Supplemental Material for: Short-term side effects of first bisphosphonate infusion in children with different underlying bone pathologies

Acute-phase reactions within days after the first infusion, andsymptom scores at 6–8 weeks were obtained by structured telephone interviews and analysed using multivariable models adjusted for age, sex, and diagnostic subgroup.</p><p dir="ltr">Results</p><p dir="ltr">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 lowestin 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.</p><p dir="ltr">Conclusion</p><p dir="ltr">This prospective, multicentre study demonstrates clinically relevant variability in both acute-phase reactions and treatment response following bisphosphonate treatment initiation in a large cohort ofchildren 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.</p>