{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:19:00Z","timestamp":1792887540733,"version":"4.5.0"},"reference-count":24,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013220","name":"Ultragenyx Pharmaceutical Inc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Younger age at treatment onset with conventional therapy (phosphate salts and active vitamin D; Pi\/D) is associated with improved growth and skeletal outcomes in children with X-linked hypophosphatemia (XLH). The effect of age on burosumab efficacy and safety in XLH is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This work aimed to explore the efficacy and safety of burosumab vs Pi\/D in younger (&amp;lt;\u20055 years) and older (5-12 years) children with XLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This post hoc analysis of a 64-week, open-label, randomized controlled study took place at 16 academic centers. Sixty-one children aged 1 to 12 years with XLH (younger, n\u2005=\u200526; older, n\u2005=\u200535) participated. Children received burosumab starting at 0.8 mg\/kg every 2 weeks (younger, n\u2005=\u200514; older, n\u2005=\u200515) or continued Pi\/D individually titrated per recommended guidelines (younger, n\u2005=\u200512; older, n\u2005=\u200520). The main outcome measure included the least squares means difference (LSMD) in Radiographic Global Impression of Change (RGI-C) rickets total score from baseline to week 64.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The LSMD in outcomes through 64 weeks on burosumab vs conventional therapy by age group were as follows: RGI-C rickets total score (younger, +0.90; older, +1.07), total Rickets Severity Score (younger, \u22120.86; older, \u22121.44), RGI-C lower limb deformity score (younger, +1.02; older, +0.91), recumbent length or standing height Z-score (younger, +0.20; older, +0.09), and serum alkaline phosphatase (ALP) (younger, \u221231.15% of upper normal limit [ULN]; older, \u221252.11% of ULN). On burosumab, dental abscesses were not reported in younger children but were in 53% of older children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Burosumab appears to improve outcomes both in younger and older children with XLH, including rickets, lower limb deformities, growth, and ALP, compared with Pi\/D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgac296","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T15:59:42Z","timestamp":1652111982000},"page":"e3241-e3253","source":"Crossref","is-referenced-by-count":81,"title":["Effect of Burosumab Compared With Conventional Therapy on Younger vs Older Children With X-linked Hypophosphatemia"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1557-9185","authenticated-orcid":false,"given":"Leanne M","family":"Ward","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Ottawa , Ottawa, Ontario K1H 8L1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis H","family":"Glorieux","sequence":"additional","affiliation":[{"name":"Shriners Hospitals for Children, Canada, McGill University , Montreal, Quebec H4A OA9 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P","family":"Whyte","sequence":"additional","affiliation":[{"name":"Shriners Hospitals for Children St Louis , St Louis, Missouri 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig F","family":"Munns","sequence":"additional","affiliation":[{"name":"Child Health Research Centre, The University of Queensland , Brisbane, Queensland 4072 , Australia"},{"name":"Department of Endocrinology and Diabetes, Queensland Children\u2019s Hospital , Brisbane, Queensland 4101 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony A","family":"Portale","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Francisco , San Francisco, California 94143 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"H\u00f6gler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Johannes Kepler University Linz , Linz 4040 , Austria"},{"name":"Institute of Metabolism and Systems Research, University of Birmingham , Birmingham, B15 2TT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill H","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Endocrinology and Diabetes, Vanderbilt University School of Medicine, Vanderbilt University , 680-8570 Nashville, Tennessee, 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0302-3852","authenticated-orcid":false,"given":"Gary S","family":"Gottesman","sequence":"additional","affiliation":[{"name":"Shriners Hospitals for Children St Louis , St Louis, Missouri 63110 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja","family":"Padidela","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology, Royal Manchester Children\u2019s Hospital , Manchester M13 9WL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3803-4500","authenticated-orcid":false,"given":"Noriyuki","family":"Namba","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Osaka Hospital , Japan"},{"name":"Community Healthcare Organization"},{"name":"Osaka University Graduate School of Medicine , Osaka 553-0003 , Japan"},{"name":"Division of Pediatrics and Perinatology, Tottori University Faculty of Medicine , Yonago , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Il","family":"Cheong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul National University Children\u2019s Hospital , Seoul 14068 , South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology and Center for Molecular Medicine, Karolinska Institutet , Stockholm 17177 , Sweden"},{"name":"School of Medical Sciences, Department of Pediatrics, \u00d6rebro University and University Hospital , \u00d6rebro S-703 62 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7745-5359","authenticated-orcid":false,"given":"Meng","family":"Mao","sequence":"additional","affiliation":[{"name":"Ultragenyx Pharmaceutical Inc , Novato, California 94949 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Chen","sequence":"additional","affiliation":[{"name":"Ultragenyx Pharmaceutical Inc , Novato, California 94949 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Skrinar","sequence":"additional","affiliation":[{"name":"Ultragenyx Pharmaceutical Inc , Novato, California 94949 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Scott","family":"Roberts","sequence":"additional","affiliation":[{"name":"Ultragenyx Pharmaceutical Inc , Novato, California 94949 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7284-3467","authenticated-orcid":false,"given":"Erik A","family":"Imel","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Pediatrics, Indiana University School of Medicine , Indianapolis, Indianapolis 46202 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"2022071417213172800_CIT0001","doi-asserted-by":"crossref","first-page":"17101","DOI":"10.1038\/nrdp.2017.101","article-title":"Rickets","volume":"3","author":"Carpenter","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"2022071417213172800_CIT0002","first-page":"17","article-title":"FGF23 and associated disorders of phosphate wasting","volume":"17","author":"Gohil","year":"2019","journal-title":"Pediatr Endocrinol Rev"},{"issue":"10","key":"2022071417213172800_CIT0003","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1210\/clinem\/dgaa495","article-title":"Growth curves for children with X-linked hypophosphatemia","volume":"105","author":"Mao","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2022071417213172800_CIT0004","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0031-3955(05)70485-5","article-title":"New perspectives on the biology and treatment of X-linked hypophosphatemic rickets","volume":"44","author":"Carpenter","year":"1997","journal-title":"Pediatr Clin North Am"},{"issue":"7","key":"2022071417213172800_CIT0005","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1002\/jbmr.340","article-title":"A clinician\u2019s guide to X-linked hypophosphatemia","volume":"26","author":"Carpenter","year":"2011","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2022071417213172800_CIT0006","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/EC-13-0103","article-title":"Therapeutic management of hypophosphatemic rickets from infancy to adulthood","volume":"3","author":"Linglart","year":"2014","journal-title":"Endocr Connect"},{"issue":"10","key":"2022071417213172800_CIT0007","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1210\/JC.2015-2199","article-title":"Conventional therapy in adults with X-linked hypophosphatemia: effects on enthesopathy and dental disease","volume":"100","author":"Connor","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2022071417213172800_CIT0008","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13023-019-1014-8","article-title":"FGF23 and its role in X-linked hypophosphatemia-related morbidity","volume":"14","author":"Beck-Nielsen","year":"2019","journal-title":"Orphanet J Rare Dis"},{"issue":"10189","key":"2022071417213172800_CIT0009","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1016\/S0140-6736(19)30654-3","article-title":"Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial","volume":"393","author":"Imel","year":"2019","journal-title":"Lancet"},{"issue":"8","key":"2022071417213172800_CIT0010","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1210\/jc.2003-030036","article-title":"Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets","volume":"88","author":"M\u00e4kitie","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2022071417213172800_CIT0011","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00467-011-2046-z","article-title":"Growth in PHEX-associated X-linked hypophosphatemic rickets: the importance of early treatment","volume":"27","author":"Quinlan","year":"2012","journal-title":"Pediatr Nephrol"},{"issue":"26","key":"2022071417213172800_CIT0012","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1056\/NEJM199112263252604","article-title":"Effects of therapy in X-linked hypophosphatemic rickets","volume":"325","author":"Verge","year":"1991","journal-title":"N Engl J Med"},{"issue":"5","key":"2022071417213172800_CIT0013","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1002\/jbmr.3377","article-title":"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","volume":"33","author":"Whyte","year":"2018","journal-title":"J Bone Miner Res"},{"key":"2022071417213172800_CIT0014","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.bone.2019.02.010","article-title":"Rickets severity predicts clinical outcomes in children with X-linked hypophosphatemia: utility of the radiographic Rickets Severity Score","volume":"122","author":"Thacher","year":"2019","journal-title":"Bone"},{"issue":"9","key":"2022071417213172800_CIT0015","doi-asserted-by":"crossref","first-page":"e72816","DOI":"10.1371\/journal.pone.0072816","article-title":"FGF-23 regulates CYP27B1 transcription in the kidney and in extra-renal tissues","volume":"8","author":"Chanakul","year":"2013","journal-title":"PLoS One"},{"issue":"3","key":"2022071417213172800_CIT0016","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1359\/JBMR.0301264","article-title":"FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis","volume":"19","author":"Shimada","year":"2004","journal-title":"J Bone Miner Res"},{"issue":"21","key":"2022071417213172800_CIT0017","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1056\/NEJMoa1714641","article-title":"Burosumab therapy in children with X-linked hypophosphatemia","volume":"378","author":"Carpenter","year":"2018","journal-title":"N Engl J Med"},{"issue":"3","key":"2022071417213172800_CIT0018","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S2213-8587(18)30338-3","article-title":"Efficacy and safety of burosumab in children aged 1-4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial","volume":"7","author":"Whyte","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"8","key":"2022071417213172800_CIT0019","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1002\/jbmr.3475","article-title":"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","volume":"33","author":"Insogna","year":"2018","journal-title":"J Bone Miner Res"},{"issue":"12","key":"2022071417213172800_CIT0020","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1002\/jbmr.3843","article-title":"Burosumab improved histomorphometric measures of osteomalacia in adults with X-linked hypophosphatemia: a phase 3, single-arm, international trial","volume":"34","author":"Insogna","year":"2019","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2022071417213172800_CIT0021","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/prd.12029","article-title":"Extracellular matrix mineralization in periodontal tissues: noncollagenous matrix proteins, enzymes, and relationship to hypophosphatasia and X-linked hypophosphatemia","volume":"63","author":"McKee","year":"2013","journal-title":"Periodontol 2000"},{"key":"2022071417213172800_CIT0022","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/03008207.2017.1417989","article-title":"Impaired mineral quality in dentin in X-linked hypophosphatemia","volume":"59","author":"Coyac","year":"2018","journal-title":"Connect Tissue Res"},{"key":"2022071417213172800_CIT0023","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3109\/03008207.2014.923864","article-title":"Abnormal osteopontin and matrix extracellular phosphoglycoprotein localization, and odontoblast differentiation, in X-linked hypophosphatemic teeth","volume":"55","author":"Salmon","year":"2014","journal-title":"Connect Tissue Res"},{"issue":"12","key":"2022071417213172800_CIT0024","doi-asserted-by":"crossref","first-page":"bvaa151","DOI":"10.1210\/jendso\/bvaa151","article-title":"X-linked hypophosphatemia: a new era in management","volume":"4","author":"Dahir","year":"2020","journal-title":"J Endocr Soc"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgac296\/43845657\/dgac296.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/107\/8\/e3241\/44886195\/dgac296.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/107\/8\/e3241\/44886195\/dgac296.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T13:22:17Z","timestamp":1657804937000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/107\/8\/e3241\/6582860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,9]]},"references-count":24,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,5,9]]},"published-print":{"date-parts":[[2022,7,14]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgac296","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,8,1]]},"published":{"date-parts":[[2022,5,9]]}}}