{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T15:53:58Z","timestamp":1763567638264,"version":"3.45.0"},"reference-count":11,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"NIH\/National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR077992"],"award-info":[{"award-number":["R01AR077992"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A 26-year-old man was evaluated for an elevated serum bone-specific alkaline phosphatase (BSAP). His medical history was significant for a neurodevelopmental disorder with generalized epilepsy. Symptoms included chronic pain in the ankles, hands, and right ribs, and a progressive decline in physical activity. Vitamin D deficiency was discovered, but the elevated BSAP persisted despite vitamin D replacement. Imaging studies reported diffusely increased scintigraphic uptake in the axial and appendicular skeleton, and low bone mineral density, but no radiographic sclerotic or lytic lesions. Genetic screening revealed a heterozygous pathogenic variant in the sodium voltage-gated channel \u03b1 subunit 8 gene (SCN8A) (c.2924 T&amp;gt;A; p.L975*). Loss-of-function mutations in SCN8A are responsible for neurologic disease and bone loss. Expression analysis revealed that SCN8A was present in human osteoblasts and osteocytes, but not in osteoclasts, suggesting that the voltage-gated sodium channel, Nav1.6, encoded by SCN8A, may have direct actions in bone. The patient was subsequently prescribed alendronate, resulting in a lower alkaline phosphatase and symptomatic improvement in bone pain.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf239","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T11:55:22Z","timestamp":1757591722000},"source":"Crossref","is-referenced-by-count":0,"title":["Osteoporosis Associated with\n                    <i>SCN8A<\/i>\n                    Mutation"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2678-6913","authenticated-orcid":false,"given":"Daniyeh","family":"Khurram","sequence":"first","affiliation":[{"name":"Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan School of Medicine , Ann Arbor, MI 48109 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-2709","authenticated-orcid":false,"given":"Kristyna","family":"Kupkova","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, School of Medicine, University of Virginia , Charlottesville, VA 22903 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry D","family":"Mesner","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, School of Medicine, University of Virginia , Charlottesville, VA 22903 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8860-2588","authenticated-orcid":false,"given":"Andrew T","family":"Kraftson","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan School of Medicine , Ann Arbor, MI 48109 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6748-4711","authenticated-orcid":false,"given":"Charles R","family":"Farber","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, School of Medicine, University of Virginia , Charlottesville, VA 22903 ,","place":["USA"]},{"name":"Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia , Charlottesville, VA 22903 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3755-7529","authenticated-orcid":false,"given":"Gregory A","family":"Clines","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan School of Medicine , Ann Arbor, MI 48109 ,","place":["USA"]},{"name":"Veterans Affairs Ann Arbor Healthcare System , Medicine Service, Ann Arbor, MI 48105-2399 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"issue":"Suppl 3","key":"2025111910500812900_luaf239-B1","first-page":"86","article-title":"SCN8A encephalopathy: mechanisms and models","volume":"60","author":"Meisler","year":"2019","journal-title":"Epilepsia"},{"issue":"3","key":"2025111910500812900_luaf239-B2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41583-020-00418-4","article-title":"Sodium channelopathies in neurodevelopmental disorders","volume":"22","author":"Meisler","year":"2021","journal-title":"Nat Rev Neurosci"},{"issue":"8","key":"2025111910500812900_luaf239-B3","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1002\/jbmr.4622","article-title":"Identification of known and novel long noncoding RNAs potentially responsible for the effects of bone mineral density (BMD) genomewide association study (GWAS) loci","volume":"37","author":"Abood","year":"2020","journal-title":"J Bone Miner Res"},{"issue":"1","key":"2025111910500812900_luaf239-B4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41413-023-00312-6","article-title":"Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity","volume":"12","author":"Hansen","year":"2024","journal-title":"Bone Res"},{"issue":"3","key":"2025111910500812900_luaf239-B5","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1528-1167.2006.00460.x","article-title":"Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine","volume":"47","author":"Mintzer","year":"2006","journal-title":"Epilepsia"},{"key":"2025111910500812900_luaf239-B6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.yebeh.2003.11.026","article-title":"Pathophysiology of bone loss in patients receiving anticonvulsant therapy","volume":"5","author":"Fitzpatrick","year":"2004","journal-title":"Epilepsy Behav"},{"issue":"3","key":"2025111910500812900_luaf239-B7","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s00774-004-0594-z","article-title":"Hypophosphatemic osteomalacia: a report of five cases and evaluation of bone markers","volume":"23","author":"Ros","year":"2005","journal-title":"J Bone Miner Metab"},{"issue":"7","key":"2025111910500812900_luaf239-B8","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.3390\/jcm12072714","article-title":"Osteomalacia in adults: a practical insight for clinicians","volume":"12","author":"Arboleya","year":"2023","journal-title":"J Clin Med"},{"issue":"D1","key":"2025111910500812900_luaf239-B9","doi-asserted-by":"crossref","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: the universal protein knowledgebase in 2023","volume":"51","author":"The UniProt Consortium","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2025111910500812900_luaf239-B10","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.bone.2017.06.025","article-title":"Severe bone loss and multiple fractures in SCN8A-related epileptic encephalopathy","volume":"103","author":"Rolvien","year":"2017","journal-title":"Bone"},{"issue":"6","key":"2025111910500812900_luaf239-B11","doi-asserted-by":"crossref","first-page":"a001073","DOI":"10.1101\/mcs.a001073","article-title":"SCN8A mutation in a child presenting with seizures and developmental delays","volume":"2","author":"Malcolmson","year":"2016","journal-title":"Mol Case Stud"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/12\/luaf239\/65393094\/luaf239.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/12\/luaf239\/65393094\/luaf239.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T15:50:14Z","timestamp":1763567414000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luaf239\/8327936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":11,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,10,27]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luaf239","relation":{},"ISSN":["2755-1520"],"issn-type":[{"value":"2755-1520","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,10,27]]},"article-number":"luaf239"}}