title: Safety and efficacy of denosumab in children with osteogenesis imperfect--a first prospective trial.
abstract: OBJECTIVE
  Osteogenesis imperfecta (OI) is a rare hereditary disease leading to bone fragility. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. Aim of this study was a 48-week, open-label, pilot study of the safety and efficacy of denosumab in 10 children with OI.
  
  
  METHODS
  Ten patients (age range: 5.0-11.0 years; at least two years of prior bisphosphonate treatment) with genetically confirmed OI were studied. Denosumab was administered subcutaneously every 12 weeks with 1 mg/kg body weight. Primary endpoint was change of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 48 weeks. Safety was assessed by bone metabolism markers and adverse event reporting.
  
  
  RESULTS
  Mean relative change of lumbar aBMD was +19 % (95%-CI: 7-31%). Lumbar spine aBMD Z-Scores increased from -2.23±2.03 (mean±SD) to -1.27±2.37 (p=0.0006). Mobility did not change (GMFM-88 +2.72±4.62% (p=0.16); one-minute walking test +11.00±15.82 m (p=0.15). No severe side effects occurred.
  
  
  CONCLUSIONS
  On average, there was a significant increase in lumbar spine aBMD percent change after 48 weeks of denosumab. There was no change in mobility parameters and no serious adverse events. Further trials are necessary to assess long-term side effects and efficacy.
authors.affiliation: Children's Hospital, University of Cologne, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hoyer-Kuhn
authors.forename: J
authors.initials: J
authors.lastname: Franklin
authors.forename: G
authors.initials: G
authors.lastname: Allo
authors.forename: M
authors.initials: M
authors.lastname: Kron
authors.forename: C
authors.initials: C
authors.lastname: Netzer
authors.forename: P
authors.initials: P
authors.lastname: Eysel
authors.forename: B
authors.initials: B
authors.lastname: Hero
authors.forename: E
authors.initials: E
authors.lastname: Schoenau
authors.forename: O
authors.initials: O
authors.lastname: Semler
mesh_terms: D015502:Absorptiometry, Photon; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000069448:Denosumab / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects; D008297:Male; D010013:Osteogenesis Imperfecta / Q000188:drug therapy*; D010865:Pilot Projects
chemical_list: D050071:Bone Density Conservation Agents; D000069448:Denosumab