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Abstract: Background: Children receiving glucocorticoids (GCs) are at an increased risk of fragility fractures. Conservative measures may be inadequate in treating low bone mass, giving rise to fractures in this population; as such, attention has turned to the use of bisphosphonates. Objective: The goal of this study was to evaluate the bioavailability and single-dose tolerability of alendronate (ALN) in children receiving a stable dose of GCs. Methods: Children (ages 4–17 years) receiving GC treatment for their chronic illnesses received intravenous (125 μg) and oral (35 mg) ALN in a 2-period, randomized crossover study, with doses separated by at least a 7-day washout period. Urine was collected for either 8 or 24 hours after drug administration to determine urinary excretion of ALN and bioavailability. Tolerability was assessed by continuous collection of adverse events reported during the study. The main outcome measures were total urinary excretion rates, oral bioavailability of ALN, and adverse events. Results: There were 12 patients in the 4- to 11-year-old group (mean age, 8.1 years; 5 girls) and 12 patients in the 12- to 17-year-old group (mean age, 14.3 years; 5 girls). The least-squares mean bioavailability (90% CI) for children aged 4 to 11 years (n = 12) was 0.43% (0.27–0.67) and for children aged 12 to 17 years (n = 12) it was 0.39% (0.26–0.60). The least-squares mean bioavailability for all ages combined was 0.41% (0.30–0.56), with no statistical difference between the 2 age groups. The total urinary excretion of ALN after the intravenous dose was similar between groups. Fifteen patients reported a total of 36 transient clinical nonserious adverse events, all of which were mild or moderate in intensity; the most common were headache (n = 13), abdominal pain (n = 3), limb, neck, or facial pain (n = 6), and ankle or knee swelling (n = 3). Conclusions: The mean oral bioavailability of ALN was similar to previous pharmacokinetic studies in children with osteogenesis imperfecta and slightly lower than that observed in historical adult controls. Alendronate was generally well tolerated, with minor adverse events that resolved uneventfully. Elucidation of the full adverse-effect profile of this agent was limited by the single-dose nature of this study, and robust comparisons of the pharmacokinetics of ALN in different age groups may need a larger number of patients. [Copyright &y& Elsevier]