{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:06:55Z","timestamp":1772190415224,"version":"3.50.1"},"reference-count":23,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008484","name":"BioMarin Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Achondroplasia is a skeletal dysplasia associated with multisystem complications including genu varum, which causes pain and limits mobility. Vosoritide, a targeted treatment for achondroplasia, improves growth in children and has an established safety profile, but its effect on genu varum is unclear. Data were collected from 183 participants from randomized, double-blind, placebo-controlled phase 2 (CANOPY ACH-2I [111-206; NCT03583697]) and phase 3 (CANOPY ACH-3 [111-301; NCT03197766]) studies evaluating vosoritide (weight-based dose of 15 or 30\u2005\u00b5g\/kg\/day) in children aged 0-5 and &amp;gt;5 years, respectively. Anterior\/posterior lower limb radiographs were taken at baseline and 1 year to measure parameters associated with genu varum. Differences in least-squares mean (LSM) change from baseline were calculated for vosoritide vs placebo using an analysis of covariance model. In both studies, age at treatment initiation and sex distribution were generally balanced between vosoritide and placebo (except 58% males received vosoritide in CANOPY ACH-2I). After 1 year of vosoritide treatment vs placebo, tibial bowing decreased in children who initiated treatment aged &amp;lt;5 years (n = 40) and remained stable in those \u22655 years (n = 57). Vosoritide-treated participants with evidence of abnormal fibular growth at baseline had reduced overall and distal fibular overgrowth vs placebo. Children aged \u22655 years improved in ankle joint to distal fibula physis distance (difference in LSM change from baseline, \u22120.07, P = .010) and fibula\/tibia ratio (\u22120.025, P &amp;lt; .0001), and children aged 2-5 years had improved fibula\/tibia ratio (\u22120.033, P = .0032). Preliminary results suggest vosoritide may improve or limit genu varum in children with achondroplasia.<\/jats:p>","DOI":"10.1210\/jendso\/bvag024","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:43:13Z","timestamp":1770295393000},"source":"Crossref","is-referenced-by-count":0,"title":["Effect of vosoritide on genu varum in children with achondroplasia after 1 year in randomized placebo-controlled trials"],"prefix":"10.1210","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1028-5416","authenticated-orcid":false,"given":"Klane K","family":"White","sequence":"first","affiliation":[{"name":"Children's Hospital Colorado , Aurora, CO 80045 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melita","family":"Irving","sequence":"additional","affiliation":[{"name":"Guy's and St. Thomas' NHS Foundation Trust, Evelina Children's Hospital , London SE1 7EH ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swati","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"BioMarin (UK) Ltd , London WC1A 2SL ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Rivat","sequence":"additional","affiliation":[{"name":"BioMarin (UK) Ltd , London WC1A 2SL ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Sabir","sequence":"additional","affiliation":[{"name":"BioMarin (UK) Ltd , London WC1A 2SL ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Dee","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc. , Novato, CA 94949 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Savarirayan","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute, Royal Children's Hospital and University of Melbourne , Parkville, Victoria 3052 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"issue":"9","key":"2026022705062728100_bvag024-B1","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1136\/jmg.35.9.705","article-title":"Medical complications of achondroplasia: a multicentre patient review","volume":"35","author":"Hunter","year":"1998","journal-title":"J Med Genet"},{"issue":"3","key":"2026022705062728100_bvag024-B2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41574-021-00595-x","article-title":"International consensus statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia","volume":"18","author":"Savarirayan","year":"2022","journal-title":"Nat Rev Endocrinol"},{"issue":"1","key":"2026022705062728100_bvag024-B3","doi-asserted-by":"crossref","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"},{"issue":"5","key":"2026022705062728100_bvag024-B4","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/18632521241269340","article-title":"Achondroplasia current concept of orthopaedic management","volume":"18","author":"Mindler","year":"2024","journal-title":"J Child Orthop"},{"issue":"1","key":"2026022705062728100_bvag024-B5","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13023-023-02738-x","article-title":"Achondroplasia natural history study (CLARITY): 60-year experience in orthopedic surgery from four skeletal dysplasia centers","volume":"18","author":"Nahm","year":"2023","journal-title":"Orphanet J Rare Dis"},{"issue":"5","key":"2026022705062728100_bvag024-B6","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1097\/BPO.0b013e3181aa24a8","article-title":"Physeal stapling versus 8-plate hemiepiphysiodesis for guided correction of angular deformity about the knee","volume":"29","author":"Wiemann","year":"2009","journal-title":"J Pediatr Orthop"},{"key":"2026022705062728100_bvag024-B7","first-page":"chap 19","volume-title":"Pediatric Lower Limb Deformities","author":"Thacker","year":"2024"},{"issue":"1","key":"2026022705062728100_bvag024-B8","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/01241398-200201000-00023","article-title":"Observations on the cause of bowlegs in achondroplasia","volume":"22","author":"Stanley","year":"2002","journal-title":"J Pediatr Orthop"},{"key":"2026022705062728100_bvag024-B9","volume-title":"Prescribing Information","author":"Voxzogo (vosoritide)","year":"2023"},{"key":"2026022705062728100_bvag024-B10","volume-title":"Summary of Product Characteristics","author":"European Medicines Agency. Voxzogo\u00ae","year":"2021"},{"issue":"12","key":"2026022705062728100_bvag024-B11","doi-asserted-by":"crossref","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"},{"issue":"12","key":"2026022705062728100_bvag024-B12","doi-asserted-by":"crossref","first-page":"101274","DOI":"10.1016\/j.gim.2024.101274","article-title":"Persistent growth-promoting effects of vosoritide in children with achondroplasia are accompanied by improvements in physical and social aspects of health-related quality of life","volume":"26","author":"Savarirayan","year":"2024","journal-title":"Genet Med"},{"issue":"4","key":"2026022705062728100_bvag024-B13","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S2352-4642(23)00310-3","article-title":"New treatments for children with achondroplasia","volume":"8","author":"Savarirayan","year":"2024","journal-title":"Lancet Child Adolesc Health"},{"issue":"8","key":"2026022705062728100_bvag024-B14","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/BPO.0000000000002980","article-title":"Changes in the alignment of the spine and lower limb in children with achondroplasia treated with vosoritide: a single-center, 1-year follow-up prospective study","volume":"45","author":"Sawamura","year":"2025","journal-title":"J Pediatr Orthop"},{"issue":"1","key":"2026022705062728100_bvag024-B15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S2352-4642(23)00265-1","article-title":"Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"8","author":"Savarirayan","year":"2024","journal-title":"Lancet Child Adolesc Health"},{"issue":"10252","key":"2026022705062728100_bvag024-B16","doi-asserted-by":"crossref","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"},{"issue":"4","key":"2026022705062728100_bvag024-B17","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/01241398-199607000-00002","article-title":"Hemiepiphyseal stapling for knee deformities in children younger than 10 years: a preliminary report","volume":"16","author":"Mielke","year":"1996","journal-title":"J Pediatr Orthop"},{"issue":"6","key":"2026022705062728100_bvag024-B18","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1302\/2058-5241.6.210015","article-title":"Radiological assessment of lower limb alignment","volume":"6","author":"Marques Luis","year":"2021","journal-title":"EFORT Open Rev"},{"issue":"4","key":"2026022705062728100_bvag024-B19","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1097\/01.bpo.0000217712.42115.e6","article-title":"Dynamic lower extremity alignment in children with achondroplasia","volume":"26","author":"Inan","year":"2006","journal-title":"J Pediatr Orthop"},{"issue":"1","key":"2026022705062728100_bvag024-B20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1302\/0301-620X.89B1.18223","article-title":"Development of genu varum in achondroplasia: relation to fibular overgrowth","volume":"89","author":"Lee","year":"2007","journal-title":"J Bone Joint Surg Br"},{"key":"2026022705062728100_bvag024-B21","author":"National Library of Medicine"},{"key":"2026022705062728100_bvag024-B22","author":"National Library of Medicine"},{"issue":"3","key":"2026022705062728100_bvag024-B23","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1097\/01.bpo.0000203013.04272.b6","article-title":"Genu varum in achondroplasia","volume":"26","author":"Ain","year":"2006","journal-title":"J Pediatr Orthop"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jes\/advance-article-pdf\/doi\/10.1210\/jendso\/bvag024\/66804565\/bvag024.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/10\/3\/bvag024\/66804565\/bvag024.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jes\/article-pdf\/10\/3\/bvag024\/66804565\/bvag024.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:06:35Z","timestamp":1772186795000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/doi\/10.1210\/jendso\/bvag024\/8467188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,2,6]]}},"URL":"https:\/\/doi.org\/10.1210\/jendso\/bvag024","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,2,6]]},"article-number":"bvag024"}}