title: Short-Term Safety of Zoledronic Acid in Young Patients With Bone Disorders: An Extensive Institutional Experience.
abstract: BACKGROUND
  Zoledronic acid (ZA) is increasingly used in young patients with bone disorders. However, data related to the safety of ZA administration in this population are limited.
  
  
  OBJECTIVE
  The study aimed to characterize the short-term safety profile of ZA and identify risk factors for ZA-related adverse events (AEs) in young patients.
  
  
  METHODS
  This was a retrospective chart review of inpatients and outpatients less than 21 years old who received at least one ZA infusion between July 2010 and January 2014 at The Children's Hospital of Philadelphia.
  
  
  RESULTS
  Eighty-one patients (56% male; median age, 12 y; age at first infusion, 0.5 to 20 y) with diverse skeletal disorders received a total of 204 infusions. The most common indications were osteoporosis (33% of cohort) and osteogenesis imperfecta (27.2%). The median ZA dose was 0.025 mg/kg (interquartile range, 0.025-0.05); the median dosing interval was 6 months (range, 1 to 25.6 mo). AEs were mild and more common after the first ZA infusion in patients with no previous bisphosphonate exposure: hypophosphatemia (25.2% of infusions), acute phase reactions (19.1%), and hypocalcemia (16.4%). Symptomatic hypocalcemia requiring iv calcium occurred after two infusions. ZA dose was significantly associated with hypophosphatemia, but not other AEs. Hypocalcemia was more common in patients with high bone turnover as assessed by preinfusion alkaline phosphatase levels. AEs were not associated with diagnosis, baseline serum calcium, or calcium/calcitriol supplementation.
  
  
  CONCLUSIONS
  Acute AEs related to ZA infusion in youths are common, occur principally after the first ZA infusion in bisphosphonate-naive patients, and are typically mild and easily managed. Future prospective studies are needed to determine the potential long-term risks, as well as benefits, of ZA therapy in the pediatric population.
authors: Division of General Pediatrics (S.G.), Division of Endocrinology and Diabetes (D.R.W., M.A.L.), Division of Genetics (P.K.), and Department of Pharmacy (K.H., H.M.M.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (P.K., M.A.L.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; and University of Rochester School of Medicine and Dentistry (D.R.W.), Rochester, New York 14642.
authors: Sobenna
authors: S
authors: George
authors: Division of General Pediatrics (S.G.), Division of Endocrinology and Diabetes (D.R.W., M.A.L.), Division of Genetics (P.K.), and Department of Pharmacy (K.H., H.M.M.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (P.K., M.A.L.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; and University of Rochester School of Medicine and Dentistry (D.R.W.), Rochester, New York 14642.
authors: David R
authors: DR
authors: Weber
authors: Division of General Pediatrics (S.G.), Division of Endocrinology and Diabetes (D.R.W., M.A.L.), Division of Genetics (P.K.), and Department of Pharmacy (K.H., H.M.M.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (P.K., M.A.L.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; and University of Rochester School of Medicine and Dentistry (D.R.W.), Rochester, New York 14642.
authors: Paige
authors: P
authors: Kaplan
authors: Division of General Pediatrics (S.G.), Division of Endocrinology and Diabetes (D.R.W., M.A.L.), Division of Genetics (P.K.), and Department of Pharmacy (K.H., H.M.M.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (P.K., M.A.L.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; and University of Rochester School of Medicine and Dentistry (D.R.W.), Rochester, New York 14642.
authors: Kelly
authors: K
authors: Hummel
authors: Division of General Pediatrics (S.G.), Division of Endocrinology and Diabetes (D.R.W., M.A.L.), Division of Genetics (P.K.), and Department of Pharmacy (K.H., H.M.M.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (P.K., M.A.L.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; and University of Rochester School of Medicine and Dentistry (D.R.W.), Rochester, New York 14642.
authors: Heather M
authors: HM
authors: Monk
authors: Division of General Pediatrics (S.G.), Division of Endocrinology and Diabetes (D.R.W., M.A.L.), Division of Genetics (P.K.), and Department of Pharmacy (K.H., H.M.M.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Pediatrics (P.K., M.A.L.), University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; and University of Rochester School of Medicine and Dentistry (D.R.W.), Rochester, New York 14642.
authors: Michael A
authors: MA
authors: Levine
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced; D000293:Adolescent; D000469:Alkaline Phosphatase / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001847:Bone Diseases / Q000150:complications* / Q000188:drug therapy; D002117:Calcitriol / Q000627:therapeutic use; D002118:Calcium / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy; D006996:Hypocalcemia / Q000188:drug therapy; D017674:Hypophosphatemia / Q000097:blood / Q000139:chemically induced; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007223:Infant; D008297:Male; D010013:Osteogenesis Imperfecta / Q000188:drug therapy; D010024:Osteoporosis / Q000188:drug therapy; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D002117:Calcitriol; D002118:Calcium