Interdisciplinary management of FGF23-related phosphate wasting syndromes: a Consensus Statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia

Nat Rev Endocrinol. 2022 Jun;18(6):366-384. doi: 10.1038/s41574-022-00662-x. Epub 2022 Apr 28.

Abstract

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Familial Hypophosphatemic Rickets* / diagnosis
  • Familial Hypophosphatemic Rickets* / drug therapy
  • Familial Hypophosphatemic Rickets* / genetics
  • Familial Hypophosphatemic Rickets* / metabolism
  • Fibroblast Growth Factor-23* / metabolism
  • Humans
  • Osteoarthritis* / diagnosis
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / genetics
  • Osteoarthritis* / metabolism
  • Quality of Life
  • Wasting Syndrome* / diagnosis
  • Wasting Syndrome* / drug therapy
  • Wasting Syndrome* / genetics
  • Wasting Syndrome* / metabolism

Substances

  • Fibroblast Growth Factor-23