{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:56:27Z","timestamp":1780059387763,"version":"3.54.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>In recent years, new therapies for the treatment of rare pediatric bone disorders have emerged, guided by an increasing understanding of the genetic and molecular etiology of these diseases. Herein, we review three such disorders, impacted by debilitating deficits in bone mineralization or cartilage ossification, as well as the novel disease-modifying drugs that are now available to treat these conditions. Specifically, we discuss asfotase alfa, burosumab-twza, and vosoritide, for the treatment of hypophosphatasia, X-linked hypophosphatemia and achondroplasia, respectively. For each skeletal disorder, an overview of the clinical phenotype and natural history of disease is provided, along with a discussion of the clinical pharmacology, mechanism of action and FDA indication for the relevant medication. In each case, a brief review of clinical trial data supporting drug development for each medication is provided. Additionally, guidance as to drug dosing and long-term monitoring of adverse events and pediatric efficacy is presented, to aid the clinician seeking to utilize these novel therapies in their practice, or to become familiar with the healthcare expectations for children receiving these medications through specialized multidisciplinary clinics. The availability of these targeted therapies now significantly augments treatment options for conditions in which past therapy has relied upon less specific, symptomatic medical and orthopedic care.<\/jats:p>","DOI":"10.3389\/fped.2022.1012816","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T05:27:27Z","timestamp":1665466047000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Emerging therapies for the treatment of rare pediatric bone disorders"],"prefix":"10.3389","volume":"10","author":[{"given":"Kathryn M.","family":"Thrailkill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Kalaitzoglou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Fowlkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1056\/NEJMoa1106173","article-title":"Enzyme-replacement therapy in life-threatening hypophosphatasia.","volume":"366","author":"Whyte","year":"2012","journal-title":"N Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/nrendo.2016.14","article-title":"Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment.","volume":"12","author":"Whyte","year":"2016","journal-title":"Nat Rev Endocrinol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1007\/s00223-015-0079-1","article-title":"Alkaline phosphatase and hypophosphatasia.","volume":"98","author":"Millan","year":"2016","journal-title":"Calcif Tissue Int."},{"key":"B4","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/s40265-015-0535-2","article-title":"Asfotase Alfa: a review in paediatric-onset hypophosphatasia.","volume":"76","author":"Scott","year":"2016","journal-title":"Drugs."},{"key":"B5","doi-asserted-by":"publisher","first-page":"144855","DOI":"10.1016\/j.gene.2020.144855","article-title":"Alkaline phosphatase: structure, expression and its function in bone mineralization.","volume":"754","author":"Vimalraj","year":"2020","journal-title":"Gene."},{"key":"B6","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1002\/jbmr.2110","article-title":"Calcific periarthritis as the only clinical manifestation of hypophosphatasia in middle-aged sisters.","volume":"29","author":"Guanabens","year":"2014","journal-title":"J Bone Mineral Res Offi J Am Soc Bone Mineral Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.bone.2015.02.022","article-title":"Hypophosphatasia: validation and expansion of the clinical nosology for children from 25 years experience with 173 pediatric patients.","volume":"75","author":"Whyte","year":"2015","journal-title":"Bone."},{"key":"B8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1471-2350-10-51","article-title":"Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles.","volume":"10","author":"Fauvert","year":"2009","journal-title":"BMC Med Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1002\/humu.24010","article-title":"Large-scale in vitro functional testing and novel variant scoring via protein modeling provide insights into alkaline phosphatase activity in hypophosphatasia.","volume":"41","author":"Del Angel","year":"2020","journal-title":"Hum Mutat."},{"key":"B10","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.ymgme.2017.07.010","article-title":"Monitoring guidance for patients with hypophosphatasia treated with asfotase alfa.","volume":"122","author":"Kishnani","year":"2017","journal-title":"Mol Genet Metab."},{"key":"B11","doi-asserted-by":"publisher","first-page":"13","DOI":"10.33176\/AACB-19-00031","article-title":"Hypophosphatasia: biological and clinical aspects, avenues for therapy.","volume":"41","author":"Salles","year":"2020","journal-title":"Clin Biochem Rev."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3147","DOI":"10.2147\/DDDT.S154922","article-title":"Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in therapy.","volume":"12","author":"Bowden","year":"2018","journal-title":"Drug Des Devel Ther."},{"key":"B13","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/8904_2013_224","article-title":"Outcome of perinatal hypophosphatasia in manitoba mennonites: a retrospective cohort analysis.","volume":"11","author":"Leung","year":"2013","journal-title":"JIMD Rep."},{"key":"B14","year":"2022","journal-title":"Prescribing Information."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1210\/jc.2018-02335","article-title":"Efficacy and Safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study.","volume":"104","author":"Hofmann","year":"2019","journal-title":"J Clin Endocrinol Metab."},{"key":"B16","doi-asserted-by":"publisher","first-page":"115664","DOI":"10.1016\/j.bone.2020.115664","article-title":"Pharmacodynamics of asfotase alfa in adults with pediatric-onset hypophosphatasia.","volume":"142","author":"Seefried","year":"2021","journal-title":"Bone."},{"key":"B17","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S2213-8587(18)30307-3","article-title":"Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial.","volume":"7","author":"Whyte","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e85971","DOI":"10.1172\/jci.insight.85971","article-title":"Asfotase alfa therapy for children with hypophosphatasia.","volume":"1","author":"Whyte","year":"2016","journal-title":"JCI Insight."},{"key":"B19","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.bone.2018.12.011","article-title":"Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia.","volume":"121","author":"Kishnani","year":"2019","journal-title":"Bone."},{"key":"B20","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1164\/ajrccm.166.1.at1102","article-title":"ATS statement: guidelines for the six-minute walk test.","volume":"166","year":"2002","journal-title":"Am J Respir Crit Care Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e10395","DOI":"10.1002\/jbm4.10395","article-title":"Physical function and health-related quality of life in adults treated with asfotase alfa for pediatric-onset hypophosphatasia.","volume":"4","author":"Genest","year":"2020","journal-title":"JBMR Plus."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e344","DOI":"10.4158\/ACCR-2019-0143","article-title":"Adult-onset hypophosphatasia: before and after treatment with asfotase alfa.","volume":"5","author":"Magdaleno","year":"2019","journal-title":"AACE Clin Case Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/jbm4.10052","article-title":"Fracture healing in two adult patients with hypophosphatasia after asfotase alfa therapy.","volume":"2","author":"Klidaras","year":"2018","journal-title":"JBMR Plus."},{"key":"B24","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.clinbiochem.2018.04.024","article-title":"Spurious testosterone laboratory results in a patient taking synthetic alkaline phosphatase (asfotase alfa).","volume":"58","author":"Sofronescu","year":"2018","journal-title":"Clin Biochem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1093\/jalm\/jfz007","article-title":"Interference of asfotase alfa in immunoassays employing alkaline phosphatase technology.","volume":"5","author":"Piec","year":"2020","journal-title":"J Appl Lab Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1097\/MNH.0000000000000526","article-title":"Fibroblast growth factor 23 and phosphate homeostasis.","volume":"28","author":"Balani","year":"2019","journal-title":"Curr Opin Nephrol Hypertens."},{"key":"B27","doi-asserted-by":"publisher","first-page":"bvaa151","DOI":"10.1210\/jendso\/bvaa151","article-title":"Linked hypophosphatemia: a new era in management.","volume":"4","author":"Dahir","year":"2020","journal-title":"J Endocr Soc."},{"key":"B28","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1007\/s40265-018-0905-7","article-title":"Burosumab: first global approval.","volume":"78","author":"Lamb","year":"2018","journal-title":"Drugs."},{"key":"B29","doi-asserted-by":"publisher","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 Mineral Res Offi J Am Soc Bone Mineral Res."},{"key":"B30","doi-asserted-by":"publisher","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."},{"key":"B31","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s41574-022-00662-x","article-title":"Interdisciplinary management of FGF23-related phosphate wasting syndromes: a consensus statement on the evaluation, diagnosis and care of patients with X-linked hypophosphataemia.","volume":"18","author":"Trombetti","year":"2022","journal-title":"Nat Rev Endocrinol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ando.2021.12.001","article-title":"Endocrinology of bone mineralization: an update.","volume":"83","author":"Jannin","year":"2022","journal-title":"Ann Endocrinol (Paris)."},{"key":"B33","first-page":"17","article-title":"FGF23 and associated disorders of phosphate wasting.","volume":"17","author":"Gohil","year":"2019","journal-title":"Pediatr Endocrinol Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/s41581-019-0152-5","article-title":"Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.","volume":"15","author":"Haffner","year":"2019","journal-title":"Nat Rev Nephrol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1097\/MNH.0000000000000631","article-title":"Burosumab in X-linked hypophosphatemia and perspective for chronic kidney disease.","volume":"29","author":"Balani","year":"2020","journal-title":"Curr Opin Nephrol Hypertens."},{"key":"B36","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/bcp.13763","article-title":"Pharmacological management of X-linked hypophosphataemia.","volume":"85","author":"Imel","year":"2019","journal-title":"Br J Clin Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"433","DOI":"10.5435\/JAAOS-D-14-00082","article-title":"Contemporary medical and surgical management of X-linked hypophosphatemic rickets.","volume":"23","author":"Sharkey","year":"2015","journal-title":"J Am Acad Orthop Surg."},{"key":"B38","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.ekir.2020.03.025","article-title":"An overview of rickets in children.","volume":"5","author":"Chanchlani","year":"2020","journal-title":"Kidney Int Rep."},{"key":"B39","doi-asserted-by":"publisher","first-page":"7S","DOI":"10.1177\/0022034514529150","article-title":"Rare bone diseases and their dental, oral, and craniofacial manifestations.","volume":"93","author":"Foster","year":"2014","journal-title":"J Dent Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/jbmr.3614","article-title":"High incidence of cranial synostosis and chiari i malformation in children with X-linked hypophosphatemic rickets (XLHR).","volume":"34","author":"Rothenbuhler","year":"2019","journal-title":"J Bone Mineral Res Offi J Am Soc Bone Mineral Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1210\/js.2018-00365","article-title":"The lifelong impact of X-linked hypophosphatemia: results from a burden of disease survey.","volume":"3","author":"Skrinar","year":"2019","journal-title":"J Endocr Soc."},{"key":"B42","doi-asserted-by":"publisher","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."},{"key":"B43","doi-asserted-by":"publisher","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 Mineral Res Offi J Am Soc Bone Mineral Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"E1492","DOI":"10.1210\/jc.2012-1336","article-title":"Abnormalities in muscle density and muscle function in hypophosphatemic rickets.","volume":"97","author":"Veilleux","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"key":"B45","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1007\/s00223-010-9373-0","article-title":"Phenotype presentation of hypophosphatemic rickets in adults.","volume":"87","author":"Beck-Nielsen","year":"2010","journal-title":"Calcif Tissue Int."},{"key":"B46","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1148\/radiology.171.2.2539609","article-title":"X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features.","volume":"171","author":"Hardy","year":"1989","journal-title":"Radiology."},{"key":"B47","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1097\/00005792-198911000-00002","article-title":"X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults.","volume":"68","author":"Reid","year":"1989","journal-title":"Medicine (Baltimore)."},{"key":"B48","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S0169-6009(08)80127-4","article-title":"X-linked hypophosphatemic rickets: a disease often unknown to affected patients.","volume":"24","author":"Econs","year":"1994","journal-title":"Bone Miner."},{"key":"B49","doi-asserted-by":"publisher","first-page":"230","DOI":"10.7326\/0003-4819-100-2-230","article-title":"Impaired hearing in X-linked hypophosphataemic (vitamin-D-resistant) osteomalacia.","volume":"100","author":"Davies","year":"1984","journal-title":"Ann Int Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1507\/endocrj.EJ15-0275","article-title":"Nationwide survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases in Japan: prevalence, biochemical data and treatment.","volume":"62","author":"Endo","year":"2015","journal-title":"Endocr J."},{"key":"B51","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1210\/clinem\/dgz203","article-title":"Prevalence and mortality of individuals with X-linked hypophosphatemia: a united kingdom real-world data analysis.","volume":"105","author":"Hawley","year":"2020","journal-title":"J Clin Endocrinol Metab."},{"key":"B52","year":"2022","journal-title":"Prescribing Information."},{"key":"B53","author":"Agency","year":"2018","journal-title":"Crysvita European Public Assessment Report, Summary of Product Characteristics."},{"key":"B54","doi-asserted-by":"publisher","first-page":"105208","DOI":"10.1016\/j.jbspin.2021.105208","article-title":"X-linked hypophosphatemia and burosumab: practical clinical points from the French experience.","volume":"88","author":"Bacchetta","year":"2021","journal-title":"Joint Bone Spine."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1172\/JCI72829","article-title":"Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia.","volume":"124","author":"Carpenter","year":"2014","journal-title":"J Clin Invest."},{"key":"B56","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1210\/jc.2015-1551","article-title":"Prolonged correction of serum phosphorus in adults with X-linked hypophosphatemia using monthly doses of KRN23.","volume":"100","author":"Imel","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"key":"B57","doi-asserted-by":"publisher","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."},{"key":"B58","doi-asserted-by":"publisher","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."},{"key":"B59","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3389\/fendo.2020.00338","article-title":"Clinical evidence for the benefits of burosumab therapy for X-linked hypophosphatemia (XLH) and other conditions in adults and children.","volume":"11","author":"Schindeler","year":"2020","journal-title":"Front Endocrinol (Lausanne)."},{"key":"B60","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1056\/NEJMoa1813446","article-title":"C-type natriuretic peptide analogue therapy in children with achondroplasia.","volume":"381","author":"Savarirayan","year":"2019","journal-title":"N Engl J Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/S0140-6736(20)31541-5","article-title":"Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial.","volume":"396","author":"Savarirayan","year":"2020","journal-title":"Lancet."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/j.ajhg.2012.10.014","article-title":"Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia.","volume":"91","author":"Lorget","year":"2012","journal-title":"Am J Hum Genet."},{"key":"B63","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/371252a0","article-title":"Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.","volume":"371","author":"Rousseau","year":"1994","journal-title":"Nature."},{"key":"B64","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/0092-8674(94)90302-6","article-title":"Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.","volume":"78","author":"Shiang","year":"1994","journal-title":"Cell."},{"key":"B65","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1097\/MOP.0b013e32833b7a69","article-title":"Achondroplasia: pathogenesis and implications for future treatment.","volume":"22","author":"Laederich","year":"2010","journal-title":"Curr Opin Pediatr."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-018-0972-6","article-title":"Achondroplasia: a comprehensive clinical review.","volume":"14","author":"Pauli","year":"2019","journal-title":"Orphanet J Rare Dis."},{"key":"B67","first-page":"368","article-title":"Achondroplasia is defined by recurrent G380R mutations of FGFR3.","volume":"56","author":"Bellus","year":"1995","journal-title":"Am J Hum Genet."},{"key":"B68","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1542\/peds.2020-1010","article-title":"Committee on G. health supervision for people with achondroplasia.","volume":"145","author":"Hoover-Fong","year":"2020","journal-title":"Pediatrics."},{"key":"B69","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1002\/ajmg.a.32485","article-title":"The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US.","author":"Waller","year":"2008","journal-title":"Am J Med Genet A."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1002\/ajmg.a.61289","article-title":"Epidemiology of achondroplasia: a population-based study in Europe.","volume":"179","author":"Coi","year":"2019","journal-title":"Am J Med Genet A."},{"key":"B71","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1038\/s41436-021-01287-7","article-title":"Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study.","volume":"23","author":"Savarirayan","year":"2021","journal-title":"Genet Med."},{"key":"B72","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1186\/s13023-022-02372-z","article-title":"Literature review and expert opinion on the impact of achondroplasia on medical complications and health-related quality of life and expectations for long-term impact of vosoritide: a modified Delphi study.","volume":"17","author":"Savarirayan","year":"2022","journal-title":"Orphanet J Rare Dis."},{"key":"B73","doi-asserted-by":"publisher","first-page":"368504211003782","DOI":"10.1177\/00368504211003782","article-title":"Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery.","volume":"104","author":"Savarirayan","year":"2021","journal-title":"Sci Prog."}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.1012816\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T05:27:34Z","timestamp":1665466054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.1012816\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,11]]},"references-count":73,"alternative-id":["10.3389\/fped.2022.1012816"],"URL":"https:\/\/doi.org\/10.3389\/fped.2022.1012816","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,11]]},"article-number":"1012816"}}