{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T05:05:14Z","timestamp":1767589514821,"version":"3.48.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["322647"],"award-info":[{"award-number":["322647"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sigrid Jus\u00e9lius Foundation, Folkh\u00e4lsan Research Foundation, Novo Nordisk Foundation","award":["NNF23OC0084405"],"award-info":[{"award-number":["NNF23OC0084405"]}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2022-00800"],"award-info":[{"award-number":["2022-00800"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010113","name":"Wilhelm och Else Stockmanns Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010113","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jane and Aatos Erkko Foundation, Medicinska Underst\u00f6dsf\u00f6reningen Liv och H\u00e4lsa rf"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,30]]},"abstract":"<jats:title>Vignette<\/jats:title>\n                  <jats:p>Early-onset osteoporosis (EOOP) is diagnosed in premenopausal women or men under 50\u00a0yr of age when DXA-derived BMD is low (Z-score\u2009\u2264\u2009\u22122.0 or T-score\u2009\u2264\u2009\u22122.5) in the presence of a fragility fracture or a chronic disease. In young adult patients, it is essential to recognize EOOP and identify the underlying cause, including possible genetic defects, to optimize tailored treatments. Among monogenic causes, WNT1-related osteoporosis has been described in children and adults. We present two adults, a 27-yr-old male and his mother, who had no skeletal symptoms in childhood but presented as adults with back pain. Further studies revealed low BMD and multiple spinal fragility fractures, leading to rapid height loss and progressive kyphosis. Biochemistry was largely normal, but bone biopsies showed impaired bone metabolism with low bone turnover. Both were found to harbor a previously described pathogenic heterozygous variant in WNT1, which leads to impaired WNT signaling. We describe the challenges in their clinical care, sequence of treatments, and outcome. These patients highlight the value of a correct genetic diagnosis to better understand the mechanisms behind low bone mass and to enable early intervention. Furthermore, our study emphasizes the need for anabolic treatment options for both males and females with EOOP, and the importance of long-term treatment planning, including an exit strategy.<\/jats:p>","DOI":"10.1093\/jbmr\/zjaf150","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:26:59Z","timestamp":1761222419000},"page":"85-90","source":"Crossref","is-referenced-by-count":0,"title":["Severe early-onset osteoporosis due to heterozygous\n                    <i>WNT1<\/i>\n                    variants in adults: a clinical and therapeutic challenge"],"prefix":"10.1093","volume":"41","author":[{"given":"Eeva M","family":"Ryh\u00e4nen","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions) , 00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riikka E","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital and University of Helsinki , 00290 Helsinki ,","place":["Finland"]},{"name":"Faculty of Medicine, University of Helsinki , 00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuula","family":"Pekkarinen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions) , 00290 Helsinki ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heikki","family":"Kr\u00f6ger","sequence":"additional","affiliation":[{"name":"Kuopio Musculoskeletal Research Unit (KMRU), Institute of Clinical Medicine, University of Eastern Finland , 70029 Kuopio ,","place":["Finland"]},{"name":"Department of Orthopedics, Kuopio University Hospital , 70029 Kuopio ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Tong","sequence":"additional","affiliation":[{"name":"Kuopio Musculoskeletal Research Unit (KMRU), Institute of Clinical Medicine, University of Eastern Finland , 70029 Kuopio ,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liisa","family":"Kerttula","sequence":"additional","affiliation":[{"name":"Diagnostic Center, Helsinki University Hospital and University of Helsinki , 00290 Helsinki,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4547-001X","authenticated-orcid":false,"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital , 00290 Helsinki ,","place":["Finland"]},{"name":"Research Program Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"Genetics Research Program, Folkh\u00e4lsan Research Center , 00014 Helsinki ,","place":["Finland"]},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet and Clinical Genetics, Karolinska University Hospital , 171 77 Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camilla","family":"Schalin-J\u00e4ntti","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, ENDO-ERN (European Reference Network on Rare Endocrine Conditions) , 00290 Helsinki 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