Craniofacial Bone Mineral Density in Mice with Osteogenesis Imperfecta




McBride, Alexandra H.


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Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by the abnormal synthesis and assembly of type I collagen, 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 type I collagen defects, as seen in OI type III, affect BMD within the craniofacial skeleton; (2) to determine whether BMD varies among specific region of the craniofacial skeleton; (3) to examine whether diet-related variation in biomechanical loading is related to higher craniofacial BMD. 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-soft (n=3), OIM-hard (n=6), WT-soft (n=3), and WT-hard (n=9). 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 genotypes (α = 0.100). When controlling for diet, WT mice had significantly greater BMD values than OIM mice at each ROI except at the maxilla at M2. Although variation between treatment groups, a general trend for increased BMD in "high" strain regions, such as the mandibular symphysis or the maxillary incisor, existed. Lastly, WT mice raised on a hard diet were observed to have the highest BMD measurements across each region the craniofacial skeleton, however no significant differences were observed between OIM-/- mice raised on hard versus soft diets. These results suggest that craniofacial BMD is generally lower in individuals with type I collagen defects, consistent with the post-cranial presentation. Additionally, regions associated with high strain during routine masticatory loading exhibited increased BMD as compared to regions of the skull that experience relatively "low" strain during chewing. While diet-associated loading may influence craniofacial BMD, in this study type I collagen status appears to be the primary determinant of BMD.