Oral manifestations of X-linked hypophosphatemic rickets: diagnostic and therapeutic strategies from the perspective of systemic homeostatic imbalance

Abstract X-linked hypophosphatemia (XLH) is a hereditary disorder caused by dysregulation of the FGF23-kidney-bone/teeth axis, leading to chronic hypophosphatemia and impaired mineralization. As target organs highly sensitive to phosphate homeostasis, the teeth and jaw often exhibit pathological changes that precede skeletal deformities, offering early diagnostic value. This article elucidates the damaging effects of hypophosphatemia on dental hard tissues and craniofacial development. Hypophosphatemia-induced impaired dentin mineralization results in interglobular dentin retention and abnormal pulp morphology, which, together with enamel microcracks, constitute the pathological basis for spontaneous pulp infections and periapical lesions. Craniofacial manifestations also include jaw abnormalities, periodontal bone loss, and craniosynostosis. A diagnostic framework for XLH-related oral manifestations integrating imaging, biochemical markers, and genetic testing is proposed, with key differential diagnoses clarified. The article emphasizes the paradigm shift in managing XLH-associated oral complications from conventional phosphate/vitamin D supplementation to anti-FGF23 targeted therapy. It advocates for life-cycle oral management coordinated with systemic homeostatic reconstruction for XLH encompassing prevention, infection control, and multidisciplinary care. By integrating systemic etiological intervention with local precision therapy, this review aims to provide a basis for early identification and standardized management of XLH.