title: Changes to the cell, tissue and architecture levels in cranial suture synostosis reveal a problem of timing in bone development.
abstract: Premature fusion of cranial sutures is a common problem with an incidence of 3-5 per 10,000 live births. Despite progress in understanding molecular/genetic factors affecting suture function, the complex process of premature fusion is still poorly understood. In the present study, corresponding excised segments of nine patent and nine prematurely fused sagittal sutures from infants (age range 3-7 months) with a special emphasis on their hierarchical structural configuration were compared. Cell, tissue and architecture characteristics were analysed by transmitted and polarised light microscopy, 2D-histomorphometry, backscattered electron microscopy and energy-dispersive-x-ray analyses. Apart from wider sutural gaps, patent sutures showed histologically increased new bone formation compared to reduced new bone formation and osseous edges with a more mature structure in the fused portions of the sutures. This pattern was accompanied by a lower osteocyte lacunar density and a higher number of evenly mineralised osteons, reflecting pronounced lamellar bone characteristics along the prematurely fused sutures. In contrast, increases in osteocyte lacunar number and size accompanied by mineralisation heterogeneity and randomly oriented collagen fibres predominantly signified woven bone characteristics in patent, still growing suture segments. The already established woven-to-lamellar bone transition provides evidence of advanced bone development in synostotic sutures. Since structural and compositional features of prematurely fused sutures did not show signs of pathological/defective ossification processes, this supports the theory of a normal ossification process in suture synostosis - just locally commencing too early. These histomorphological findings may provide the basis for a better understanding of the pathomechanism of craniosynostosis, and for future strategies to predict suture fusion and to determine surgical intervention.
authors.affiliation: Department of Neurological Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Regelsberger
authors.forename: P
authors.initials: P
authors.lastname: Milovanovic
authors.forename: T
authors.initials: T
authors.lastname: Schmidt
authors.forename: M
authors.initials: M
authors.lastname: Hahn
authors.forename: E A
authors.initials: EA
authors.lastname: Zimmermann
authors.forename: M
authors.initials: M
authors.lastname: Tsokos
authors.forename: J
authors.initials: J
authors.lastname: Zustin
authors.forename: R O
authors.initials: RO
authors.lastname: Ritchie
authors.forename: M
authors.initials: M
authors.lastname: Amling
authors.forename: B
authors.initials: B
authors.lastname: Busse
mesh_terms: D001846:Bone Development; D002113:Calcification, Physiologic; D016022:Case-Control Studies; D003393:Cranial Sutures / Q000473:pathology*; D006253:Haversian System / Q000166:cytology; D006801:Humans; D007223:Infant; D010011:Osteocytes / Q000166:cytology; D013580:Synostosis / Q000209:etiology* / Q000473:pathology*