Impact of oral phosphate supplements and active vitamin D treatment on dentoalveolar features of X-linked hypophosphatemia

Abstract X-linked hypophosphatemia (XLH), the most common form of genetic rickets (1/20000 births), results in the disruption of skeletal and dental mineralization. Oral features include dentinomalacia, spontaneous dental abscesses, and a high susceptibility to periodontitis. The association of phosphate supplementation and active vitamin D analogs (PO4/VitD) aims to counteract the consequences of FGF23 excess and the impaired production of active vitamin D. Despite a significant improvement in the long bone phenotype, the impact on dentoalveolar tissues remains poorly documented. Here, we aimed to determine whether the PO4/VitD treatment improves dental features in the Hyp mouse model of XLH and in XLH patients. Hyp mice were treated with oral phosphate supplementation and calcitriol injections from 3 wk to 3 mo and were compared with untreated Hyp and WT mice. Histological analyses were also performed on teeth from patients with XLH treated with PO4/VitD and on control teeth. Micro-CT analyses showed that the PO4/VitD treatment did not significantly correct dentin/cementum volume and density, pulp chamber enlargement, and alveolar bone parameters in Hyp mice. Histological analyses also revealed that dentinomalacia and periodontal attachment were not rescued by the treatment. Remarkably, permanent teeth from XLH patients treated with PO4/VitD during childhood displayed a significant reduction in predentin thickness and a thinner layer of globular dentin. Taken together, our data show that the PO4/VitD treatment does not significantly improve dentoalveolar features in Hyp mice treated at the prepubertal stage. However, the impact observed on dentin in human teeth supports the interest of this treatment regarding the occurrence of spontaneous dental abscesses.