Craniofacial Effects of Zoledronic Acid on the Osteogenesis Imperfecta Mouse (-/-) Model of Severe Osteogenesis Imperfecta

Background: Osteogenesis imperfecta (OI) is a rare genetic disorder affecting mainly type I collagen, which leads to bone fragility and deformities. OI patients also present craniofacial abnormalities such as macrocephaly and malocclusion. Recently, craniofacial dysmorphism was highlighted in the osteogenesis imperfecta mouse (oim), a validated model of the most severe form of OI. This study explores the impact of zoledronic acid (ZA), commonly administered to OI patients to increase bone mass and mechanical strength, on oim craniofacial structure. Methods: Fifteen oim received a single intravenous ZA injection (100 mu g/kg) at 5 weeks (ZA group), while fifteen remained untreated (control). Before euthanasia at 14 weeks, in vivo computed tomography provided craniometric data. Post-euthanasia, heads underwent peripheral Quantitative Computed Tomography (pQCT); coronal decalcified sections through temporomandibular joints were analyzed (n = 6/mouse) after Masson's trichrome staining (3 sections) or under polarized light to study collagen birefringence (3 sections). Results: In vivo craniometry highlighted the positive effect on vertical growth in ZA oim models as compared to untreated ones, with significant increases in mandibular length and incisor height and without any change in transversal dimensions. The pQCT scans showed the significantly higher total mineral density and cortical mineral density of the mandibular ramus in the ZA than the untreated group. Via microscopic analysis, the cranial vault was thicker and the collagen birefringence was higher in the ZA group than in the untreated group, but differences were not significant. Conclusion: To conclude, ZA had some beneficial effects on craniofacial vertical height and ramus density and, to a lower extent, on vault thickness, while transversal dimensions did not seem to be influenced by ZA intake. These data emphasize the need to consider the whole skeleton when treating OI patients.