Document Type

Article

Publication Date

7-15-2025

Identifier

DOI: 10.1210/clinem/dgaf170; PMCID: PMC12261105

Abstract

PURPOSE: An international working group (IWG) consisting of experts in X-linked hypophosphatemia (XLH) developed global guidelines providing a comprehensive, evidence-based approach to XLH diagnosis, management, and monitoring.

METHODS: The IWG, consisting of 43 members as well as methodologists and a patient partner, conducted 2 systematic reviews (SRs) and narrative reviews to address key areas. The SRs addressed the impact of burosumab compared to conventional therapy (phosphate and active vitamin D) or no therapy on patient-important outcomes in adults. They also evaluated conventional therapy compared to no therapy. GRADE methodology was applied to evaluate the certainty of evidence. Non-GRADED recommendations were made in the presence of insufficient evidence to conduct SRs. These guidelines have been reviewed and endorsed by several medical and patient societies and organizations.

RESULTS: The diagnosis of XLH is based on integrating clinical evaluation, laboratory findings confirming renal phosphate wasting (following exclusion of conditions mimicking XLH), and skeletal imaging. Fibroblast growth factor 23 measurement and DNA analysis are of value in the diagnosis, if available. Pathogenic or likely pathogenic variants in the PHEX gene are confirmatory but not necessary for the diagnosis. Management requires a multidisciplinary team knowledgeable and experienced in XLH. Effective medical therapy with burosumab can improve fracture and pseudofracture healing.

MAIN CONCLUSION: In adults with XLH and fractures or pseudofractures, burosumab is recommended over no therapy (strong recommendation, GRADEd). Additionally, burosumab is suggested as the preferred treatment compared to conventional therapy (conditional recommendation, GRADEd) in the absence of fractures or pseudofractures. If burosumab is not available, symptomatic adults should be treated with conventional therapy (Non-GRADEd recommendation).

Journal Title

The Journal of clinical endocrinology and metabolism

Volume

110

Issue

8

First Page

2353

Last Page

2370

MeSH Keywords

Humans; Familial Hypophosphatemic Rickets; Adult; Fibroblast Growth Factor-23; Antibodies, Monoclonal, Humanized; PHEX Phosphate Regulating Neutral Endopeptidase; Disease Management

PubMed ID

40243526

Keywords

X-linked hypophosphatemia (XLH); adult XLH; clinical practice guidelines; consensus

Comments

Grants and funding

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited.

Publisher's Link: https://academic.oup.com/jcem/article-lookup/doi/10.1210/clinem/dgaf170

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