title: Pamidronate in children and adolescents with osteogenesis imperfecta: effect of treatment discontinuation.
abstract: BACKGROUND
  Cyclical iv pamidronate is a widely used symptomatic therapy of osteogenesis imperfecta (OI). What happens after treatment discontinuation is unknown.
  
  
  OBJECTIVE
  The objective of this study was to assess the effect of pamidronate discontinuation in pediatric patients with moderate to severe OI types I, III, and IV.
  
  
  METHODS
  This was an open-label controlled and observational study in patients who had received pamidronate for more than 3 yr.
  
  
  METHODS
  This study was performed at a pediatric metabolic bone research unit.
  
  
  METHODS
  In the controlled study, 12 pairs of patients were matched for age, OI severity, and duration of pamidronate treatment. Pamidronate was stopped in one patient of each pair; the other continued to receive treatment. In the observational study, 38 OI patients were examined (mean age, 13.8 yr).
  
  
  METHODS
  The intervention was discontinuation of pamidronate treatment for 2 yr.
  
  
  METHODS
  The main outcome measures were lumbar spine bone mineral content and areal bone mineral density (aBMD), biochemical markers of bone metabolism, fracture incidence, and clinical evaluation.
  
  
  RESULTS
  In the controlled study, bone resorption activity was higher after treatment discontinuation. Bone mineral content continued to increase in both groups. aBMD z-scores decreased in the untreated group, but increased in the continuation cohort. Fracture rates and functional status were similar between groups. In the observational study, bone resorption activity increased after treatment discontinuation, but remained significantly lower than in untreated OI patients. Bone mineral content and aBMD continued to increase, whereas aBMD z-scores decreased. Changes were faster in patients who continued growing.
  
  
  CONCLUSIONS
  Bone metabolism is still suppressed 2 yr after pamidronate discontinuation. Bone mass gains continue after treatment is stopped, but lumbar spine aBMD increases less than in healthy subjects. The size of these effects is growth dependent.
authors.affiliation: Genetics Unit, Shriners Hospital for Children, 1529 Cedar Avenue, Montréal, Québec, Canada H3G 1A6. frauch@shriners.mcgill.ca
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
authors.forename: Craig
authors.initials: C
authors.lastname: Munns
authors.forename: Christof
authors.initials: C
authors.lastname: Land
authors.forename: Francis H
authors.initials: FH
authors.lastname: Glorieux
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001862:Bone Resorption / Q000453:epidemiology; D001842:Bone and Bones / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000077268:Pamidronate; D011859:Radiography; D013131:Spine / Q000033:anatomy & histology
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077268:Pamidronate