Craniofacial Bone Mineral Density During Growth in Mice with Osteogenesis Imperfecta (OI)

Purpose: Osteogenesis imperfecta(OI) is a genetic connective tissue defect resulting in fragile bones due to mutations affecting formation of type I collagen. Low bone mineral density (BMD) in the post-cranial skeleton has been reported in human patients and murine models with OI, yet little is known about craniofacial biomineralization in the disorder. Typically, skeletal mineralization is responsive to the strain environment. The aim of this study is to investigate longitudinal changes in craniofacial BMD in a mouse model of OI type III (most severe form), and to quantify BMD in regions relative to feeding biomechanical forces. Methods: Homozygous recessive OI murine (OIM), a mouse strain with a COL1A2 mutation modeling OI type III, and unaffected wild-type (WT) littermates were micro-CT scanned at weeks 4, 10, and 16. BMD in eight regions was analyzed using Bruker CTAnalyzer software and Mann-Whitney U tests. Results: OIM mice had significantly (p< 0.05) lower BMD than WT mice in all eight regions during week 4, no significant differences in week 10, and significant differences at the parietal bone, mandibular symphysis, and maxillary incisor regions during week 16. Absolute BMD was higher within regions proximal to the bite point at skeletal maturity. Conclusions: These results support a trend that OIM mice have lower BMD in the craniofacial skeleton compared to WT mice throughout growth and BDM in all mice is affected by proximity to bite forces. Understanding craniofacial mineralization patterns in OI could assist in the implementation of pharmaceutical interventions to increase BMD.