Early life functional transitions impact craniofacial morphology in osteogenesis imperfecta

Early life behaviors have a profound role in shaping adult craniofacial morphology. During early life, all mammals undergo the dynamic transition from suckling to mastication, a period coinciding with rapid cranial biomineralization. Osteogenesis imperfecta (OI), a genetic disorder that impacts the production of type I collagen, disrupts biomineralization, leading to craniofacial growth differences affecting quality of life. This study investigates craniofacial development during infant oral motor developmental stages in OI mice compared to unaffected wild-type littermates (WT mice). We hypothesize OI mice will exhibit smaller overall size, and the adult OI phenotype will develop postnatally in response to masticatory loading. Point cloud and fixed landmarks were collected from micro-computed tomography scans, then geometric morphometric analyses and interlandmark distances (ILDs) compared craniofacial size and shape between OI and WT mice at birth (P0; n = 27 OI murine/20 WT) and postnatal Days 7 (P7; n = 21/21), 14 (P14; n = 16/20), 21 (P21; n = 20/26), and 28 (P28; n = 26/33). This study found no size and shape differences between genotypes at birth. Starting at P7, OI mice are significantly (p < 0.05) smaller and display pronounced shape changes (p < 0.001) characterized by a larger neurocranium and a shorter viscerocranium. At P21, significant differences emerge in cranial base orientation, neurocranial width, viscerocranial shortening, and zygomatic arch displacement. These findings underscore the importance of early life oral motor stages in developing the adult OI craniofacial phenotype and oral health, suggesting earlier craniofacial interventions may improve effective treatment of OI.