{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:45:33Z","timestamp":1788864333839,"version":"build-2803163510"},"reference-count":31,"publisher":"The Endocrine Society","issue":"10","funder":[{"DOI":"10.13039\/100017540","name":"Division of Intramural Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"NICHD","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Our study explores the impact of human parathyroid hormone (PTH) 1-34 injections (PTH therapy) on growth, areal bone mineral density (BMD), and bone quality (measured by trabecular bone score, TBS) in hypoparathyroidism due to autoimmune polyendocrine syndrome type 1 (APS-1) or an activating variant of the calcium sensing receptor (CaR).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To assess associations of (1) age and PTH therapy duration with age-standardized Z-scores for height (HAZ), BMD (BMD-Z), and TBS (TBS-Z) in CaR or APS-1, and (2) APS-1 disease severity with BMD-Z and TBS-Z.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This secondary analysis pooled linear growth and lumbar spine (LS) dual-energy x-ray absorptiometry data from studies of hypoparathyroidism with mean baseline age of 13.7 \u00b1 5.5 years. Comparing the 2 diagnostic etiologies (18 APS-1 and 9 CaR), we examined the impact of age and PTH duration on HAZ, LS-BMD-Z, and LS-TBS-Z using longitudinal mixed-effects modeling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>During PTH therapy, mean HAZ remained below 0 in the APS-1 group at all ages, whereas HAZ increased in the CaR group (age by group interaction P &amp;lt; .0001). Mean LS-BMD-Z were normal (BMD-Z: 0 \u00b1 1) for both groups. Mean LS-TBS-Z were near or above 0 and differed by group; CaR showed an upward trajectory according to time on PTH whereas the APS-1 group maintained a LS-TBS-Z of approximately 0 (time by group interaction P = .02). The APS-1 group with greater disease severity (\u22657 manifestations) had lower LS-BMD-Z and LS-TBS-Z than the less severe APS-1 or CaR groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study highlights distinct growth and BMD patterns in APS-1 and CaR and underscores the need for careful monitoring and tailored treatment strategies to optimize growth and bone health.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf065","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T12:22:51Z","timestamp":1738239771000},"page":"2810-2817","source":"Crossref","is-referenced-by-count":2,"title":["Bone Health and Linear Growth in Children With Familial Hypoparathyroidism Treated With Human Parathyroid Hormone 1-34"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8261-5188","authenticated-orcid":false,"given":"Karen K","family":"Winer","sequence":"first","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) , Bethesda, MD 20892-7002 ,","place":["USA"]},{"name":"Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babette S","family":"Zemel","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kelly","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C","family":"Reynolds","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, Radiology and Imaging Sciences , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Pechacek","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taura","family":"Webb","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Hans","sequence":"additional","affiliation":[{"name":"Center of Bone Diseases, Bone and Joint Department, Lausanne University Hospital and University of Lausanne , Av. Pierre Decker 4, Lausanne 1011 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail S","family":"Lionakis","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy & Infectious Diseases (NIAID), National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi J","family":"Kalkwarf","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hepatology and Nutrition, Cincinnati Children\u2019s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"2025091917025782200_dgaf065-B1","doi-asserted-by":"crossref","first-page":"115977","DOI":"10.1016\/j.bone.2021.115977","article-title":"Therapy with PTH 1-34 or calcitriol and calcium in diverse etiologies of hypoparathyroidism over 27 years at a single tertiary care center","volume":"149","author":"Winer","year":"2021","journal-title":"Bone"},{"key":"2025091917025782200_dgaf065-B2","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jpeds.2018.08.010","article-title":"Long-Term parathyroid hormone 1-34 replacement therapy in children with hypoparathyroidism","volume":"203","author":"Winer","year":"2018","journal-title":"J Pediatr"},{"issue":"1","key":"2025091917025782200_dgaf065-B3","doi-asserted-by":"crossref","first-page":"17055","DOI":"10.1038\/nrdp.2017.55","article-title":"Hypoparathyroidism [published correction appears in Nat Rev Dis Primers. 2017 Oct 05;3:17080. doi: 10.1038\/nrdp.2017.80]","volume":"3","author":"Mannstadt","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"4","key":"2025091917025782200_dgaf065-B4","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1007\/s10875-022-01254-0","article-title":"Prevalence of APECED-like clinical disease in an electronic health record database, USA","volume":"42","author":"Ricotta","year":"2022","journal-title":"J Clin Immunol"},{"issue":"6","key":"2025091917025782200_dgaf065-B5","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.ajhg.2020.04.006","article-title":"Familial hypocalciuric hypercalcemia type 1 and autosomal-dominant hypocalcemia type 1: prevalence in a large healthcare population","volume":"106","author":"Dershem","year":"2020","journal-title":"Am J Hum Genet"},{"issue":"13","key":"2025091917025782200_dgaf065-B6","doi-asserted-by":"crossref","first-page":"e88782","DOI":"10.1172\/jci.insight.88782","article-title":"Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"1","author":"Ferre","year":"2016","journal-title":"JCI Insight"},{"issue":"04","key":"2025091917025782200_dgaf065-B7","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1055\/s-0036-1592429","article-title":"Metabolic bone disease in patients with malabsorption","volume":"20","author":"Phan","year":"2016","journal-title":"Semin Musculoskelet Radiol"},{"issue":"1","key":"2025091917025782200_dgaf065-B8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1097\/MPG.0b013e31821988a3","article-title":"Skeletal health of children and adolescents with inflammatory bowel disease","volume":"53","author":"Pappa","year":"2011","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2025091917025782200_dgaf065-B9","doi-asserted-by":"crossref","first-page":"576","DOI":"10.3389\/fendo.2020.00576","article-title":"Glucocorticoid-Induced osteoporosis: why kids are different","volume":"11","author":"Ward","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"5","key":"2025091917025782200_dgaf065-B10","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/j.1365-2265.2006.02495.x","article-title":"Bone health in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED): findings in 25 adults","volume":"64","author":"M\u00e4kitie","year":"2006","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2025091917025782200_dgaf065-B11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3389\/fendo.2020.00109","article-title":"Severe phenotype of APECED (APS1) increases risk for structural bone alterations","volume":"11","author":"Laakso","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"2025091917025782200_dgaf065-B12","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jocd.2017.06.019","article-title":"Use of trabecular bone score (TBS) as a complementary approach to dual-energy X-ray absorptiometry (DXA) for fracture risk assessment in clinical practice","volume":"20","author":"Shevroja","year":"2017","journal-title":"J Clin Densitom"},{"issue":"2","key":"2025091917025782200_dgaf065-B13","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s12020-014-0280-4","article-title":"Utility of the trabecular bone score (TBS) in secondary osteoporosis","volume":"47","author":"Ulivieri","year":"2014","journal-title":"Endocrine"},{"issue":"2","key":"2025091917025782200_dgaf065-B14","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s00198-016-3750-0","article-title":"Bone imaging in hypoparathyroidism","volume":"28","author":"Silva","year":"2017","journal-title":"Osteoporos Int"},{"issue":"4","key":"2025091917025782200_dgaf065-B15","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/jbmr.4520","article-title":"Trabecular bone score reference values for children and adolescents according to age, sex, and ancestry","volume":"37","author":"Kalkwarf","year":"2022","journal-title":"J Bone Miner Res"},{"issue":"6","key":"2025091917025782200_dgaf065-B16","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1210\/jc.2009-2464","article-title":"Long-term treatment of 12 children with chronic hypoparathyroidism: a randomized trial comparing synthetic human parathyroid hormone 1-34 versus calcitriol and calcium","volume":"95","author":"Winer","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"issue":"10","key":"2025091917025782200_dgaf065-B17","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1210\/jc.2011-1111","article-title":"Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study","volume":"96","author":"Zemel","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2025091917025782200_dgaf065-B18","first-page":"1","article-title":"CDC growth charts: United States","volume":"314","author":"Kuczmarski","year":"2000","journal-title":"Adv Data"},{"issue":"3","key":"2025091917025782200_dgaf065-B19","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1210\/jc.2009-2057","article-title":"Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children","volume":"95","author":"Zemel","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2025091917025782200_dgaf065-B20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00467-009-1249-z","article-title":"Official positions of the International Society for Clinical Densitometry (ISCD) on DXA evaluation in children and adolescents","volume":"25","author":"Bianchi","year":"2010","journal-title":"Pediatr Nephrol"},{"issue":"4","key":"2025091917025782200_dgaf065-B21","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/jbmr.4786","article-title":"Trabecular bone score (TBS) varies with correction for tissue thickness versus body mass index: implications when using pediatric reference norms","volume":"38","author":"Valenzuela Riveros","year":"2023","journal-title":"J Bone Miner Res"},{"issue":"4","key":"2025091917025782200_dgaf065-B22","first-page":"1283","article-title":"Lumbar spine bone mineral apparent density in children: results from the bone mineral density in childhood study","volume":"104","author":"Kindler","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"2025091917025782200_dgaf065-B23","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/978-3-030-29433-5_7","volume-title":"Hypoparathyroidism","author":"Winer","year":"2020"},{"issue":"8","key":"2025091917025782200_dgaf065-B24","doi-asserted-by":"crossref","first-page":"e198918","DOI":"10.1001\/jamanetworkopen.2019.8918","article-title":"Association between age at puberty and bone accrual from 10 to 25 years of age","volume":"2","author":"Elhakeem","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"3","key":"2025091917025782200_dgaf065-B25","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/jbmr.3320","article-title":"Genetically determined later puberty impacts lowered bone mineral density in childhood and adulthood","volume":"33","author":"Cousminer","year":"2018","journal-title":"J Bone Miner Res"},{"issue":"11","key":"2025091917025782200_dgaf065-B26","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1007\/s00198-021-05966-8","article-title":"Fracture risk in hypoparathyroidism: a systematic review and meta-analysis","volume":"32","author":"Pal","year":"2021","journal-title":"Osteoporos Int"},{"issue":"4","key":"2025091917025782200_dgaf065-B27","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nrendo.2016.153","article-title":"Mechanisms of diabetes mellitus-induced bone fragility","volume":"13","author":"Napoli","year":"2017","journal-title":"Nat Rev Endocrinol"},{"issue":"8","key":"2025091917025782200_dgaf065-B28","doi-asserted-by":"crossref","first-page":"e0290812","DOI":"10.1371\/journal.pone.0290812","article-title":"Association of trabecular bone score and bone mineral apparent density with the severity of bone fragility in children and adolescents with osteogenesis imperfecta: a cross-sectional study","volume":"18","author":"Ohata","year":"2023","journal-title":"PLoS One"},{"issue":"11","key":"2025091917025782200_dgaf065-B29","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1007\/s00431-023-05157-z","article-title":"Trabecular bone score in assessing bone mineralization status in children with End- stage renal disease: a promising tool","volume":"182","author":"Salem","year":"2023","journal-title":"Eur J Pediatr"},{"issue":"20","key":"2025091917025782200_dgaf065-B30","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1056\/NEJMoa2312665","article-title":"The role of interferon-\u03b3 in autoimmune polyendocrine syndrome type 1","volume":"390","author":"Oikonomou","year":"2024","journal-title":"N Engl J Med"},{"issue":"20","key":"2025091917025782200_dgaf065-B31","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1056\/NEJMe2403419","article-title":"JAK inhibition immunotherapy for APS-1","volume":"390","author":"Su","year":"2024","journal-title":"N Engl J Med"}],"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\/dgaf065\/61703068\/dgaf065.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/10\/2810\/61703068\/dgaf065.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/10\/2810\/61703068\/dgaf065.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T21:03:09Z","timestamp":1758315789000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/10\/2810\/7990880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":31,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,1,30]]},"published-print":{"date-parts":[[2025,9,16]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaf065","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10]]},"published":{"date-parts":[[2025,1,30]]}}}