Cyclical iv therapy with pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study we evaluated the effect of this therapy on bone and mineral metabolism in 165 patients with OI types I, III, and IV (age, 2 wk to 17.9 yr; 86 girls and 79 boys). All patients received iv pamidronate infusions on 3 successive days, administered at age-dependent intervals of 2-4 months. During the 3 d of the first infusion cycle, serum concentrations of ionized calcium dropped by 0.14 +/- 0.008 mmol (mean +/- SE; P < 0.001), and serum PTH levels transiently almost doubled (P < 0.001). At the same time, urinary excretion of the bone resorption marker type I collagen N-telopeptide related to creatinine (uNTX/uCr) decreased by 61-73% (P < 0.001). Two to 4 months later, ionized calcium had returned to pretreatment levels, and uNTX/uCr remained 30-35% lower than at baseline (P < 0.001). During 4 yr of pamidronate therapy (n = 40 patients), ionized calcium levels remained stable, but PTH levels increased by about 30% (P < 0.01). uNTX/uCr, expressed as a percentage of the age- and sex-specific mean value in healthy children, decreased from 132 +/- 13% (mean +/- SE) at baseline to 49 +/- 3% after 4 yr of therapy (P < 0.001). In conclusion, serum calcium levels can decrease considerably during and after pamidronate infusions, requiring close monitoring especially at the first infusion cycle. In long-term therapy, bone turnover is suppressed to levels lower than those in healthy children. The consequences of chronically low bone turnover in children with OI are unknown at present.