Acute phase response and mineral status following low dose intravenous zoledronic acid in children

Bone. 2007 Sep;41(3):366-70. doi: 10.1016/j.bone.2007.05.002. Epub 2007 May 13.


Introduction: Previous reports have shown a high frequency of hypocalcaemia and flu-like symptoms following an initial first zoledronic acid dose of 0.02-0.025 mg/kg in children.

Methods: We systematically evaluated the mineral status and symptomatology of 63 children with a variety of bone disorders treated with an initial zoledronic acid dose of 0.0125 mg/kg. The Mann-Whitney U test, chi-squared test and Fisher's exact test were used as appropriate.

Results: 0.0125 mg/kg zoledronic acid reduced the incidence and intensity of hypocalcaemia but not the incidence of the flu-like symptoms compared to higher doses. Within the low dose cohort, flu-like symptoms were associated with an acute inflammatory response. Children who became hypocalcaemic received a higher dose in relation to their body mass index and body surface area.

Conclusion: Reducing the initial zoledronic acid dose in children decreased the incidence of hypocalcaemia and thus improved safety. Dosing on the basis of body mass index or body surface area instead of body weight may further reduce the incidence of hypocalcaemia.

Publication types

  • Clinical Trial

MeSH terms

  • Acute-Phase Reaction / chemically induced*
  • Adolescent
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Density Conservation Agents / adverse effects*
  • Bone Diseases / drug therapy*
  • C-Reactive Protein / analysis
  • C-Reactive Protein / drug effects
  • Calcium / blood
  • Child
  • Child, Preschool
  • Diphosphonates / administration & dosage*
  • Diphosphonates / adverse effects*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypocalcemia / chemically induced
  • Hypocalcemia / epidemiology
  • Imidazoles / administration & dosage*
  • Imidazoles / adverse effects*
  • Infusions, Intravenous
  • Male
  • Parathyroid Hormone / blood
  • Phosphates / blood
  • Zoledronic Acid


  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Parathyroid Hormone
  • Phosphates
  • Zoledronic Acid
  • C-Reactive Protein
  • Calcium