title: Zoledronic acid in children with osteogenesis imperfecta and Bruck syndrome: a 2-year prospective observational study.
abstract: Treatment with zoledronic acid (ZA) over 2 years, among 33 children with osteogenesis imperfecta (OI) and five Bruck syndrome cases, showed reduction in fracture rates, pain, and improvement in bone mineral density (BMD) and motor milestones of development. This is the first study reporting the use of bisphosphonates in patients with Bruck syndrome (BS).
  
  
  BACKGROUND
  OI and BS are genetic disorders that result in bone fragility and reduced BMD. There is little literature describing the efficacy and safety of ZA in this population. In this study, we assess the response to treatment with ZA at six monthly intervals in Egyptian children with OI and BS for a period of 2 years.
  
  
  METHODS
  Thirty-three patients with OI and five patients with BS were treated with 0.1 mg/kg ZA intravenously every 6 months for 2 years during which they were followed up using different parameters. A clinical severity score (CSS) was applied to the patients before and 2 years after the start of therapy. Comparison of disease severity and response to ZA treatment between autosomal-dominant (AD) and autosomal-recessive (AR) OI patients was also done.
  
  
  RESULTS
  After 6 months of treatment, OI and BS patients showed a significant increase in BMD Z-scores (P < 0.003 in the spine and P < 0.004 in the hip), together with a significant drop in fracture rate (P < 0.001), relief of pain (P < 0.001), and improvement in ambulation (P < 0.001). CSS was significantly reduced after 2 years of treatment in both OI and BS patients. AR-OI patients were more severely affected than AD-OI patients and showed more significant improvement.
  
  
  CONCLUSIONS
  Zoledronic acid proved to be safe and effective in the treatment of OI and BS. The biannual infusion protocol was convenient to patients. There was a positive correlation between disease severity and benefits of the treatment. The use of the CSS proved to be of value in the assessment of the degree of severity in OI, and with some modifications, it was a valuable tool for the assessment of response to treatment.
authors.affiliation: Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt. ghadaotaify@yahoo.com.
authors.forename: G A
authors.identifier: http://orcid.org/0000-0003-2313-7387
authors.initials: GA
authors.lastname: Otaify
authors.affiliation: Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: M S
authors.initials: MS
authors.lastname: Aglan
authors.affiliation: Department of Biochemical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: M M
authors.initials: MM
authors.lastname: Ibrahim
authors.affiliation: Department of Medical Studies, Institute of Postgraduate Childhood Studies, Ain Shams University, Cairo, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Elnashar
authors.affiliation: Department of Biological Anthropology, Medical Division, National Research Centre, Cairo, Egypt.
authors.forename: R A S
authors.initials: RA
authors.lastname: El Banna
authors.affiliation: Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: S A
authors.initials: SA
authors.lastname: Temtamy
mesh_terms: D000293:Adolescent; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D010013:Osteogenesis Imperfecta / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D011446:Prospective Studies; D012720:Severity of Illness Index; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Bisphosphonates; Bruck syndrome; Clinical severity score; Osteogenesis imperfecta; Zoledronic acid