Burosumab for Pediatric X-Linked Hypophosphatemia

Overview

Journal Curr Osteoporos Rep

Publisher Current Science

Specialties Endocrinology
Orthopedics

Date 2021 May 10

PMID 33970403

Citations 15

Authors

Erik A Imel

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: X-Linked hypophosphatemia (XLH) is the most common genetic cause of rickets. This review describes advances in the management of XLH using burosumab which was FDA approved for treating children with XLH in 2018.

Recent Findings: Elevated FGF23 in XLH leads to systemic hypophosphatemia and several musculoskeletal manifestations, including rachitic bone deformities, impaired growth, dental abscesses, insufficiency fractures, osteoarthritis, and enthesopathy, with lifelong consequences for physical function and quality of life. Burosumab treatment has demonstrated clinical improvement of rickets and growth in children, including during a randomized controlled trial compared with conventional therapy. Burosumab also improved pseudofracture healing in adults. Burosumab led to greater improvement in rickets and growth than conventional therapy. However, many questions remain regarding the impact of burosumab on several outcomes, including final height, nephrocalcinosis, dental disease, enthesopathy, and surgical interventions.

Citing Articles

Calcium-phosphate metabolism - selected disorders in children.

Jakubowska-Pietkiewicz E Pediatr Endocrinol Diabetes Metab. 2025; 30(4):169-173.

PMID: 39963053 PMC: 11809548. DOI: 10.5114/pedm.2024.146682.

A Case of Hypophosphatasia Started Enzyme Replacement Therapy Since Babyhood Stage.

Akitomo T, Niizato N, Kaneki A, Ogawa M, Nishimura T, Kametani M Children (Basel). 2025; 12(1).

PMID: 39857892 PMC: 11764115. DOI: 10.3390/children12010061.

Use of Whole-Exome Sequencing and Pedigree Analysis to Identify X-linked Hypophosphatemia in Saudi Arabian Families.

Al-Hamed M, Bakhamis S, Abdelfattah S, Alsagheir A J Endocr Soc. 2024; 9(1):bvae203.

PMID: 39659542 PMC: 11631126. DOI: 10.1210/jendso/bvae203.

Real-World Clinical and Healthcare Resource Burden Among Burosumab-Naïve Patients With Familial Hypophosphatemia.

Imel E, Li Z, Heerssen H, Princic N, Schwartz H, Zhao Y J Endocr Soc. 2024; 8(12):bvae185.

PMID: 39539413 PMC: 11558453. DOI: 10.1210/jendso/bvae185.

Inherited phosphate and pyrophosphate disorders: New insights and novel therapies changing the oral health landscape.

Foster B, Boyce A, Millan J, Kramer K, Ferreira C, Somerman M J Am Dent Assoc. 2024; 155(11):912-925.

PMID: 39127957 PMC: 11540754. DOI: 10.1016/j.adaj.2024.05.016.

References

Whyte M, Fujita K, Moseley S, Thompson D, McAlister W . Validation of a Novel Scoring System for Changes in Skeletal Manifestations of Hypophosphatasia in Newborns, Infants, and Children: The Radiographic Global Impression of Change Scale. J Bone Miner Res. 2018; 33(5):868-874. DOI: 10.1002/jbmr.3377. View

Skrinar A, Dvorak-Ewell M, Evins A, Macica C, Linglart A, Imel E . The Lifelong Impact of X-Linked Hypophosphatemia: Results From a Burden of Disease Survey. J Endocr Soc. 2019; 3(7):1321-1334. PMC: 6595532. DOI: 10.1210/js.2018-00365. View

Chesher D, Oddy M, Darbar U, Sayal P, Casey A, Ryan A . Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations. J Inherit Metab Dis. 2018; 41(5):865-876. PMC: 6133187. DOI: 10.1007/s10545-018-0147-6. View

Larsson T, Marsell R, Schipani E, Ohlsson C, Ljunggren O, Tenenhouse H . Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis. Endocrinology. 2004; 145(7):3087-94. DOI: 10.1210/en.2003-1768. View

Imel E, Zhang X, Ruppe M, Weber T, Klausner M, Ito T . Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. J Clin Endocrinol Metab. 2015; 100(7):2565-73. PMC: 4495171. DOI: 10.1210/jc.2015-1551. View

Gordon R, Levine M . Burosumab treatment of children with X-linked hypophosphataemic rickets. Lancet. 2019; 393(10189):2364-2366. DOI: 10.1016/S0140-6736(19)31054-2. View

Tiosano D, Hochberg Z . Hypophosphatemia: the common denominator of all rickets. J Bone Miner Metab. 2009; 27(4):392-401. DOI: 10.1007/s00774-009-0079-1. View

Thacher T, Fischer P, Pettifor J, Lawson J, Manaster B, Reading J . Radiographic scoring method for the assessment of the severity of nutritional rickets. J Trop Pediatr. 2000; 46(3):132-9. DOI: 10.1093/tropej/46.3.132. View

Demay M, Sabbagh Y, Carpenter T . Calcium and vitamin D: what is known about the effects on growing bone. Pediatrics. 2007; 119 Suppl 2:S141-4. DOI: 10.1542/peds.2006-2023F. View

10.

DeLacey S, Liu Z, Broyles A, El-Azab S, Guandique C, James B . Hyperparathyroidism and parathyroidectomy in X-linked hypophosphatemia patients. Bone. 2019; 127:386-392. PMC: 6836672. DOI: 10.1016/j.bone.2019.06.025. View

11.

Carpenter T, Insogna K, Zhang J, Ellis B, Nieman S, Simpson C . Circulating levels of soluble klotho and FGF23 in X-linked hypophosphatemia: circadian variance, effects of treatment, and relationship to parathyroid status. J Clin Endocrinol Metab. 2010; 95(11):E352-7. PMC: 2968736. DOI: 10.1210/jc.2010-0589. View

12.

Makitie O, Doria A, Kooh S, Cole W, Daneman A, Sochett E . Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 2003; 88(8):3591-7. DOI: 10.1210/jc.2003-030036. View

13.

Aono Y, Hasegawa H, Yamazaki Y, Shimada T, Fujita T, Yamashita T . Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice. J Bone Miner Res. 2010; 26(4):803-10. DOI: 10.1002/jbmr.275. View

14.

Imel E, DiMeglio L, Hui S, Carpenter T, Econs M . Treatment of X-linked hypophosphatemia with calcitriol and phosphate increases circulating fibroblast growth factor 23 concentrations. J Clin Endocrinol Metab. 2010; 95(4):1846-50. PMC: 2853995. DOI: 10.1210/jc.2009-1671. View

15.

Imel E, Glorieux F, Whyte M, Munns C, Ward L, Nilsson O . Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019; 393(10189):2416-2427. PMC: 7179969. DOI: 10.1016/S0140-6736(19)30654-3. View

16.

Insogna K, Briot K, Imel E, Kamenicky P, Ruppe M, Portale A . A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. J Bone Miner Res. 2018; 33(8):1383-1393. DOI: 10.1002/jbmr.3475. View

17.

Zhang H, Chavez M, Kolli T, Tan M, Fong H, Chu E . Dentoalveolar Defects in the Mouse Model of X-linked Hypophosphatemia. J Dent Res. 2020; 99(4):419-428. PMC: 7088204. DOI: 10.1177/0022034520901719. View

18.

Sabbagh Y, Jones A, Tenenhouse H . PHEXdb, a locus-specific database for mutations causing X-linked hypophosphatemia. Hum Mutat. 2000; 16(1):1-6. DOI: 10.1002/1098-1004(200007)16:1<1::AID-HUMU1>3.0.CO;2-J. View

19.

Polisson R, Martinez S, Khoury M, Harrell R, Lyles K, Friedman N . Calcification of entheses associated with X-linked hypophosphatemic osteomalacia. N Engl J Med. 1985; 313(1):1-6. DOI: 10.1056/NEJM198507043130101. View

20.

Liang G, Katz L, Insogna K, Carpenter T, Macica C . Survey of the enthesopathy of X-linked hypophosphatemia and its characterization in Hyp mice. Calcif Tissue Int. 2009; 85(3):235-46. PMC: 2988401. DOI: 10.1007/s00223-009-9270-6. View