Department of Medicine Section of Endocrinology, Yale School of Medicine, PO Box 802080, New Haven, CT, 06520, USA.
Calcif Tissue Int. 2021 Jan;108(1):143-157. doi: 10.1007/s00223-020-00705-3. Epub 2020 Jun 5.
FGF23 is a hormone produced by osteocytes in response to an elevation in the concentration of extracellular phosphate. Excess production of FGF23 by bone cells, or rarely by tumors, is the hormonal basis for several musculoskeletal syndromes characterized by hypophosphatemia due to renal phosphate wasting. FGF23-dependent chronic hypophosphatemia causes rickets and osteomalacia, as well as other skeletal complications. Genetic disorders of FGF23-mediated hypophosphatemia include X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), fibrous dysplasia of bone, McCune-Albright syndrome, and epidermal nevus syndrome (ENS), also known as cutaneous skeletal hypophosphatemia syndrome (CSHS). The principle acquired form of FGF23-mediated hypophosphatemia is tumor-induced osteomalacia (TIO). This review summarizes current knowledge about the pathophysiology and clinical presentation of the most common FGF23-mediated conditions, with a focus on new treatment modalities. For many decades, calcitriol and phosphate supplements were the mainstay of therapy. Recently, burosumab, a monoclonal blocking antibody to FGF23, has been approved for treatment of XLH in children and adults, and an active comparator trial in children has shown good efficacy and safety for this drug. The remainder of FGF23-mediated hypophosphatemic disorders continue to be treated with phosphate and calcitriol, although ongoing trials with burosumab for treatment of tumor-induced osteomalacia show early promise. Burosumab may be an effective treatment for the remainder of FGF23-mediated disorders, but clinical trials to support that possibility are at present not available.
成纤维细胞生长因子 23（FGF23）是一种由骨细胞在细胞外磷酸盐浓度升高时产生的激素。骨细胞（或罕见的肿瘤）过度产生 FGF23 是几种肌肉骨骼综合征的激素基础，这些综合征的特征是由于肾脏磷酸盐丢失而导致低磷酸盐血症。FGF23 依赖性慢性低磷酸盐血症可引起佝偻病和骨软化症以及其他骨骼并发症。FGF23 介导的低磷酸盐血症的遗传疾病包括 X 连锁低磷酸盐血症（XLH）、常染色体显性低磷酸盐性佝偻病（ADHR）、常染色体隐性低磷酸盐性佝偻病（ARHR）、骨纤维发育不良、McCune-Albright 综合征和表皮痣综合征（ENS），也称为皮肤骨骼低磷酸盐血症综合征（CSHS）。FGF23 介导的低磷酸盐血症的主要获得形式是肿瘤诱导性骨软化症（TIO）。本文综述了目前关于最常见的 FGF23 介导的疾病的病理生理学和临床表现的知识，重点介绍了新的治疗方式。几十年来，骨化三醇和磷酸盐补充剂一直是治疗的主要方法。最近，一种针对 FGF23 的单克隆阻断抗体布罗索尤单抗已被批准用于儿童和成人 XLH 的治疗，一项针对儿童的活性对照试验表明该药具有良好的疗效和安全性。其余的 FGF23 介导的低磷酸盐血症疾病仍继续用磷酸盐和骨化三醇治疗，尽管布罗索尤单抗治疗肿瘤诱导性骨软化症的试验正在进行中，早期结果令人鼓舞。布罗索尤单抗可能是治疗其余 FGF23 介导的疾病的有效方法，但目前尚无支持这种可能性的临床试验。
