Nishizawa, C.; Miura, J.; Iwayama, T.; Yamazaki, M.; Michigami, T.; Miyagawa, K.

Objective: X-linked hypophosphatemia (XLH) is associated with dental complications, including spontaneous endodontic infections (abscesses) in non-carious teeth and severe periodontal loss. Although previous studies have mainly emphasized dentin hypomineralization, the structural basis underlying periodontal tissue failure remains incompletely understood. In this study, we investigated histoanatomical abnormalities in the dentin and periodontium of Hyp mice to clarify the structural consequences of Phex deficiency in adult molars. Methods: Detailed histological and scanning electron microscopy (SEM) analyses were performed on the molar regions of untreated adult Hyp mice and wild-type littermates, with particular attention to the structural integrity of the root and periodontal ligament (PDL). Odontoblast process morphology and periodontal attachment abnormalities were also evaluated. Results: Hyp molars exhibited marked structural abnormalities in the root region, including radicular shunt-like defects and disorganization of odontoblast processes, which were more evident in the furcation and radicular dentin than in the crown. In addition, we identified a characteristic asymmetry in periodontal attachment: detachment of the PDL from the cementum surface was frequently observed, whereas attachment to the alveolar bone surface was relatively preserved. These abnormalities were accompanied by thinning and discontinuity of Sharpey's fibers, increased vascularity, and accumulation of CD31-positive cells in the PDL. Conclusions: Our findings expand the current understanding of XLH oral pathology by indicating that, in addition to dentin and enamel hypomineralization, XLH involves structural defects in root formation and periodontal attachment. This study provides a histoanatomical framework for understanding refractory dental complications in XLH and further supports the importance of intervention during the period of root development.