Methodology for the international working group clinical practice guidelines on X-linked hypophosphatemia in children and adults

Dalal S. Ali, Divisions of Endocrinology and Metabolism, McMaster University, 223 3075 Hospital Gate, Oakville, ON, L6M 1M1, Canada.
Aliya A. Khan, Divisions of Endocrinology and Metabolism, McMaster University, 223 3075 Hospital Gate, Oakville, ON, L6M 1M1, Canada. aliya@mcmaster.ca.
Reza D. Mirza, Department of Health Research Methods, Evidence, and Impact at McMaster University, Hamilton, Canada.
Natasha M. Appelman-Dijkstra, Department of Internal Medicine, Division of Endocrinology, Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.
Maria Luisa Brandi, F.I.R.M.O. Onlus, Italian Foundation for the Research on Bone Diseases, Florence, Italy.
Thomas O. Carpenter, Departments of Pediatrics (Endocrinology), and Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA.
Catherine Chaussain, Department of Oral Medicine, Faculty of Dentistry, Inserm and APHP, Université Paris Cité, Paris, France.
Erik A. Imel, Department of Medicine and Pediatrics, Endocrinology, Indiana University School of Medicine, Indianapolis, IN, USA.
Suzanne M. de Beur, University of Virginia School of Medicine, Charlottesville, VA, USA.
Pablo Florenzano, Department of Endocrinology, School of Medicine Pontificia, Universidad Católica de Chile, Santiago, Chile.
Archibald Morrison, Citadel Oral and Facial Surgery, Halifax, Canada.
Hajar Abu Alrob, Department of Health Research Methods, Evidence, and Impact at McMaster University, Hamilton, Canada.
R Todd Alexander, Department of Pediatrics, Faculty of Medicine and Dentistry, The University of Alberta, Edmonton, AB, Canada.
Farah Alsarraf, Divisions of Endocrinology and Metabolism, McMaster University, 223 3075 Hospital Gate, Oakville, ON, L6M 1M1, Canada.
Signe Sparre Beck-Nielsen, Centre for Rare Diseases, Aarhus University Hospital, Aarhus, Denmark.
Martin Biosse-Duplan, Department of Oral Medicine, Faculty of Dentistry, Inserm and APHP, Université Paris Cité, Paris, France.
Martine Cohen-Solal, Department of Rheumatology and Reference Center for Rare Bone Diseases, Hopital Lariboisiere, Paris, France.
Rachel K. Crowley, Rare Disease Clinical Trial Network, University College Dublin, Dublin, Ireland.
Karel Dandurand, Université de Sherbrooke, Sherbrooke, QC, Canada.
Guido Filler, Department of Paediatrics, Western University, London, ON, Canada.
Seiji Fukumoto, Department of Medicine, Tamaki-Aozora Hospital, Tokushima, Japan.
Claudia Gagnon, Department of Medicine, Université Laval, Quebec City, Canada.
Paul Goodyer, Research Institute of the McGill University Health Centre, Montreal, Canada.
Corinna Grasemann, Department of Pediatrics, Division of Rare Diseases, Katholisches Klinikum Bochum and Ruhr-University Bochum, Bochum, Germany.
Chelsey Grimbly, Department of Pediatrics, Faculty of Medicine and Dentistry, The University of Alberta, Edmonton, AB, Canada.
Salma Hussein, Divisions of Endocrinology and Metabolism, McMaster University, 223 3075 Hospital Gate, Oakville, ON, L6M 1M1, Canada.
Muhammad K. Javaid, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Sarah Khan, Trillium Health Partners, University of Toronto, Toronto, ON, Canada.
Aneal Khan, M.A.G.I.C. Clinic (Metabolics and Genetics in Canada), Calgary, AB, Canada.
Anna Lehman, University of British Columbia, Adult Metabolic Diseases Clinic, Vancouver, BC, Canada.
Willem F. Lems, Department of Rheumatology, UMC, Amsterdam, the Netherlands.
E Michael Lewiecki, New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA.

Document Type

Journal Article

Publication Date

3-21-2025

Journal

Journal of bone and mineral metabolism

DOI

10.1007/s00774-025-01585-z

Abstract

The guideline panel, comprising international experts in X-linked hypophosphatemia (XLH), patient partners from the XLH patient population, and guideline methodologists, held 18 teleconferences between January 2023 and July 2024 to develop comprehensive guidelines for the diagnosis and management of XLH in children and adults. For a subset of our questions, we utilized the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, assessed the certainty of evidence and formulated GRADEd recommendations. For these questions, the panelists and methodologists collaboratively framed PICO (Population, Intervention, Control, and Outcomes) questions and conducted four systematic reviews assessing the impact of medical therapy-using either burosumab or phosphate and active vitamin D-on patient-important outcomes in the XLH population as well as the impact of medical intervention compared to no treatment. We assessed the risk of bias and transparently generated summary of findings tables using MAGICApp. The panel developed three GRADEd treatment recommendations for adults and two for children. Each GRADEd recommendation was linked to an underlying body of evidence, reflecting judgments on the certainty of evidence, recommendation strength, values, preferences, and considerations of costs, feasibility, acceptability, and equity. Due to the paucity of evidence, the panel developed very low-quality GRADEd recommendations on monitoring patients with XLH based on an expert clinical practice survey. Using a rigorous narrative literature review, the panel developed non-GRADEd recommendations including guidance for pregnant women, patients with dental complications, and other areas where evidence is limited. This article summarizes the methodology utilized for the development of both GRADEd and non-GRADEd recommendations for patients with XLH.

Department

Orthopaedic Surgery

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