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It is caused by heterozygous pathogenic variants in the Filamin B encoding gene (\n                    <jats:italic>FLNB<\/jats:italic>\n                    ). FLNB is a cytoskeletal protein that plays a key role in bone morphogenesis; however, the skeletal phenotype of Larsen syndrome has not been described in detail. Here, we studied the skeletal presentation in two subjects with Larsen syndrome. A case-study including a 63-year-old women and her 33-year-old daughter with Larsen syndrome, both carrying a novel\n                    <jats:italic>FLNB<\/jats:italic>\n                    c.688G\u2009&gt;\u2009T,\n                    <jats:italic>p<\/jats:italic>\n                    .(Val230Phe) variant. The bone morphologic evaluation included, radiographs, bone mineral density assessment, and high-resolution peripheral quantitative tomography (HR-pQCT). In addition, a transiliac crest bone biopsy from the mother was evaluated by \u00b5CT, histomorphometry, and in situ examination of\n                    <jats:italic>FLNB<\/jats:italic>\n                    expression within physiological human bone remodeling sites of controls. Both women were diagnosed with severe osteoporosis (T-score\u2009&lt;\u2009-5). The HR-pQCT analysis showed a low trabecular bone volume, as well as a low cortical thickness compared to a healthy cohort. Histomorphometry and \u00b5CT analysis of the iliac bone biopsy confirmed low cortical thickness, and revealed a high density of small eroded and quiescent intracortical pores. The trabecular bone remodeling was not affected, while cortical remodeling events accumulated as small eroded pores and quiescent pores with an improved infilling. The\n                    <jats:italic>FLNB<\/jats:italic>\n                    variant is associated with low bone mineral density reflecting severe osteoporosis and an altered trabecular and cortical bone structure, while bone turnover was less affected at the time of analysis.\n                  <\/jats:p>","DOI":"10.1007\/s00223-025-01436-z","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:27:44Z","timestamp":1759940864000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe Osteoporosis in Larsen Syndrome\u2014A Case Report of Bone Morphology and A Novel Filamin B (FLNB) Variant"],"prefix":"10.1007","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9421-3004","authenticated-orcid":false,"given":"Trine Maxel","family":"Juul","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7552-5974","authenticated-orcid":false,"given":"Lisbeth Koch","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2624-5677","authenticated-orcid":false,"given":"Christina M\u00f8ller","family":"Andreasen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Ejersted","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6266-6439","authenticated-orcid":false,"given":"Lars","family":"Folkestad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Brusgaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9486-0316","authenticated-orcid":false,"given":"Stinus","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-6679","authenticated-orcid":false,"given":"Jesper Skovhus","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-7276","authenticated-orcid":false,"given":"Thomas Levin","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-8910","authenticated-orcid":false,"given":"Anja Lisbeth","family":"Frederiksen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"1436_CR1","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/s0022-3476(50)80268-8","volume":"37","author":"LJ Larsen","year":"1950","unstructured":"Larsen LJ, Schottstaedt ER, Bost FC (1950) Multiple congenital dislocations associated with characteristic facial abnormality. 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