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

dc.contributor.authorLadd, Summer
dc.contributor.authorOrgan, Jason
dc.contributor.authorMenegaz, Rachel A.
dc.creatorMcBride, Alexandra H.
dc.creator.orcid0000-0002-7261-7873 (Menegaz, Rachel)
dc.description.abstractPurpose: Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by the abnormal synthesis and assembly of type I collagen (Col1), a major organic component of bone. Clinical manifestations of the severe OI type III include small body size, limb deformities, and low bone mineral density (BMD) within the post-cranial skeleton. OI type III often co-occurs with craniofacial defects, such as dentinogenesis imperfecta (DI). The goals of this study are: (1) to examine whether Col1 defects, as seen in OI type III, affect BMD within the craniofacial skeleton; (2) to examine whether craniofacial BMD covaries with diet-related biomechanical loading. Methods: The homozygous recessive murine mouse (OIM-/-) is a model for OI Type III. Similar to human OI patients, OIM-/- mice exhibit low post-cranial BMD, smaller body size, and DI. OIM-/- mice and WT littermates were weaned at 21 days and raised on either hard (high loading) or soft (low loading) diets. This resulted in four genotype x diet treatment groups: OIM-hard (n=6), OIM-soft (n=3), WT-hard (n=9), and WT-soft (n=3). Micro-CT scans were collected at 16 weeks (skeletal maturity). BMD was measured using Bruker CTAnalyzer software for eight regions of interest (ROIs) within the mandible (TMJ, corpus at the second molar, and symphysis), facial skeleton (nasal bone, maxilla at the second molar, premaxilla at the incisor), and cranial vault (frontal and parietal bones). Pairwise Mann-Whitney U tests were used to statistically compare BMD between treatments (α = 0.05). Results: At all ROIs except for the frontal bone, WT-hard mice had significantly (p p = 0.052) with the current sample sizes. Similarly, at the mandibular and cranial vault ROIs, WT-soft mice tended to have higher BMD than OIM-hard and/or OIM-soft mice (p Conclusions: These results suggest that craniofacial BMD is generally lower in individuals with Col1 defects, consistent with the postcranial presentation. WT mice raised on a hard diet were observed to have the highest BMD measurements across the craniofacial skeleton, however no significant differences were observed between OIM-/- mice raised on hard versus soft diets. While diet-associated loading may influence craniofacial BMD, in this study Col1 status appears to be the primary determinant of BMD.
dc.titleCraniofacial Bone Mineral Density in Mice with Osteogenesis Imperfecta (OI)