Changes in cranial base and craniocervical junction during growth in healthy individuals and in patients with Osteogenesis imperfecta

4 Contents 6 List of original publications 8 Abbreviations 9 1. Introduction 11 2. Review of the literature 12 2.1. Bone metabolism and growth 12 2.2. Neurocranium and craniocervical junction 15 2.2.1. Anatomy 15 2.2.2. Prenatal development 16 2.2.3. Postnatal development 20 2.3. Osteogenesis imperfecta 23 2.3.1. Molecular basis 23 2.3.2. Clinical features 26 2.3.3. Treatment 31 2.4. Basilar pathology 32 2.4.1. Pathology of craniocervical junction 34 2.4.2. Platybasia 36 2.4.3. Basilar pathology in OI 37 2.4.4. Basilar pathology in other disorders 39 2.4.5. Treatment 41 3. Aims of the study 42 4. Materials and methods 43 4.1. Diagnostic images 43 7 4.1.1. Normal population cohorts 43 4.1.2. OI patient cohorts 45 4.2. Radiographic measurements 46 4.2.1. Intraand interexaminer error 49 4.3. Other measurements 49 4.4. Statistical methods 49 4.5. Ethical considerations 50 5. Results 51 5.1. Validation of methods 51 5.2. Basilar structures in normal population 52 5.3. Basilar structures in OI 54 5.3.1. Cross-sectional analysis 54 5.3.2. Longitudinal analysis 56 6. Discussion 63 6.1. Reliability of observations 63 6.2. Radiographic evaluation of cranial base dimensions 64 6.3. Natural course of basilar pathology 65 7. Conclusions 70 8. Clinical recommendations and future considerations 72 9. Acknowledgements 73 10. References 75 11. Original publications 95 List of original publications This thesis is based on the following publications, referred to in the text by their roman numerals. This thesis also contains some unpublished data. I Arponen H, Elf H, Evälahti M, Waltimo-Sirén J 2008 Reliability of cranial base measurements on lateral skull radiographs. Orthod Craniofac Res 4:201-210. II Arponen H, Evälahti M, Waltimo-Sirén J 2010 Dimensions of the craniocervical junction in longitudinal analysis of normal growth. Child’s Nervous System 26:763-769. III Cheung M, Arponen H, Roughley P, Azouz M, Glorieux FH, Waltimo-Sirén J, Rauch F 2011 Cranial Base Abnormalities in Osteogenesis Imperfecta: Phenotypic and Genotypic Determinants. J Bone Min Res 26:405-413. IV Arponen H, Mäkitie O, Haukka J, Ranta H, Ekholm M, Mäyränpää MK, Kaitila I, Waltimo-Sirén J 2012 Prevalence and natural course of craniocervical junction anomalies during growth in patients with osteogenesis imperfecta. J Bone Min Res 27: 1142–1149. Original publications are reprinted with the permission of the publisher. The final publication of study II is available at www.springerlink.com. Studies III and IV, are reproduced from J Bone Miner Res with permission of the American Society for Bone and Mineral Research.