Dental impact of anti-fibroblast growth factor 23 therapy in X-linked hypophosphatemia.

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2023-12-06 DOI:10.1038/s41368-023-00259-8
Elis J Lira Dos Santos, Kenta Nakajima, Julien Po, Ayako Hanai, Volha Zhukouskaya, Martin Biosse Duplan, Agnès Linglart, Takashi Shimada, Catherine Chaussain, Claire Bardet
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Abstract

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.

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抗成纤维细胞生长因子 23 疗法对 X 连锁低磷血症患者牙齿的影响
X连锁低磷血症(XLH)中成纤维细胞生长因子23(FGF23)的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,可替代常规治疗(磷和活性维生素D类似物),对长骨表型有显著改善。在此,我们研究了 FGF23 抗体(FGF23-mAb)是否也能改善与 XLH 相关的齿槽特征。四周大的雄性 Hyp 小鼠每周注射 4 或 16 mg-kg-1 的 FGF23-mAb 达 2 个月,并与野生型(WT)和药物(PBS)治疗的 Hyp 小鼠(n = 3-7 只)进行比较。显微 CT 分析表明,两种剂量的 FGF23-mAb 都能恢复 Hyp 小鼠的牙本质/牙釉质体积,并纠正扩大的牙髓体积,较高浓度的 FGF23-mAb 能产生与 WT 水平相似的修复效果。与用药物治疗的小鼠相比,FGF23-mAb 还能改善牙槽骨体积分数和矿物质密度。组织学检查显示,牙槽骨组织的矿化程度有所提高,类骨质、predentin 和 cementoid 的数量有所减少。牙周韧带附着情况也有所改善,无细胞骨水泥的恢复就是证明。这些临床前数据与对两名 XLH 患者的回顾性分析结果一致,显示布罗苏单抗治疗可改善口腔特征。总之,我们的数据表明,FGF23-mAb 治疗能极大地改善牙槽组织,预示着它在牙科异常临床治疗中的益处。
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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
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