Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo-controlled study

J Clin Endocrinol Metab. 2011 Feb;96(2):355-64. doi: 10.1210/jc.2010-0636. Epub 2010 Nov 24.

Abstract

Context: 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.

Design and participants: 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.

Main outcome measures: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alendronate / adverse effects
  • Alendronate / therapeutic use*
  • Bone Density
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism
  • Child
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Fracture Healing / drug effects
  • Fractures, Bone / epidemiology
  • Humans
  • Ilium / diagnostic imaging
  • Ilium / pathology
  • Male
  • Muscle Strength / physiology
  • Osteogenesis Imperfecta / drug therapy*
  • Osteogenesis Imperfecta / metabolism
  • Osteogenesis Imperfecta / pathology
  • Pain / etiology
  • Patient Compliance
  • Radiography
  • Self Care
  • Spine / diagnostic imaging

Substances

  • Bone Density Conservation Agents
  • Alendronate