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Currently, therapeutic strategies for OP include antiresorptive and anabolic drugs. However, these treatments are often associated with adverse effects such as an increased risk of osteosarcoma, cardiovascular complications, and atypical fractures. This has led to an increased focus on alternative therapies, particularly those derived from traditional Chinese medicine (TCM). Natural coumarins (NC), which are naturally occurring compounds from various plants, have shown promise in modulating bone metabolism by controlling the function of osteoblasts and osteoclasts. Representative compounds such as osthole, psoralen, isopsoralen, and fraxin have demonstrated strong anti\u2010osteoporotic potential through distinct mechanisms: osthole enhances osteoblast differentiation via the Wnt\/\u03b2\u2010catenin and BMP2 pathways; psoralen activates estrogen receptor \u03b1 signaling to promote osteogenesis and inhibit osteoclastogenesis; isopsoralen alleviates oxidative stress to support osteogenic gene expression; and fraxin suppresses osteoclast formation by inhibiting ROS\/NF\u2010\u03baB while promoting osteoblast\u2010mediated bone formation through the Nrf2\/GPX4 pathway. Collectively, these findings highlight that NC exert multifaceted effects on bone metabolism by regulating classic pathways (OPG\/RANKL\/RANK, Wnt\/\u03b2\u2010catenin, BMP\/Smad, NF\u2010\u03baB, MAPK, and estrogen signaling) as well as cellular processes such as oxidative stress, autophagy, apoptosis, and adipogenesis. By synthesizing the current body of research, this review underscores the therapeutic potential of NC and encourages further innovation in OP treatment strategies.<\/jats:p>","DOI":"10.1002\/ptr.70319","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T03:42:02Z","timestamp":1774842122000},"page":"3369-3401","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Natural Coumarins: Unveiling Mechanisms for Osteoporosis Treatment"],"prefix":"10.1002","volume":"40","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy Anhui Medical University  Hefei People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicheng","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Anhui Medical University  Hefei People's Republic of 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