ABSTRACT
A double-blind, randomized, placebo-controlled study was performed to evaluate the effect of oral tiludronate therapy in 139 patients with active Paget's disease of bone. Patients received placebo (N = 48), tiludronate 200 mg (N = 45), or tiludronate 400 mg (N = 46) once daily for 12 weeks. Biochemical and clinical responses were observed during the 12 week treatment phase and during an additional 12 week observation phase of the study. Both the 200 and 400 mg tiludronate groups experienced significant reduction in serum alkaline phosphatase (SAP) and urinary indices of bone resorption. After 12 weeks of therapy, the SAP levels decreased 46% from baseline values in the 200 mg group and 51% from baseline values in the 400 mg group. At the end of the 24 week study, SAP levels were reduced 47% and 58% from baseline in the 200 and 400 mg groups, respectively. The SAP reduction at 24 weeks was greater in the 400 mg group than the 200 mg group (p < 0.05). At the end of 24 weeks, 51% of patients treated with 200 mg and 72% of those who received 400 mg of tiludronate had experienced a reduction in SAP of greater than 50% (p = 0.043), and 7% and 35% of patients in the 200 and 400 mg groups, respectively, had experienced normalization of SAP (p = 0.001). There was no difference in incidence of side effects in patients taking tiludronate or placebo. In conclusion, oral tiludronate is an effective and well-tolerated therapy for patients with Paget's disease of bone. Daily therapy with 400 mg tiludronate for 12 weeks is more effective than a daily dose of 200 mg for 12 weeks.
