REVIEW article
Front. Aging
Sec. Musculoskeletal Aging
Wnt16: a new potential therapeutic target for osteoporotic non-vertebral fracture treatment
Provisionally accepted
Tian Peng Chen
Gongtao Jiang*- Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, China
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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 nonvertebral 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/β-catenin pathways) and osteoclasts (via OPG-dependent/independent NF-κB 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.
Keywords: BMD, Bone, Non-vertebral fracture, Osteoporosis, Wnt16
Received: 16 Dec 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Chen and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gongtao Jiang
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