{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T02:56:06Z","timestamp":1785207366708,"version":"3.55.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T00:00:00Z","timestamp":1458691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005744","name":"Foundation for Pediatric Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005744","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006313","name":"Swedish Childhood Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>WNT proteins comprise a 19-member glycoprotein family that act in several developmental and regenerative processes. In bone, WNT proteins regulate osteoblast differentiation and maintain bone health by activating the canonical WNT\/\u03b2-catenin pathway. We reported a heterozygous missense mutation c.652T&amp;gt;G (p.C218G) in WNT1 exon 4 as the cause for severe early-onset, autosomal dominant osteoporosis. The initial study concerned a large Finnish family with 10 affected adults. Here we report clinical findings of the WNT1 osteoporosis in 8 children and young adults (median age 14 years; range 10 to 30 years) in two families, all with the p.C218G mutation in WNT1. Clinical assessments showed no apparent dysmorphia or features similar to typical osteogenesis imperfecta (OI). Biochemistry revealed no changes in parameters of calcium metabolism and bone turnover markers. Fracture frequencies varied, but all subjects had sustained at least one fracture and 4 had a pathological fracture history. Plain radiographs showed osteopenic appearance, loss in vertebral height, and thin diaphyses of the long bones. Bone densitometry showed the BMD to be below normal median in all subjects and the bone mass deficit seemed to be more severe in older participants. Bone histomorphometry revealed a low turnover osteoporosis in 2 subjects at ages 14 and 16 years. These findings are congruent with earlier findings in adult patients and indicate that WNT1 osteoporosis causes significant skeletal changes already in early childhood and impairs bone mass gain during pubertal years. Genetic testing of children or close relatives of affected individuals is recommended for appropriate preventive measures. \u00a9 2016 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2841","type":"journal-article","created":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T11:08:59Z","timestamp":1458731339000},"page":"1734-1742","source":"Crossref","is-referenced-by-count":54,"title":["Skeletal Characteristics of WNT1 Osteoporosis in Children and Young Adults"],"prefix":"10.1093","volume":"31","author":[{"given":"Riikka E","family":"M\u00e4kitie","sequence":"first","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics and University of HelsinkiHelsinkiFinland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Haanp\u00e4\u00e4","sequence":"additional","affiliation":[{"name":"Department of Clinical GeneticsTurku University HospitalTurkuFinland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Valta","sequence":"additional","affiliation":[{"name":"Children's HospitalUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"Pekkinen","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics and University of HelsinkiHelsinkiFinland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M","family":"Laine","sequence":"additional","affiliation":[{"name":"Department of EndocrinologyInstitute of Medicine, Sahlgrenska University Hospital and University of GothenburgGothenburgSweden"},{"name":"Folkh\u00e4lsan Institute of Genetics and University of HelsinkiHelsinkiFinland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Elina","family":"Lehesjoki","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics and University of HelsinkiHelsinkiFinland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Schalin-J\u00e4ntti","sequence":"additional","affiliation":[{"name":"Endocrinology, Abdominal CenterUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, Karolinska Institutet, and Clinical GeneticsKarolinska University HospitalStockholmSweden"},{"name":"Children's HospitalUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland"},{"name":"Folkh\u00e4lsan Institute of Genetics and University of HelsinkiHelsinkiFinland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,3,23]]},"reference":[{"issue":"12","key":"2024021014172705100_jbmr2841-bib-0001","first-page":"785","article-title":"Osteoporosis prevention, diagnosis, and therapy","volume":"285","year":"2001","journal-title":"JAMA"},{"issue":"3","key":"2024021014172705100_jbmr2841-bib-0002","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nrrheum.2011.217","article-title":"Osteoporosis, frailty and fracture: implications for case finding and therapy","volume":"8","author":"van den Bergh","year":"2012","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"2024021014172705100_jbmr2841-bib-0003","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrrheum.2009.260","article-title":"Osteoporosis: impact on health and economics","volume":"6","author":"Harvey","year":"2010","journal-title":"Nat Rev Rheumatol"},{"issue":"8","key":"2024021014172705100_jbmr2841-bib-0004","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1002\/jbmr.412","article-title":"Bone mineral accrual from 8 to 30 years of age: an estimation of peak bone mass","volume":"26","author":"Baxter-Jones","year":"2011","journal-title":"J Bone Miner Res"},{"issue":"2","key":"2024021014172705100_jbmr2841-bib-0005","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1172\/JCI117034","article-title":"Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. 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