Zoledronic acid in pediatric metabolic bone disorders

Abstract

Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its convenience of shorter infusion time and less frequent dosing compared to pamidronate. Many studies have also demonstrated beneficial effects of ZA in other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD), chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review summarizes pharmacologic properties, mechanism of action, dosing regimen, and therapeutic outcomes of ZA in a variety of metabolic bone disorders in children. Several potential novel uses of ZA are also discussed. Safety concerns and adverse effects are also highlighted.

Keywords: Zoledronic acid (ZA); acute phase reaction (APR); bone mineral density (BMD); fragility fractures; hypercalcemia; metabolic bone disease; osteonecrosis (ON); osteoporosis.

Figure 1

Chemical structures of BP and ZA. (A) General structure of BP. Side chain R1 and R2 can be modified to alter the hydroxyapatite binding capability and the potency of BP; (B) structure of ZA with an imidazole-ring side chain containing 2 critically positioned nitrogen atoms. BP, bisphosphonate; ZA, zoledronic acid.