. 2025 Apr 22;110(5):1205-1217.

doi: 10.1210/clinem/dgaf011.

Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Pediatric Patients With X-Linked Hypophosphatemia

Dalal S Ali¹, Reza D Mirza², Salma Hussein¹, Farah Alsarraf¹, R Todd Alexander³, Hajar Abu Alrob², Natasha M Appelman-Dijkstra⁴, Martin Biosse-Duplan^{5

6

7}, Maria Luisa Brandi⁸, Thomas O Carpenter⁹, Catherine Chaussain^{5

6}, Karel Dandurand¹⁰, Guido Filler¹¹, Pablo Florenzano¹², Seiji Fukumoto¹³, Corinna Grasemann¹⁴, Erik A Imel¹⁵, Suzanne M Jan de Beur¹⁶, Emmett Morgante¹⁷, Leanne M Ward¹⁸, Aliya A Khan¹, Gordon Guyatt^{2

19

20}

Affiliations

¹ Division of Endocrinology and Metabolism, McMaster University, Hamilton, ON, Canada L8S 4L8.
² Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada L8S 4L8.
³ Department of Pediatrics, Faculty of Medicine & Dentistry, The University of Alberta, Edmonton, AB, Canada T6G 2R3.
⁴ Department of Internal Medicine, Division of Endocrinology, Center for Bone Quality, Leiden University Medical Center, 2300 ZA Leiden, the Netherlands.
⁵ Department of Oral Medicine, Faculty of Dentistry, UMR 1333, Université Paris Cité, 75006 Paris, France.
⁶ Institut Imagine, INSERM 1163, 75015 Paris, France.
⁷ Department of Odontology, Bretonneau Hospital, APHP, 75006 Paris, France.
⁸ Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University and IRCCS, 20132 Milan, Italy.
⁹ Departments of Pediatrics (Endocrinology), and Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06520, USA.
¹⁰ Division of Internal Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
¹¹ Department of Paediatrics, Endocrinology Division, Western University, London, ON, Canada N6A 3K7.
¹² Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile, 8320165 Santiago, Región Metropolitana, Chile.
¹³ Department of Medicine, Tamaki-Aozora Hospital, 779-3125 Tokushima, Japan.
¹⁴ Department of Pediatrics, Division of Rare Diseases, Katholisches Klinikum Bochum and Ruhr-University Bochum, 44791 Bochum, Germany.
¹⁵ Department of Medicine and Pediatrics, Endocrinology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
¹⁶ Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
¹⁷ Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada N2L 3G1.
¹⁸ Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada K1H 8L1.
¹⁹ Department of Medicine, McMaster University, Hamilton, ON, Canada L8S 4L8.
²⁰ MAGIC Evidence Ecosystem Foundation [www.magicevidence.org], Oslo 0456, Norway.

PMID: 39787354
PMCID: PMC12012687
DOI: 10.1210/clinem/dgaf011

Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Pediatric Patients With X-Linked Hypophosphatemia

Dalal S Ali et al. J Clin Endocrinol Metab. 2025.

. 2025 Apr 22;110(5):1205-1217.

doi: 10.1210/clinem/dgaf011.

Authors

Affiliations

¹ Division of Endocrinology and Metabolism, McMaster University, Hamilton, ON, Canada L8S 4L8.
² Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada L8S 4L8.
³ Department of Pediatrics, Faculty of Medicine & Dentistry, The University of Alberta, Edmonton, AB, Canada T6G 2R3.
⁴ Department of Internal Medicine, Division of Endocrinology, Center for Bone Quality, Leiden University Medical Center, 2300 ZA Leiden, the Netherlands.
⁵ Department of Oral Medicine, Faculty of Dentistry, UMR 1333, Université Paris Cité, 75006 Paris, France.
⁶ Institut Imagine, INSERM 1163, 75015 Paris, France.
⁷ Department of Odontology, Bretonneau Hospital, APHP, 75006 Paris, France.
⁸ Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University and IRCCS, 20132 Milan, Italy.
⁹ Departments of Pediatrics (Endocrinology), and Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06520, USA.
¹⁰ Division of Internal Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada J1H 5N4.
¹¹ Department of Paediatrics, Endocrinology Division, Western University, London, ON, Canada N6A 3K7.
¹² Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile, 8320165 Santiago, Región Metropolitana, Chile.
¹³ Department of Medicine, Tamaki-Aozora Hospital, 779-3125 Tokushima, Japan.
¹⁴ Department of Pediatrics, Division of Rare Diseases, Katholisches Klinikum Bochum and Ruhr-University Bochum, 44791 Bochum, Germany.
¹⁵ Department of Medicine and Pediatrics, Endocrinology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
¹⁶ Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
¹⁷ Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada N2L 3G1.
¹⁸ Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada K1H 8L1.
¹⁹ Department of Medicine, McMaster University, Hamilton, ON, Canada L8S 4L8.
²⁰ MAGIC Evidence Ecosystem Foundation [www.magicevidence.org], Oslo 0456, Norway.

PMID: 39787354
PMCID: PMC12012687
DOI: 10.1210/clinem/dgaf011

Abstract

Objective: To examine the evidence addressing the management of X-linked hypophosphatemia (XLH) in children to inform treatment recommendations.

Methods: We searched Embase, MEDLINE, Web of Science, and Cochrane Central up to May 2023. Eligible studies included randomized controlled trials (RCTs) and observational studies of individuals younger than 18 years with clinically or genetically confirmed XLH. Manuscripts comparing burosumab to either no treatment or conventional therapy (phosphate and active vitamin D) or evaluating conventional therapy to no treatment were included. Two reviewers independently determined eligibility, extracted data, and assessed risk of bias (RoB). GRADE methodology was used to assess evidence certainty.

Results: We screened 4114 records and assessed 254 full texts. One RCT and one post hoc study proved eligible when comparing burosumab to conventional therapy or no treatment. The open-label RCT was at high RoB, with certainty of evidence ranging from moderate to very low. Burosumab, compared to conventional therapy, probably prevents lower limb deformity and improves physical health quality of life (QoL) (moderate certainty). Burosumab may increase height and enhance the burden of symptoms related to chronic hypophosphatemia (low certainty). Burosumab probably increases treatment-emergent adverse events (moderate certainty) and may increase dental abscesses (low certainty). One observational study assessing conventional therapy vs no treatment was at high RoB, providing very low certainty evidence regarding the impact of conventional therapy on final height.

Conclusion: Our review indicates that burosumab likely provides benefits to children by preventing lower limb deformity and improving physical health QoL while potentially increasing height. However, burosumab may also increase adverse events. Our review found limited evidence regarding the impact of conventional therapy compared to no treatment on final height. Further research is required to understand the long-term effect of medical therapy in children.

Keywords: burosumab; children XLH; conventional therapy; efficacy; patient-important outcomes; pediatric XLH.

PubMed Disclaimer

Figures

**Figure 1.**
PRISMA 2020 flow diagram for SR addressing the impact of burosumab vs conventional therapy.

**Figure 2.**
PRISMA 2020 flow diagram for SR addressing the impact of conventional therapy vs no treatment.

**Figure 3.**
Risk of bias assessment of SR comparing burosumab to conventional therapy (RCT) (17).

**Figure 4.**
Risk of bias assessment in the observational studies included in both systematic reviews (18, 19).

See this image and copyright information in PMC

References

1. Liu S, Tang W, Zhou J, et al. . Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol. 2006;17(5):1305‐1315. - PubMed
1. Hawley S, Shaw NJ, Delmestri A, et al. . Prevalence and mortality of individuals with X-linked hypophosphatemia: a United Kingdom real-world data analysis. J Clin Endocrinol Metab. 2020;105(3):e871‐e878. - PMC - PubMed
1. Che H, Roux C, Etcheto A, et al. . Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms. Eur J Endocrinol. 2016;174(3):325‐333. - PubMed
1. Biosse Duplan M, Coyac BR, Bardet C, et al. . Phosphate and vitamin D prevent periodontitis in X-linked hypophosphatemia. J Dent Res. 2017;96(4):388‐395. - PubMed
1. Page MJ, McKenzie JE, Bossuyt PM, et al. . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

Grants and funding

McMaster University

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Pediatric Patients With X-Linked Hypophosphatemia

Affiliations

Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Pediatric Patients With X-Linked Hypophosphatemia

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources