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.

FGF23 是一种由骨细胞响应细胞外磷酸盐浓度升高而产生的激素。骨细胞或很少由肿瘤产生的 FGF23 过量产生是几种肌肉骨骼综合征的激素基础，其特征是由于肾磷酸盐消耗导致的低磷血症。FGF23 依赖性慢性低磷血症会导致佝偻病和骨软化症，以及其他骨骼并发症。FGF23 介导的低磷血症的遗传疾病包括 X 连锁低磷血症 (XLH)、常染色体显性低磷性佝偻病 (ADHR)、常染色体隐性低磷性佝偻病 (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血症综合征 (CSHS)。FGF23 介导的低磷血症的主要获得性形式是肿瘤诱导的骨软化症 (TIO)。这篇综述总结了目前关于最常见 FGF23 介导疾病的病理生理学和临床表现的知识，重点关注新的治疗方式。几十年来，骨化三醇和磷酸盐补充剂是治疗的主要支柱。最近，一种针对 FGF23 的单克隆阻断抗体 burosumab 已被批准用于治疗儿童和成人的 XLH，并且在儿童中进行的积极比较试验表明该药物具有良好的疗效和安全性。其余的 FGF23 介导的低磷血症继续用磷酸盐和骨化三醇治疗，尽管正在进行的 burosumab 治疗肿瘤诱导的骨软化症的试验显示出早期的希望。