{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T07:36:14Z","timestamp":1773041774820,"version":"3.50.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>Osteoporotic non-vertebral fractures are a major clinical burden, with cortical bone impairment being a key pathogenic factor often overlooked in traditional treatments. This review aims to synthesize current evidence on the role of Wnt16 (a non-canonical Wnt ligand) in regulating cortical bone and its potential as a therapeutic target for osteoporotic non-vertebral fractures. We systematically review literature on Wnt16 in senile, postmenopausal, and glucocorticoid-induced osteoporosis, focusing on its mechanisms of action: (1) regulating bone mineral density via genetic associations with GWAS-identified loci; (2) reducing cortical bone porosity and increasing thickness; (3) dual regulation of osteoblasts (via JNK\/\u03b2-catenin pathways) and osteoclasts (via OPG-dependent\/independent NF-\u03baB pathways). Wnt16 has been shown to improve bone density and reduce non-vertebral fracture risk in preclinical models, though conflicting findings exist regarding its full compensation for glucocorticoid-induced bone loss. We conclude that Wnt16 is a promising target for non-vertebral fracture prevention, with Notum inhibitors emerging as potential therapeutic agents. This review provides a comprehensive framework for future clinical and translational research.<\/jats:p>","DOI":"10.3389\/fragi.2026.1768566","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:46:14Z","timestamp":1773038774000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Wnt16: a new potential therapeutic target for osteoporotic non-vertebral fracture treatment"],"prefix":"10.3389","volume":"7","author":[{"given":"Chen","family":"Tianpeng","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Nanchang Hongdu Hospital of Traditional Chinese Medicine Affiliated to Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Qishui","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Nanchang Hongdu Hospital of Traditional Chinese Medicine Affiliated to Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Fo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Nanchang Hongdu Hospital of Traditional Chinese Medicine Affiliated to Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wu","family":"Mingjun","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Nanchang Hongdu Hospital of Traditional Chinese Medicine Affiliated to Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hu","family":"Haibo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Nanchang Hongdu Hospital of Traditional Chinese Medicine Affiliated to Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Jiuchu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Nanchang Hongdu Hospital of Traditional Chinese Medicine Affiliated to Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi","family":"Xiaolin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Gongtao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Nanchang Hongdu Hospital of Traditional Chinese Medicine Affiliated to Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e10084","DOI":"10.1002\/jbm4.10084","article-title":"Overexpression of Wnt16 does not prevent cortical bone loss due to glucocorticoid treatment in mice","volume":"3","author":"Alam","year":"2018","journal-title":"JBMR Plus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1002\/jbmr.3247","article-title":"Osteocyte mechanotransduction: the role of Wnt signaling in maintaining skeletal homeostasis","volume":"32","author":"Almeida","year":"2017","journal-title":"J. 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