title: Childhood Osteoporosis and Presentation of Two Cases with Osteogenesis Imperfecta Type V.
abstract: BACKGROUND
  Osteogenesis imperfecta (OI) is etiologically heterogeneous disorder characterized by childhood osteoporosis. A subtype OI type V is caused by the same c.-14C>T mutation in the IFITM5 gene. Nevertheless, there is a marked interindividual phenotypic variability in clinical presentation; however, response to bisphosphonates is reported to be good.
  
  
  METHODS
  Two individuals with OI type V had multiple recurrent fractures with hypertrophic calluses, scoliosis and ossifications of the forearm interosseous membranes. Sequencing of IFITM5, genotyping of variants rs2297480 in farnesyl diphosphate synthase gene (FDPS), and rs3840452 in geranylgeranyl diphosphate synthase 1 gene (GGPS1), both involved in bisphosphonate metabolism, was performed.
  
  
  RESULTS
  In patient 1 BMD reached normal values during bisphosphonate treatment and remained normal four years after the treatment discontinuation. In patient 2 no increase in BMD after five years of bisphosphonate treatment was observed and callus formation continued. The c.-14C>T IFITM5 mutation in heterozygous state was detected in both individuals. Additionally, both patients carried FDPS variant rs2297480 in homozygous state, and were heterozygous for GGPS 1 variant rs3840452.
  
  
  CONCLUSIONS
  The paper presents a short overview of childhood osteoporosis with a special emphasis on OI type V by presenting two cases. Both OI type V patients had identical disease-causing mutation, but marked interindividual phenotypic variability. The striking failure in response to bisphosphonate treatment in one of the patients could not be explained by the variants in genes involved in bisphosphonate metabolism.
authors.affiliation: University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, Bohoriceva 20, 1000 Ljubljana, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Bratanic
authors.affiliation: University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, Bohoriceva 20, 1000 Ljubljana, Slovenia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Dzodan
authors.affiliation: University Medical Centre Ljubljana, University Children's Hospital, Unit for Special Laboratory Diagnostics, Vrazov trg 1, 1000 Ljubljana, Slovenia; University of Ljubljana, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Trebusak Podkrajsek
authors.affiliation: University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, Bohoriceva 20, 1000 Ljubljana, Slovenia.
authors.forename: Sara
authors.initials: S
authors.lastname: Bertok
authors.affiliation: University of Ljubljana, Faculty of Farmacy, Askerceva 7, 1000 Ljubljana, Slovenia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ostanek
authors.affiliation: University of Ljubljana, Faculty of Farmacy, Askerceva 7, 1000 Ljubljana, Slovenia.
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
authors.affiliation: University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, Bohoriceva 20, 1000 Ljubljana, Slovenia; University of Ljubljana, Faculty of Medicine, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.affiliation: University Children's Hospital, Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, Bohoriceva 20, 1000 Ljubljana, Slovenia.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Avbelj Stefanija
keywords: IFITM5 gene; bisphosphonates; bone mineral density; hypertrophic callus