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 narrowing. 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 × 15 mg/kg) within D12-D28 (p < 0.01). In contrast, Meloxicam had no effect on radiographic joint lesion and significantly reduced paw volume only within D0-D12 (p < 0.01). Irrespective of dose and administration schedule, TA had a significant partial anti hyperalgesic effect (p < 0.05) within D0-D12 that was sustained until D28. In contrast, Meloxicam had a significant early anti hyperalgesic effect (p < 0.001) that was not sustained overtime. In conclusion, early TA administration showed a beneficial effect on joint lesion severity, with a partial anti hyperalgesic effect indicating that TA might be helpful for the management of arthritic pathologies with bone remodelling and osteolysis.
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