{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:07:27Z","timestamp":1789546047320,"version":"build-2803163510"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoporosis (OP) is characterized by bone coupling imbalance\u2014insufficient osteoblast-mediated formation and excessive osteoclast-mediated resorption. Among multiple signaling networks involved in bone remodeling, the canonical Wnt\/beta-catenin pathway and the osteoprotegerin\/receptor activator of nuclear factor-kappaB ligand\/receptor activator of nuclear factor-kappaB axis, namely the OPG\/RANKL\/RANK axis, were selected because they represent two central and mutually interacting regulatory systems governing osteoblast differentiation and osteoclastogenesis. Traditional Chinese Medicine (TCM) offers multi-target potential for regulating bone homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This narrative review examines TCM interventions targeting Wnt\/\u03b2-catenin and OPG\/RANKL\/RANK pathways in OP, emphasizing bone coupling and pathological subtype differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Structured literature searches (PubMed, Web of Science Core Collection, CNKI, Wanfang, cqVIP; 2000\u20132025) with OCEBM\/SYRCLE evidence grading were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TCM suggests bidirectional bone coupling regulation through multi-target mechanisms, but evidence remains predominantly preclinical (Levels 4\u20135). Pharmacokinetic barriers (low oral bioavailability of icariin, berberine), safety concerns (Xianling Gubao hepatotoxicity), and lack of fracture-endpoint RCTs limit clinical translation. Future research should prioritize target-engagement biomarkers, bone-targeted delivery, and adequately powered RCTs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1924175","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:47:30Z","timestamp":1789544850000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Traditional Chinese medicine regulating Wnt\/\u03b2-catenin and OPG\/RANKL\/RANK pathways in osteoporosis: a narrative review based on bone coupling and pathological subtype differences"],"prefix":"10.3389","volume":"13","author":[{"given":"Shi-Lei","family":"Song","sequence":"first","affiliation":[{"name":"Joint Surgery Department, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Min","family":"Li","sequence":"additional","affiliation":[{"name":"Joint Surgery Department, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Yi","family":"Feng","sequence":"additional","affiliation":[{"name":"Joint Surgery Department, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Ming","family":"Lu","sequence":"additional","affiliation":[{"name":"Joint Surgery Department, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1456796","DOI":"10.3389\/fphar.2024.1456796","article-title":"Osteoporosis treatment: current drugs and future developments","volume":"15","author":"Chen","year":"2024","journal-title":"Front Pharmacol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"WNT Signaling in bone homeostasis and disease: from human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s00774-020-01162-6","article-title":"Osteoclast differentiation by RANKL and OPG signaling pathways","volume":"39","author":"Udagawa","year":"2021","journal-title":"J Bone Miner 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