to dashboard Cite

show abstract

Tiludronate infusion in the treatment of bone spavin: A double blind placebo‐controlled trial

Abstract: Tiludronate in combination with controlled exercise offers an alternate medical treatment for bone spavin.

Cited by 54 publications

References 33 publications

Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses—a preliminary investigation

Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses—a preliminary investigation

Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model

Managing orthopaedic pain in horses

Contact Info

Product

Resources

About