title: First use of the RANKL antibody denosumab in osteogenesis imperfecta type VI.
abstract: Osteogenesis imperfecta (OI) is a genetically heterogeneous disease leading to bone fragility. OI-VI is an autosomal-recessive form caused by mutations in SERPINF1. There is experimental evidence suggesting that loss of functional SERPINF1 leads to an activation of osteoclasts via the RANK/RANKL pathway. Patients with OI-VI show a poor response to bisphosphonates. We report on four children with OI-VI who had shown continuously elevated urinary bone resorption markers during a previous treatment with bisphosphonates. We treated these children with the RANKL antibody denosumab to reduce bone resorption.
  
  
  RESULTS
  Denosumab (1 mg/kg body weight) was injected s.c. every 3 months. There were no severe side effects. Markers of bone resorption decreased to the normal range after each injection. N-terminal Propeptide of collagen 1 was measured in the serum during the first treatment cycle and decreased also. Urinary deoxypyridinoline/creatinine was monitored in a total of seven treatment cycles and indicated that bone resorption reached the pre-treatment level after 6-8 weeks.
  
  
  CONCLUSIONS
  This was the first use of denosumab in children with OI-VI. Denosumab was well tolerated, and laboratory parameters provided evidence that the treatment reversibly reduced bone resorption. Therefore, denosumab may be a new therapeutic option for patients with OI-VI.
authors.affiliation: Children's Hospital, University of Cologne, 50931 Cologne, Germany. joerg.semler@uk-koeln.de
authors.forename: O
authors.initials: O
authors.lastname: Semler
authors.forename: C
authors.initials: C
authors.lastname: Netzer
authors.forename: H
authors.initials: H
authors.lastname: Hoyer-Kuhn
authors.forename: J
authors.initials: J
authors.lastname: Becker
authors.forename: P
authors.initials: P
authors.lastname: Eysel
authors.forename: E
authors.initials: E
authors.lastname: Schoenau
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002648:Child; D000069448:Denosumab; D006801:Humans; D008297:Male; D010013:Osteogenesis Imperfecta / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053245:RANK Ligand / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab