Treatment of Paget's disease of the bone: long-term effect of neridronate in a real-life setting.

Abstract

Bisphosphonates represent the gold standard treatment for Paget's disease of bone. Neridronate is a potent bisphosphonate, licensed in Italy for this use, but only few clinical trials have investigated the outcomes of this treatment. The aim of our study was to report our long-term experience with intravenous Neridronate. This is a 48 months observational, descriptive and prospective study on patients with active Paget's disease of bone treated with intravenous Neridronate. Patients underwent laboratory tests (total alkaline phosphatase (ALP), calcium, phosphate, 25 OH Hydroxivitamin D, serum protein electrophoresis, parathyroid hormone) at the time of diagnosis and every 6 months. In all subjects, mutations in the SQSTM1 and ZNF687 genes were searched. The primary endpoint was the treatment efficacy in term of rate of therapeutic response at 48 months (normalization of ALP levels or a reduction of at least 75% in total ALP excess). Fifteen patients (10 female, mean age 70.3 years) were enrolled at our division from 2016 to 2020. One was positive for the ZNF687 gene mutation. After 48-month follow-up, the therapeutic response was maintained in 80% of patients treated with intravenous neridronate. ALP values were higher at 48 months than at 6 months, but this difference was not clinically relevant because the percentage of subjects who maintained a therapeutic response at 48 months was not significantly different from that observed at 6 months (80% vs. 86.6%, P=0.62). One patient had a biochemical relapse, and was retreated with the same therapeutic regimen, achieving a good response. Treatment with intravenous neridronate is effective in inducing and maintaining sustained remission in patients with PDB for at least 48 months. Administration in single intravenous infusion may improve long-term compliance compared to oral formulations.