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

Aliya A. Khan, Division of Endocrinology and Metabolism, McMaster University, Hamilton, ON L8S 4L8, Canada.
Dalal S. Ali, Division of Endocrinology and Metabolism, McMaster University, Hamilton, ON L8S 4L8, Canada.
Natasha M. Appelman-Dijkstra, Department of Internal Medicine, Division of Endocrinology, Center for Bone Quality, Leiden University Medical Center, Leiden 2300 ZA, the Netherlands.
Thomas O. Carpenter, Departments of Pediatrics (Endocrinology), and Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06520, USA.
Catherine Chaussain, Department of Oral Medicine, Faculty of Dentistry, UMR 1333, Université Paris Cité, Paris 75006, France.
Erik A. Imel, Department of Medicine and Pediatrics, Endocrinology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Suzanne M. Jan de Beur, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
Pablo Florenzano, Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile, Santiago 8320165, Región Metropolitana, Chile.
Hajar Abu Alrob, Department of Health Research Methods, Evidence, and Impact at McMaster University, Hamilton, ON L8S 4L8, Canada.
Rana Aldabagh, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 2L3, Canada.
R Todd Alexander, Faculty of Medicine & Dentistry, The University of Alberta, Edmonton, AB T6G 2R3, Canada.
Farah Alsarraf, Division of Endocrinology and Metabolism, McMaster University, Hamilton, ON L8S 4L8, Canada.
Signe Sparre Beck-Nielsen, Centre for Rare Diseases, Aarhus University Hospital, Aarhus N 8200, Denmark.
Martin Biosse-Duplan, Department of Oral Medicine, Faculty of Dentistry, UMR 1333, Université Paris Cité, Paris 75006, France.
Martine Cohen-Solal, Department of Rheumatology and reference center for Rare Bone Diseases, hopital Lariboisiere, Paris 75006, France.
Rachel K. Crowley, Rare Disease Clinical Trial Network, University College Dublin, Dublin 4, D04 T6F4, Ireland.
Karel Dandurand, Division of Internal Medicine, Endocrinology Division, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Guido Filler, London Health Sciences Centre, Children's Hospital of Western Ontario, London, ON N6A 3K7, Canada.
Lisa Friedlander, Department of Oral Medicine, Faculty of Dentistry, UMR 1333, Université Paris Cité, Paris 75006, France.
Seiji Fukumoto, Department of Medicine, Tamaki-Aozora Hospital, Tokushima 779-3125, Japan.
Claudia Gagnon, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Centre, Québec, QC G1V 4G2, Canada.
Paul Goodyer, Research Institute of the McGill University Health Centre, Montreal, QC H3H 2L9, Canada.
Corinna Grasemann, Department of Pediatrics, Division of Rare Diseases, Katholisches Klinikum Bochum and Ruhr-University Bochum, 44791 Bochum, Germany.
Chelsey Grimbly, Department of Pediatrics, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Salma Hussein, Division of Endocrinology and Metabolism, McMaster University, Hamilton, ON L8S 4L8, Canada.
Muhammad K. Javaid, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7HE, UK.
Sarah Khan, Trillium Health Partners, University of Toronto, Toronto, ON L5M 2N1, Canada.
Aneal Khan, M.A.G.I.C. Clinic (Metabolics and Genetics in Canada), Calgary, AB T2E 7Z4, Canada.
Anna Lehman, Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Willem F. Lems, Department of Rheumatology, Amsterdam UMC, Amsterdam 1105 AZ, the Netherlands.
E Michael Lewiecki, New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM 87106, USA.
Ciara McDonnell, Department of Pediatric Endocrinology & Diabetes, Children's Health Ireland, Dublin D12 N512, Ireland.

Document Type

Journal Article

Publication Date

4-17-2025

Journal

The Journal of clinical endocrinology and metabolism

DOI

10.1210/clinem/dgaf170

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).

Department

Orthopaedic Surgery

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