EFFICACY AND TOLERABILITY OF A NEW FORMULATION OF ORAL TILUDRONATE (TABLET) IN THE TREATMENT OF PAGETS-DISEASE OF BONE

We sought to assess efficacy and safety of a new oral formulation (tab let) of tiludronate in Paget's disease of bone. We studied 128 patient s with Paget's disease in an open-label uncontrolled trial. Patients r eceived a daily dose of 400 mg oral tiludronate (two tablets). Treatme nt was for 6 months. Serum alkaline phosphatase activity (SAP) and fas ting urinary excretion of hydroxyproline/creatinine (OH/Cr) were measu red every 3 months, as were biochemical parameters reflecting renal, h epatic, and hematologic functions. Analgesic efficacy was self-evaluat ed from a visual analog scale (VAS). Statistical analysis revealed a s ignificant reduction from baseline in SAP and OH/Cr levels, as well as VAS scores. In the whole population with evaluation under treatment, there was a reduction in initial SAP activity after 3 months (47.2 +/- 2.2%, mean +/- SEM) and 6 months (58.3 +/- 2.3%). In the population w ith SAP levels above twice the upper limit at inclusion and with evalu ation at month 3 and month 6 (n = 96), the reduction in SAP levels was 49.3 +/- 2.4% after 3 months and of 59.5 +/- 2.6% after 6 months (ANO VA time effect, p = 0.0001). Aside from mild gastrointestinal disturba nces, as experienced with other oral bisphosphonates, clinical toleran ce was good. Exhaustive biochemical investigation failed to reveal sig nificant toxicity of tiludronate tablets at the dose of 400 mg/day. Th e dose of 400 mg daily of this new formulation appears to be a satisfa ctory tiludronate regimen for the treatment of Paget's disease of bone .