title: Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement.
abstract: Bisphosphonates have been widely administered to children with OI based on observational trials. A randomized controlled trial of q3m intravenous pamidronate in children with types III and IV OI yielded positive vertebral changes in DXA and geometry after 1 year of treatment, but no further significant improvement during extended treatment. The treated group did not experience significantly decreased pain or long bone fractures or have increased motor function or muscle strength.
  
  
  BACKGROUND
  Bisphosphonates, antiresorptive drugs for osteoporosis, are widely administered to children with osteogenesis imperfecta (OI). Uncontrolled pamidronate trials in OI reported increased BMD, vertebral coronal area, and mobility, and decreased pain. We conducted a randomized controlled trial of pamidronate in children with types III and IV OI.
  
  
  METHODS
  This randomized trial included 18 children (4-13 years of age) with types III and IV OI. The first study year was controlled; 9 children received pamidronate (10 mg/m2/day IV for 3 days every 3 months). Four children in each group also received recombinant growth hormone (rGH) injections (0.06 mg/kg/day for 6 days/week). Seven children in the treatment group received pamidronate for an additional 6-21 months. All patients had L1-L4 DXA, spine QCT, spine radiographs, and musculoskeletal and functional testing.
  
  
  RESULTS
  In the controlled phase, treated patients experienced a significant increase in L1-L4 DXA z score (p < 0.001) and increased L1-L4 mid-vertebral height (p = 0.014) and total vertebral area (p = 0.003) compared with controls. During extended treatment, DXA z scores and vertebral heights and areas did not increase significantly beyond the 12-month values. Fracture rate decreased significantly in the upper extremities (p = 0.04) but not the lower extremities (p = 0.09) during the first year of treatment. Gross motor function, muscle strength, and pain did not change significantly during the controlled or extended treatment phases.
  
  
  CONCLUSIONS
  A controlled trial confirmed the spine benefits of short-term pamidronate treatment in children with types III and IV OI. Pamidronate increased L1-L4 vertebral DXA and decreased vertebral compressions and upper extremity fractures. Vertebral measures did not improve during the extended treatment phase. The treatment group did not experience decreased lower extremity long bone fractures, significant improvement in growth, ambulation, muscle strength, or pain. There was substantial variability in individual response to treatment.
authors.affiliation: Section on Connective Tissue Disorders, BEMB, NICHD, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Anne D
authors.initials: AD
authors.lastname: Letocha
authors.forename: Holly L
authors.initials: HL
authors.lastname: Cintas
authors.forename: James F
authors.initials: JF
authors.lastname: Troendle
authors.forename: James C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Cann
authors.forename: Edith J
authors.initials: EJ
authors.lastname: Chernoff
authors.forename: Suvimol C
authors.initials: SC
authors.lastname: Hill
authors.forename: Lynn H
authors.initials: LH
authors.lastname: Gerber
authors.forename: Joan C
authors.initials: JC
authors.lastname: Marini
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001827:Body Height; D015519:Bone Density; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003720:Densitometry; D004164:Diphosphonates / Q000627:therapeutic use*; D050723:Fractures, Bone / Q000517:prevention & control; D013006:Growth Hormone / Q000627:therapeutic use; D006801:Humans; D010013:Osteogenesis Imperfecta / Q000188:drug therapy*; D000077268:Pamidronate; D013131:Spine / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D004164:Diphosphonates; D013006:Growth Hormone; D000077268:Pamidronate