{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:15:16Z","timestamp":1755695716897,"version":"3.41.2"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Osteoclasts are essential for bone resorption, playing a crucial role in skeletal development, homeostasis, and remodeling. Their differentiation depends on the RANK receptor encoded by the TNFRSF11A gene, with defects in this gene linked to osteoclast-poor sclerosing skeletal dysplasias. This report presents a 37-yr-old woman with normal height, valgus deformities that were treated surgically, frequent fractures, scoliosis, mildly elevated BMD, sclerotic diaphyseal bone, and metaphyseal widening. Initially suspected of having dysosteosclerosis, her diagnosis shifted toward Pyle disease due to the valgus deformity and prominent metaphyseal widening and translucency. Genetic analysis identified 2 pathogenic TNFRSF11A variants: a nonsense mutation c.1093G&amp;gt;T, p.(Glu365*) and a frameshift mutation c.1266_1268delinsCC, p.(Leu422Phefs*104). Thus, genetic and clinical assessment converged on the diagnosis of a mild form of dysosteosclerosis. Both mutations introduced premature stop codons but escaped complete nonsense-mediated decay, potentially permitting residual protein function. Analysis of patient-derived osteoclasts cultured on glass surfaces showed partial differentiation. However, in vitro resorptive function was strongly impaired, which was clinically reflected by reduced serum concentration of the bone resorption marker CTx. Despite this impairment, the retained residual resorptive function likely explains the patient\u2019s relatively mild clinical presentation. These findings underscore the complex genetic interactions that affect osteoclast function, leading to a spectrum of phenotypes in osteoclast-related bone disorders.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae179","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T15:50:21Z","timestamp":1736351421000},"source":"Crossref","is-referenced-by-count":1,"title":["Paradoxical combination of osteosclerosis and osteopenia in an adult woman with biallelic <i>TNFRSF11A<\/i> loss-of-function variants escaping nonsense-mediated decay"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8719-1822","authenticated-orcid":false,"given":"Dario","family":"Gajewski","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen , 37073 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Floriane","family":"Hennig","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen , 37073 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Gr\u00fcn","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen , 37073 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heide","family":"Siggelkow","sequence":"additional","affiliation":[{"name":"MVZ Endokrinologikum G\u00f6ttingen , 37075 G\u00f6ttingen ,","place":["Germany"]},{"name":"Department of Trauma, Orthopedics and Reconstructive Surgery, University Medical Center G\u00f6ttingen , 37075 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svenja","family":"Vishnolia","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen , 37073 G\u00f6ttingen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard","family":"Bastian","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, Hospital Leverkusen , 51375 Leverkusen ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Taipaleenm\u00e4ki","sequence":"additional","affiliation":[{"name":"Institute of Musculoskeletal Medicine, LMU University Hospital, LMU Munich , 82152 Planegg-Martinsried ,","place":["Germany"]},{"name":"Musculoskeletal University Center Munich, LMU University Hospital, LMU Munich , 82152 Planegg-Martinsried ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ansgar","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Ulm , 89075 Ulm 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