X-Linked Hypophosphatemia Management in Adults: An International Working Group Clinical Practice Guideline

Aliya A Khan; Dalal S Ali; Natasha M Appelman-Dijkstra; Thomas O Carpenter; Catherine Chaussain; Erik A Imel; Suzanne M Jan de Beur; Pablo Florenzano; Hajar Abu Alrob; Rana Aldabagh; R Todd Alexander; Farah Alsarraf; Signe Sparre Beck-Nielsen; Martin Biosse-Duplan; Martine Cohen-Solal; Rachel K Crowley; Karel Dandurand; Guido Filler; Lisa Friedlander; Seiji Fukumoto; Claudia Gagnon; Paul Goodyer; Corinna Grasemann; Chelsey Grimbly; Salma Hussein; Muhammad K Javaid; Sarah Khan; Aneal Khan; Anna Lehman; Willem F Lems; E Michael Lewiecki; Ciara McDonnell; Reza D Mirza; Emmett Morgante; Archibald Morrison; Anthony A Portale; Yumie Rhee; Eric T Rush; Heide Siggelkow; Sotirios Tetradis; Laura Tosi; Leanne M Ward; Gordon Guyatt; Maria Luisa Brandi

doi:10.1210/clinem/dgaf170

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X-Linked Hypophosphatemia Management in Adults: An International Working Group Clinical Practice Guideline

Authors: Aliya A Khan ; Dalal S Ali ; Natasha M Appelman-Dijkstra ; Thomas O Carpenter ; Catherine Chaussain ; Erik A Imel ; Suzanne M Jan de Beur ; Pablo Florenzano ; Hajar Abu Alrob ; Rana Aldabagh ; R Todd Alexander ; Farah Alsarraf ; Signe Sparre Beck-Nielsen ; Martin Biosse-Duplan ; Martine Cohen-Solal ; Rachel K Crowley ; Karel Dandurand ; Guido Filler ; Lisa Friedlander ; Seiji Fukumoto ; Claudia Gagnon ; Paul Goodyer ; Corinna Grasemann ; Chelsey Grimbly ; Salma Hussein ; Muhammad K Javaid ; Sarah Khan ; Aneal Khan ; Anna Lehman ; Willem F Lems ; E Michael Lewiecki ; Ciara McDonnell ; Reza D Mirza ; Emmett Morgante ; Archibald Morrison ; Anthony A Portale ; Yumie Rhee ; Eric T Rush ; Heide Siggelkow ; Sotirios Tetradis ; Laura Tosi ; Leanne M Ward ; Gordon Guyatt ; Maria Luisa Brandi

Citation: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol.110(8) : 2353-2370, 2025-07

Journal Title: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

ISSN: 0021-972X

Issue Date: 2025-07

MeSH: Adult ; Antibodies, Monoclonal, Humanized* / therapeutic use ; Disease Management ; Familial Hypophosphatemic Rickets* / diagnosis ; Familial Hypophosphatemic Rickets* / drug therapy ; Familial Hypophosphatemic Rickets* / genetics ; Familial Hypophosphatemic Rickets* / therapy ; Fibroblast Growth Factor-23 ; Humans ; PHEX Phosphate Regulating Neutral Endopeptidase / genetics

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

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).