{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T16:35:06Z","timestamp":1775493306667,"version":"3.50.1"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T00:00:00Z","timestamp":1615161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>To investigate the growth velocity-improving effects of vitamin D replacement therapy in pediatric patients diagnosed with vitamin D deficiency and insufficiency.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Study design<\/jats:title>\n<jats:p>A retrospective cohort study was conducted in 34 pediatric patients diagnosed with vitamin D deficiency\/insufficiency. Based on the clinical findings, the subjects were divided into two groups: a bowed leg (BL) group and a non-bowed leg (non-BL) group. After the initiation of alfacalcidol, the standard deviation score (SDS) of their heights, weights and growth velocities in each group were monitored.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The median age at the first visit was significantly lesser in the BL group (1.58 years old [interquartile range (IQR): 1.33, 2.17]) than that in the non-BL group (3.00 years old [IQR: 2.33, 3.67]). On the contrary, the SDS for height was significantly lower in the non-BL group (-2.27 [IQR: -2.63, -1.94]) than that in the BL group (-1.37 [IQR: -1.91, -1.07]). One-year treatment with alfacalcidol showed significant improvements in both height SDSs and growth velocity SDSs not only in the BL group but also in the non-BL group.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The current study revealed that vitamin D replacement therapy improved the growth rate in children with vitamin D deficiency\/insufficiency, regardless of the presence of BL. This study emphasizes the importance of assessing the vitamin D status in children with poor growth rates and suggests that alfacalcidol could be a valid option for the treatment of short stature.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0247886","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T18:27:28Z","timestamp":1615228048000},"page":"e0247886","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alfacalcidol improves the growth velocity in children with vitamin D deficiency\/insufficiency: A single center retrospective cohort study"],"prefix":"10.1371","volume":"16","author":[{"given":"Satoshi","family":"Miyagaki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihoko","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Ota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Kawabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidechika","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Oka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1271-1577","authenticated-orcid":true,"given":"Jun","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"issue":"6","key":"pone.0247886.ref001","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1507\/endocrj.EJ18-0008","article-title":"Incidence rate and characteristics of symptomatic vitamin D deficiency in children: a nationwide survey in Japan","volume":"65","author":"T Kubota","year":"2018","journal-title":"Endocr J"},{"issue":"2","key":"pone.0247886.ref002","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3177\/jnsv.64.99","article-title":"Current Vitamin D Status in Healthy Japanese Infants and Young Children","volume":"64","author":"S Nakano","year":"2018","journal-title":"J Nutr Sci Vitaminol (Tokyo)."},{"issue":"1","key":"pone.0247886.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00774-016-0805-4","article-title":"Assessment criteria for vitamin D deficiency\/insufficiency in Japan: proposal by an expert panel supported by the Research Program of Intractable Diseases, Ministry of Health, Labour and Welfare, Japan, the Japanese Society for Bone and Mineral Research and the Japan Endocrine Society [Opinion]","volume":"35","author":"R Okazaki","year":"2017","journal-title":"J Bone Miner Metab"},{"issue":"1","key":"pone.0247886.ref004","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1186\/s13104-018-3903-7","article-title":"Vitamin D levels in a pediatric population of a primary care centre: a public health problem?","volume":"11","author":"JM Fernandez Bustillo","year":"2018","journal-title":"BMC Res Notes"},{"issue":"5","key":"pone.0247886.ref005","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s00431-015-2524-6","article-title":"Vitamin D in childhood and adolescence: an expert position statement","volume":"174","author":"G Saggese","year":"2015","journal-title":"Eur J Pediatr"},{"issue":"3","key":"pone.0247886.ref006","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1515\/jpem-2017-0391","article-title":"Vitamin D deficiency in childhood: old lessons and current challenges","volume":"31","author":"R Antonucci","year":"2018","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"4","key":"pone.0247886.ref007","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.beem.2011.06.010","article-title":"The role of vitamin D in paediatric bone health","volume":"25","author":"JM Pettifor","year":"2011","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"2","key":"pone.0247886.ref008","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s00223-012-9615-4","article-title":"Vitamin D and bone health in childhood and adolescence","volume":"92","author":"T Winzenberg","year":"2013","journal-title":"Calcif Tissue Int"},{"key":"pone.0247886.ref009","first-page":"28","article-title":"Today\u2019s nutritional deficiencies- Vitamin D deficiency","volume":"86","author":"K Ozono","year":"2012","journal-title":"Vitamins (Japan)."},{"issue":"4","key":"pone.0247886.ref010","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1111\/mcn.12187","article-title":"Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity","volume":"12","author":"M Zerofsky","year":"2016","journal-title":"Matern Child Nutr"},{"issue":"11","key":"pone.0247886.ref011","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1038\/ejcn.2010.156","article-title":"Calcium and vitamin D intake and biochemical tests in short-stature children and adolescents","volume":"64","author":"AL Bueno","year":"2010","journal-title":"Eur J Clin Nutr"},{"issue":"4","key":"pone.0247886.ref012","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1297\/cpe.16.85","article-title":"Target height and target range for Japanese children: revisited","volume":"16","author":"T Ogata","year":"2007","journal-title":"Clin Pediatr Endocrinol"},{"issue":"2","key":"pone.0247886.ref013","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1442-200X.1992.tb00951.x","article-title":"Standards for growth and growth velocity in Turner\u2019s syndrome","volume":"34","author":"S Suwa","year":"1992","journal-title":"Acta Paediatr Jpn"},{"issue":"4","key":"pone.0247886.ref014","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1442-200X.2008.02700.x","article-title":"Nutritional rickets and z scores for height in the United Arab Emirates: to D or not to D?","volume":"50","author":"J Rajah","year":"2008","journal-title":"Pediatr Int"},{"issue":"5","key":"pone.0247886.ref015","first-page":"e0175237","article-title":"Vitamin D supplementation and growth in urban Mongol school children: Results from two randomized clinical trials","volume":"12","author":"D Ganmaa","year":"2017"},{"issue":"2","key":"pone.0247886.ref016","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1046\/j.1328-8067.2001.01514.x","article-title":"Case of incidentally diagnosed vitamin D deficiency rickets: a review of literature from Japan and a proposal for reintroduction of vitamin D2","volume":"44","author":"K Nishikura","year":"2002","journal-title":"Pediatr Int"},{"issue":"8","key":"pone.0247886.ref017","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1136\/adc.2003.031385","article-title":"Presentation of vitamin D deficiency","volume":"89","author":"S Ladhani","year":"2004","journal-title":"Arch Dis Child"},{"issue":"2","key":"pone.0247886.ref018","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1442-200x.2005.02041.x","article-title":"Vitamin D deficiency rickets caused by improper lifestyle in Japanese children","volume":"47","author":"K Miyako","year":"2005","journal-title":"Pediatr Int"},{"issue":"7","key":"pone.0247886.ref019","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1136\/adc.2006.095075","article-title":"Incidence of symptomatic vitamin D deficiency","volume":"91","author":"AL Callaghan","year":"2006","journal-title":"Arch Dis Child"},{"issue":"2","key":"pone.0247886.ref020","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1503\/cmaj.061377","article-title":"Vitamin D-deficiency rickets among children in Canada","volume":"177","author":"LM Ward","year":"2007","journal-title":"CMAJ"},{"issue":"4","key":"pone.0247886.ref021","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/j.1442-200X.2009.02834.x","article-title":"Prevalence and risk factors of vitamin D deficiency rickets in Hokkaido","volume":"51","author":"K Matsuo","year":"2009","journal-title":"Japan. Pediatr Int"},{"issue":"210","key":"pone.0247886.ref022","first-page":"58","article-title":"Clinical, biochemical and radiological manifestations of severe vitamin d deficiency in adolescents versus children: response to therapy","author":"A Soliman","year":"2012","journal-title":"Georgian Med News"},{"issue":"4","key":"pone.0247886.ref023","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/1753-6405.12390","volume":"39","author":"BJ Wheeler","year":"2015","journal-title":"Aust N Z J Public Health"},{"issue":"6","key":"pone.0247886.ref024","first-page":"1321","article-title":"Causes of short stature in Pakistani children found at an Endocrine Center","volume":"32","author":"A Jawa","year":"2016","journal-title":"Pak J Med Sci"},{"issue":"6","key":"pone.0247886.ref025","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1080\/07315724.2008.10719746","article-title":"Vitamin D supplementation during lactation to support infant and mothe","volume":"27","author":"SN Taylor","year":"2008","journal-title":"J Am Coll Nutr"},{"key":"pone.0247886.ref026","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev.nutr.012809.104807","article-title":"Vitamin D in pregnancy and lactation in humans","volume":"31","author":"PM Brannon","year":"2011","journal-title":"Annu Rev Nutr"},{"key":"pone.0247886.ref027","doi-asserted-by":"crossref","first-page":"f1169","DOI":"10.1136\/bmj.f1169","article-title":"Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies","volume":"346","author":"F Aghajafari","year":"2013","journal-title":"BMJ"},{"issue":"45","key":"pone.0247886.ref028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta18450","article-title":"Vitamin D supplementation in pregnancy: a systematic review.","volume":"18","author":"NC Harvey","year":"2014","journal-title":"Health Technol Assess"},{"issue":"3","key":"pone.0247886.ref029","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1054\/clnu.2001.0397","article-title":"Insulin-like growth factor 1 (IGF-1), a nutritional marker in patients with eating disorders","volume":"20","author":"L Caregaro","year":"2001","journal-title":"Clin Nutr"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0247886","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T18:28:02Z","timestamp":1615228082000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0247886"}},"subtitle":[],"editor":[{"given":"Kazumichi","family":"Fujioka","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,3,8]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0247886","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,8]]}}}