Dose and Administration Schedule Effect of Tiludronate on Joint Damage in the Model of Complete Freund Adjuvant Induced Monoarthritis in Rats.docVIP

Open Journal of Rheumatology and Autoimmune Diseases, 2013, 3, 18-25 /10.4236/ojra.2013.31004 Published Online February 2013 (/journal/ojra) Dose and Administration Schedule Effect of Tiludronate on Joint Damage in the Model of Complete Freund Adjuvant Induced Monoarthritis in Rats Thierry Bertaim , Eric Chapuy , Fran?ois Caussade , Denis Ardid 1 2 3 2 1 Ceva Santé Animale, RD, Libourne, France; Laboratoire de Pharmacologie Médicale, Facultés de Médecine et Pharmacie, 2 Clermont-Ferrand, France; ANS Biotech, Facultés de Médecine et Pharmacie, Clermont-Ferrand, France. Email: thierry.bertaim@ 3 Received November 6 , 2012; revised December 10 , 2012; accepted December 20 , 2012 th th th ABSTRACT The effects of dose and administration schedule of Tiludronate (TA) were assessed on joint lesions and hyperalgesia in a rat model of monoarthritis induced by injection of Complete Freund Adjuvant into the tibio tarsal joint of the hindpaw on day 0 (D0). Rats (n = 12/group) received subcutaneous injection of saline at D1, D4, D8 and D12; single dose (15 mg/kg; 60 mg/kg) at D1 or repeated doses (15 mg/kg) at D1, D4, D8 and D12 of TA; or daily injection of Meloxicam (1 mg/kg, from D1 to D12). Joint lesion severity, hindpaw volume and hyperalgesia were evaluated using radiography, plethysmometry and paw pressure, respectively. TA dose dependently reduced radiographic joint lesion (p 0.001), including bone demineralisation and erosion, joint deformation and to a lesser extent, soft tissue and space articular nar- rowing. These results were supported by a significant limited increase of paw volume at the highest dose, independently of the administration schedule (60 mg/kg, 4