title: Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates.
abstract: OBJECTIVE
  Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI.
  
  
  METHODS
  In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average.
  
  
  RESULTS
  Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant.
  
  
  CONCLUSIONS
  These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology. Careful followup of cranial base morphology is warranted, particularly in patients with severe OI.
authors.affiliation: Department of Orthodontics, Institute of Dentistry, University of Helsinki;
authors.forename: Heidi
authors.initials: H
authors.lastname: Arponen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Vuorimies
authors.forename: Jari
authors.initials: J
authors.lastname: Haukka
authors.forename: Helena
authors.initials: H
authors.lastname: Valta
authors.forename: Janna
authors.initials: J
authors.lastname: Waltimo-Sirén
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
mesh_terms: D000293:Adolescent; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007223:Infant; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D010013:Osteogenesis Imperfecta / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077268:Pamidronate; D010985:Platybasia / Q000473:pathology*; D012189:Retrospective Studies; D000068296:Risedronic Acid; D019291:Skull Base / Q000473:pathology*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000068296:Risedronic Acid; D012968:Etidronic Acid; D000077268:Pamidronate
keywords: CM-I = Chiari malformation Type I; OI = osteogenesis imperfecta; basilar impression; basilar invagination; bisphosphonates; congenital; craniocervical junction; osteogenesis imperfecta