title: Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo-controlled study.
abstract: BACKGROUND
  Information on the use of oral bisphosphonate agents to treat pediatric osteogenesis imperfecta (OI) is limited.
  
  
  OBJECTIVE
  The objective of the investigation was to study the efficacy and safety of daily oral alendronate (ALN) in children with OI.
  
  
  METHODS
  We conducted a multicenter, double-blind, randomized, placebo-controlled study. One hundred thirty-nine children (aged 4-19 yr) with type I, III, or IV OI were randomized to either placebo (n = 30) or ALN (n = 109) for 2 yr. ALN doses were 5 mg/d in children less than 40 kg and 10 mg/d for those 40 kg and greater.
  
  
  METHODS
  Spine areal bone mineral density (BMD) z-score, urinary N-telopeptide of collagen type I, extremity fracture incidence, vertebral area, iliac cortical width, bone pain, physical activity, and safety parameters were measured.
  
  
  RESULTS
  ALN increased spine areal BMD by 51% vs. a 12% increase with placebo (P < 0.001); the mean spine areal BMD z-score increased significantly from -4.6 to -3.3 (P < 0.001) with ALN, whereas the change in the placebo group (from -4.6 to -4.5) was insignificant. Urinary N-telopeptide of collagen type I decreased by 62% in the ALN-treated group, compared with 32% with placebo (P < 0.001). Long-bone fracture incidence, average midline vertebral height, iliac cortical width, bone pain, and physical activity were similar between groups. The incidences of clinical and laboratory adverse experiences were also similar between the treatment and placebo groups.
  
  
  CONCLUSIONS
  Oral ALN for 2 yr in pediatric patients with OI significantly decreased bone turnover and increased spine areal BMD but was not associated with improved fracture outcomes.
authors.affiliation: Genetics Unit, Shriners Hospital for Children, 1529 Cedar Avenue, Montréal, Québec, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Ward
authors.forename: F
authors.initials: F
authors.lastname: Rauch
authors.forename: M P
authors.initials: MP
authors.lastname: Whyte
authors.forename: J
authors.initials: J
authors.lastname: D'Astous
authors.forename: P E
authors.initials: PE
authors.lastname: Gates
authors.forename: D
authors.initials: D
authors.lastname: Grogan
authors.forename: E L
authors.initials: EL
authors.lastname: Lester
authors.forename: R E
authors.initials: RE
authors.lastname: McCall
authors.forename: T A
authors.initials: TA
authors.lastname: Pressly
authors.forename: J O
authors.initials: JO
authors.lastname: Sanders
authors.forename: P A
authors.initials: PA
authors.lastname: Smith
authors.forename: R D
authors.initials: RD
authors.lastname: Steiner
authors.forename: E
authors.initials: E
authors.lastname: Sullivan
authors.forename: G
authors.initials: G
authors.lastname: Tyerman
authors.forename: D L
authors.initials: DL
authors.lastname: Smith-Wright
authors.forename: N
authors.initials: N
authors.lastname: Verbruggen
authors.forename: N
authors.initials: N
authors.lastname: Heyden
authors.forename: A
authors.initials: A
authors.lastname: Lombardi
authors.forename: F H
authors.initials: FH
authors.lastname: Glorieux
mesh_terms: D000293:Adolescent; D019386:Alendronate / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D017102:Fracture Healing / Q000187:drug effects; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D007085:Ilium / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D053580:Muscle Strength / Q000502:physiology; D010013:Osteogenesis Imperfecta / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000209:etiology; D010349:Patient Compliance; D011859:Radiography; D012648:Self Care; D013131:Spine / Q000000981:diagnostic imaging
chemical_list: D050071:Bone Density Conservation Agents; D019386:Alendronate