title: Pamidronate treatment of osteogenesis imperfecta--lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response.
abstract: Severe forms of osteogenesis imperfecta (OI) are characterised by osteoporosis with multiple fractures, deformity, progressive loss of mobility and chronic bone pain. Bisphosphonates, as osteoclast inhibitors, reduce bone turnover and improve osteoporosis.
  
  
  OBJECTIVE
  To investigate the effect of pamidronate treatment of severe OI in children, and find any correlation between clinical severity, age at start of treatment, type of predicted collagen mutation and treatment response.
  
  
  METHODS
  Open, observational trial.
  
  
  METHODS
  A two-year study of pamidronate treatment was undertaken in a cohort of 18 children, (1.4-14.5 years) with OI types III and IV.
  
  
  METHODS
  Disodium pamidronate, 1 mg/kg/day for 3 days every 4 months, by i.v. infusion with measurement of bone turnover, bone density, vertebral morphology and skin biopsies to assess collagen mutation.
  
  
  RESULTS
  Eleven children have completed 2 years of treatment and three more have completed 20 months. Sustained cessation of bone pain, improved mobility and decreased fracture rate were seen in all patients. Bone turnover decreased slightly but was not statistically significant. Bone mineral density (BMD) of lumbar spine increased by a mean of 124.7 +/- 75.7% over 2 years (Z score mean -5.08 +/- 1.27, to -3.30 +/- 1.71, p <0.001); the greatest change in BMD was seen in the most severely affected patients: 138 +/- 50.6% (severe), 62.47 +/- 22.9% (mild). There was a mean increase in vertebral height at L4 of 68.5% and in vertebral area of 85.4%. The majority of patients had slow electrophoretic migration of type I collagen alpha chains or reduced secretion of type I collagen, indicative of structural, helix-breaking mutations. There was no correlation between phenotypic severity, age at start of treatment and treatment response (r2 = 0.14)
  
  
  CONCLUSIONS
  Pamidronate treatment of severe forms of OI is an effective therapeutic modality to increase bone density, decrease fracture rate, increase mobility and improve quality of life, irrespective of the severity of the mutation or clinical phenotype. It has a good short-term safety profile.
authors.affiliation: Department of Endocrinology and Diabetes, Royal Children's Hospital, Parkville, Victoria, Australia. zacharim@cryptic.rch.unimelb.edu.au
authors.forename: Margaret
authors.initials: M
authors.lastname: Zacharin
authors.forename: John
authors.initials: J
authors.lastname: Bateman
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015519:Bone Density; D016723:Bone Remodeling; D002118:Calcium / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000235:genetics*; D024042:Collagen Type I / Q000235:genetics; D004164:Diphosphonates / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007668:Kidney / Q000000981:diagnostic imaging; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000188:drug therapy* / Q000503:physiopathology*; D000077268:Pamidronate; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D024042:Collagen Type I; D004164:Diphosphonates; D003094:Collagen; D000077268:Pamidronate; D002118:Calcium