摘要
X连锁显性低血磷性佝偻病/骨软化(X-linked hypophosphatemic rickets/osteomalacia,XLH)是由X染色体上内肽酶同源磷调节基因(phosphate regulating endopeptidase homolog X-linked,PHEX)突变导致的最为常见的遗传性低磷血症。XLH的传统治疗方法是补充活性维生素D和中性磷制剂。2018年,成纤维细胞生长因子23(fibroblast growth factors 23,FGF23)单克隆抗体布罗索尤单抗被批准用于治疗1岁以上儿童和成人XLH患者,疗效显著优于传统治疗。其他以FGF23信号通路为治疗靶向的药物,如FGF23/FGFR/αKlotho抑制剂、FGF23 c端片段、FGF23下游通路MAPK的抑制剂等尚在动物实验阶段,在PHEX基因失活性突变的小鼠模型(Hyp小鼠)中被证明可以纠正低磷血症并改善骨骼矿化,有望进一步成为XLH的新治疗手段。
X-linked hypophosphatemic rickets/osteomalacia(XLH)is caused by the mutation in gene encoding phosphate regulating endopeptidase homolog X-linked(PHEX),which is the most common type of hereditary hypophosphatemia.The traditional therapy,which consists of oral supplemental phosphate and active vitamin D,has been the only remedy for XLH.In 2018,burosumab,a kind of fibroblast growth factors 23(FGF23)monoclonal antibody,received approval for children older than 1 year old and adults with XLH.Its efficacy is significantly superior to traditional therapy.Other drugs targeting the FGF23 pathway,including FGF23/FGFR/αKlotho inhibitor,FGF23 c-tail,and inhibitor of FGF23 downstream pathway,have been proven to rectify hypophosphatemia and improve bone mineralization in the mouse model with PHEX inactivating mutation(Hyp mouse),indicating to be promising therapeutics for XLH.
作者
邓思琪
章振林
岳华
DENG Si-qi;ZHANG Zhen-lin;YUE Hua(Shanghai Clinical Research Center of Bone Disease,Department of Osteoporosis and Bone Diseases,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200233,China)
出处
《中华骨质疏松和骨矿盐疾病杂志》
CSCD
北大核心
2024年第2期161-167,共7页
Chinese Journal Of Osteoporosis And Bone Mineral Research
基金
国家自然科学基金(82270932,81974126,81770874)。
