COMPARATIVE PROSPECTIVE, DOUBLE-BLIND, MULTICENTER STUDY OF THE EFFICACY OF TILUDRONATE AND ETIDRONATE IN THE TREATMENT OF PAGETS-DISEASE OF BONE

Objective, To compare the efficacy and safety of tiludronate and etidr onate at the same dosage (400 mg/day) for the treatment of active Page t's disease of bone, Methods, We studied 234 patients with radiologic lesions characteristic of Paget's disease of bone and serum alkaline p hosphatase (AP) concentrations at least twice the upper limit of norma l, in a prospective, randomized, double-blind, multicenter clinical tr ial lasting 6 months, Patients were randomly allocated into 1 of 3 tre atment groups: tiludronate for 3 months followed by placebo for 3 mont hs, tiludronate for 6 months, or etidronate for 6 months, Serum AP lev els and urinary hydroxyproline excretion were measured at baseline and after 3 months and 6 months, Patients with a reduction of at least 50 % in the serum AP concentration were considered to be responders, Resu lts, After 3 months, the proportion of responders was higher in the ti ludronate group (57.4%) than in the etidronate group (13.9%) (P < 0.00 01), In the etidronate group, this percentage was lower among patients who had received previous treatment with a bisphosphonate (2.3%) than among those who had not (28.6%) (P < 0.01), Previous bisphosphonate t reatment was not associated with response in the tiludronate group, Af ter 6 months, the proportion of responders did not differ between the 2 tiludronate groups (60.3% and 70.1%), but was lower in the etidronat e group (25.3%) (P < 0.0001), There was a higher proportion of patient s with treatment-resistant disease (<25% reduction of serum AP) in the etidronate group (51.9%) than in the tiludronate 3-month group (17.9% ) or the tiludronate B-month group (19.5%) (P < 0.0001). Gastrointesti nal disturbances were more common, and occurred earlier, with tiludron ate, but they were mostly mild, requiring no treatment, Conclusion, Ti ludronate at -400 mg/day for 3 months or 6 months is more effective th an the same dosage of etidronate for 6 months in the treatment of Page t's disease,