Effects of Burosumab Treatment on Mineral Metabolism in Children and Adolescents With X-linked Hypophosphatemia.

Autor:	Ewert A; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover 30625, Germany., Rehberg M; Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne 50937, Germany., Schlingmann KP; Department of General Pediatrics, Pediatric Nephrology, University Children's Hospital, Münster 48149, Germany., Hiort O; Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Lübeck, Lübeck 23562, Germany., John-Kroegel U; University Children's Hospital, Jena 07743, Germany., Metzing O; University Children's Hospital, Jena 07743, Germany., Wühl E; Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg 69120, Germany., Schaefer F; Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg 69120, Germany., Kemper MJ; Asklepios Children's Hospital Hamburg-Heidberg, Hamburg-Heidberg 22417, Germany., Derichs U; University Children's Hospital, Mainz 55131, Germany., Richter-Unruh A; University Children's Hospital Bochum, Bochum 44892, Germany., Patzer L; St. Elisabeth and St. Barbara Children's Hospital, Halle/Saale 06110, Germany., Albers N; Christliches Kinderhospital Osnabrück, Osnabrück 49074, Germany., Dunstheimer D; University Children's Hospital Augsburg, Augsburg 86156, Germany., Haberland H; Children's Hospital, Sana Klinikum Lichtenberg, Berlin Lichtenberg 10365, Germany., Heger S; Kinderkrankenhaus auf der Bult, Hannover 30173, Germany., Schröder C; University Children's Hospital Greifswald, Greifswald 17475, Germany., Jorch N; University Children's Hospital, Evangelisches Klinikum Bethel, Bielefeld 33617, Germany., Schmid E; Clinic for Pediatric Nephrology Hirschaid, Hirschaid 96114, Germany., Staude H; University Children's Hospital Rostock, Rostock 18057, Germany., Weitz M; Department of General Pediatrics and Hematology/Oncology, University Children's Hospital, University Hospital Tübingen, Tübingen 72076, Germany., Freiberg C; Department of Pediatrics and Adolescent Medicine, University Medical Center Göttingen, Göttingen 37075, Germany., Leifheit-Nestler M; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover 30625, Germany., Zivicnjak M; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover 30625, Germany., Schnabel D; Center for Chronically Sick Children, Pediatric Endocrinology, University Medicine, Charité, Berlin 13353, Germany., Haffner D; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover 30625, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2023 Sep 18; Vol. 108 (10), pp. e998-e1006.
DOI:	10.1210/clinem/dgad223
Abstrakt:	Context: Burosumab has been approved for the treatment of children and adults with X-linked hypophosphatemia (XLH). Real-world data and evidence for its efficacy in adolescents are lacking. Objective: To assess the effects of 12 months of burosumab treatment on mineral metabolism in children (aged <12 years) and adolescents (aged 12-18 years) with XLH. Design: Prospective national registry. Setting: Hospital clinics. Patients: A total of 93 patients with XLH (65 children, 28 adolescents). Main Outcome Measures: Z scores for serum phosphate, alkaline phosphatase (ALP), and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR) at 12 months. Results: At baseline, patients showed hypophosphatemia (-4.4 SD), reduced TmP/GFR (-6.5 SD), and elevated ALP (2.7 SD, each P < .001 vs healthy children) irrespective of age, suggesting active rickets despite prior therapy with oral phosphate and active vitamin D in 88% of patients. Burosumab treatment resulted in comparable increases in serum phosphate and TmP/GFR in children and adolescents with XLH and a steady decline in serum ALP (each P < .001 vs baseline). At 12 months, serum phosphate, TmP/GFR, and ALP levels were within the age-related normal range in approximately 42%, 27%, and 80% of patients in both groups, respectively, with a lower, weight-based final burosumab dose in adolescents compared with children (0.72 vs 1.06 mg/kg, P < .01). Conclusions: In this real-world setting, 12 months of burosumab treatment was equally effective in normalizing serum ALP in adolescents and children, despite persistent mild hypophosphatemia in one-half of patients, suggesting that complete normalization of serum phosphate is not mandatory for substantial improvement of rickets in these patients. Adolescents appear to require lower weight-based burosumab dosage than children. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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