Elevated fibroblast growth factor 23 (FGF23) in X-linked hypophosphatemia (XLH) results in rickets and phosphate wasting, manifesting by severe bone and dental abnormalities. Burosumab, a FGF23-neutralizing antibody, an alternative to conventional treatment (phosphorus and active vitamin D analogs), showed significant improvement in the long bone phenotype. Here, we examined whether FGF23 antibody (FGF23-mAb) also improved the dentoalveolar features associated with XLH. Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg⁻¹ of FGF23-mAb for 2 months and compared to wild-type (WT) and vehicle (PBS) treated Hyp mice (n = 3–7 mice). Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice, the higher concentration resulting in a rescue similar to WT levels. FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones. Histology revealed improved mineralization of the dentoalveolar tissues, with a decreased amount of osteoid, predentin and cementoid. Better periodontal ligament attachment was also observed, evidenced by restoration of the acellular cementum. These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features. Taken together, our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment, heralding its benefit in clinics for dental abnormalities.

X 连锁低磷血症 (XLH) 中成纤维细胞生长因子 23 (FGF23) 升高会导致佝偻病和磷酸盐消耗，表现为严重的骨骼和牙齿异常。Burosumab 是一种 FGF23 中和抗体，是传统治疗（磷和活性维生素 D 类似物）的替代品，显示出长骨表型的显着改善。在这里，我们检查了 FGF23 抗体 (FGF23-mAb) 是否也改善了与 XLH 相关的牙槽特征。四周大的雄性Hyp小鼠每周注射 4 或 16 mg·kg ^-1 FGF23-mAb，持续 2 个月，并与野生型 (WT) 和媒介物 (PBS) 治疗的Hyp小鼠进行比较（n  = 3–7老鼠）。Micro-CT 分析表明，两种剂量的 FGF23-mAb 均可恢复Hyp小鼠的牙本质/牙骨质体积并纠正扩大的牙髓体积，较高浓度导致与 WT 水平相似的救援效果。与载体治疗相比，FGF23-mAb 治疗还改善了牙槽骨体积分数和矿物质密度。组织学显示牙槽组织的矿化得到改善，类骨质、前牙本质和类牙骨质的量减少。还观察到更好的牙周韧带附着，这通过无细胞牙骨质的恢复得到证明。这些临床前数据与两名 XLH 患者的回顾性分析一致，表明 burosumab 治疗改善了口腔特征。总而言之，我们的数据表明，FGF23-mAb 治疗极大地改善了牙槽组织，预示着其在临床上治疗牙齿异常的益处。