Evaluation of the efficacy and safety of oral tiludronate in paget's disease of bone

Abstract

Objective. To assess the optimal dosage of oral tiludronate in Paget's disease of bone. Methods. We studied 149 patients with Paget's disease, in a double‐blind, randomized, placebo‐controlled trial. Patients were randomly assigned to 1 of 5 therapeutic groups: a daily dose of 100 mg, 200 mg, 400 mg, or 800 mg of oral tiludronate, or a placebo. Treatment was for 3 months, followed by 3 months of placebo‐controlled followup. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatinine (OH/Cr) were measured monthly, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self‐evaluated from a visual analog scale and a global pain index. Results. Statistical analysis revealed that beginning at a dosage of 200 mg/day, there was a direct dose‐dependent effect on the reduction of SAP and OH/Cr levels. Reduction of SAP levels was clinically significant at a dosage of 400 mg (44.9 ± 4.2% reduction at 90 days and 49.2 ± 4.5% at 180 days, mean ± SEM) and at 800 mg (53.4 ± 5% at 90 days and 59.3 ± 4.6% at 180 days). There was a significant reduction in pain in all groups, including the group taking placebo. In only those taking 800 mg/day of tiludronate was there a significant frequency of complete resolution of pain (versus placebo). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance of all 5 regimens was good. Exhaustive biochemical investigations failed to reveal significant toxicity of tiludronate up to the 800‐mg daily dose investigated. Conclusion. Because of its significantly better antiresorptive effects and greater analgesic properties (compared with lower dosages), combined with the excellent clinical and biochemical tolerance, the 800‐mg daily dose of tiludronate appears to be optimal for the treatment of Paget's disease of bone.

Comparative prospective, double‐blind, multicenter study of the efficacy of tiludronate and etidronate in the treatment of paget's disease of bone

“…The tolerability of tiludronate is comparable to that of etidronate, except that there is an earlier occurrence of gastrointestinal disturbances with tiludronate. This is consistent with the findings of previous studies of tiludronate and shows that, although the drug is well-tolerated in general, its use is associated with gastrointestinal disturbance in a certain proportion of patients (14). Although this is usually mild, requiring no treatment, it is the most frequent reason for early termination of treatment.…”

“…One of them, tiludronate (chloro-4phenyl thiomethylene bisphosphonate), is able to reduce bone turnover without mineralization impairment 852 ROUX ET AL or other major side effects (12,13). The efficacy and safety of oral tiludronate iin Paget's disease of bone have been reported (14). A residual activity of tiludronate after cessation of its administration has been reported in Paget's disease: (14).…”

“…The efficacy and safety of oral tiludronate iin Paget's disease of bone have been reported (14). A residual activity of tiludronate after cessation of its administration has been reported in Paget's disease: (14). This is related to its retention in bone, a common feature of bisphosphonates (15).…”

Paget Disease of Bone

“…1 Several studies have established that antipagetic therapy for bone pain may result in clinical benefit. 8,9 Biomechanical therapy (eg, heel lifts, canes, and crutches) may help ambulation.…”

Paget's Disease of Bone (Osteitis Deformans)

“…Tiludronate, a bisphosphonate recently approved by the FDA, was administered to 128 patients with Paget's disease in an oral dose of 200 mg bid for 6 months. After 3 and 6 months, serum alkaline phosphatase decreased by 47% and 58%, respectively 67–69 . Tiludronate was also administered in doses of 200 to 400 mg/day for 24 weeks to 139 patients in a placebo‐controlled study.…”