Safety of intravenous neridronate in pediatric patients: insights from the monocentric retrospective NAPOLEON cohort

Background: Evidence on the safety of intravenous neridronate (IV NER) in children with conditions other than osteogenesis imperfecta (OI) remains limited. This retrospective study describes adverse events, including acute phase reactions (APR) and hypocalcemia, over a median follow-up of 20 months in a monocentric pediatric cohort with rheumatological conditions. Methods: Thirty-seven children with OI and other bone diseases undergoing infusion of IV NER were included. Clinical, demographic, and serologic data were recorded. Results: The most common side effect was APR (62%), which occurred less frequently in patients on chronic oral cholecalciferol supplementation: 43% of the 14 patients who did not experience APR were supplemented, while none of the 23 subjects who developed APR received supplementation (p = 0.001). Conversely, pre-infusion 25-dihydroxycholecalciferol and calcium levels did not differ between patients who experienced APR and patients without APR (24.23 ± 12.96 vs 27.56 ± 11.81 ng/mL, respectively; p = 0.496). Premedication with prednisone does not seem to be effective in the prevention of APR. Hypocalcemia was rare and asymptomatic in all cases. Conclusion: NER appears safe across different pediatric conditions, with predictable first-infusion reactions. The role of vitamin D and premedication in children candidate to NER infusion should be further confirmed in larger cohorts.