Short-term side effects of first bisphosphonate infusion in children with different underlying bone pathologies.

BACKGROUND: Intravenous bisphosphonates are the primary pharmacological intervention for both primary and secondary paediatric osteoporosis. Following the successful use of bisphosphonates in children with osteogenesis imperfecta (OI), indications have expanded to a broad range of bone pathologies with variable underlying pathophysiology. While bisphosphonate use appears to be safe in children, data on risk factors for acute-phase reaction remain sparse. A prospective characterisation of adverse effects - including baseline musculoskeletal symptoms - has not previously been performed in children. METHODS: In this prospective, multicentre observational study, children and adolescents initiating intravenous bisphosphonate therapy at 10 tertiary centres were enrolled. Baseline assessments included diagnosis, fracture history, and patient/proxy-reported pain, fatigue, mobility, and well-being. Acute-phase reactions within days after the first infusion, and symptom scores at 6-8 weeks were obtained by structured telephone interviews and analysed using multivariable models adjusted for age, sex, and diagnostic subgroup. RESULTS: A total of 139 children and adolescents (mean age 9.8 years, 37% female) were included across a spectrum of primary and secondary bone disorders, of whom 83% had a history of fractures. Acute-phase reaction rates varied substantially between diagnostic subgroups: febrile episodes were most frequent in children with inflammatory conditions (71.4%) and OI type III/IV (59.1%) but lowest in OI type I (29.2%), with a comparable pattern for nausea (57.1% vs 22.7% vs 20.8%). Across the cohort, all four symptom domains improved significantly at 6-8 weeks after treatment (p<0.05), with the greatest improvements in patients with inflammatory conditions and those with the highest baseline burden. In zoledronate‑treated children, nausea showed a clear dose relationship and did not occur below 0.02 mg/kg. CONCLUSIONS: This prospective, multicentre study demonstrates clinically relevant variability in both acute-phase reactions and treatment response following bisphosphonate treatment initiation in a large cohort of children with bone conditions. Recognition of subgroup‑dependent risk and benefits, and the dose‑dependent occurrence of nausea with zoledronate, supports dose-adapted initiation protocols, particularly for high‑risk groups such as children with inflammatory bone conditions.