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Current therapies, such as bisphosphonates and hormone replacement, have limitations and side effects, highlighting the need for safer alternatives. Flavonoids, bioactive compounds in traditional Chinese medicine, show promise due to their antioxidant, anti\u2010inflammatory, and estrogen\u2010mimetic properties. However, their complex interactions with bone metabolism pathways require systematic exploration. This review evaluates the regulatory effects of flavonoids on osteoporosis, focusing on their ability to enhance osteoblast\u2010mediated bone formation while inhibiting osteoclast\u2010driven resorption. We categorize major flavonoid subfamilies (flavones, flavonols, flavanones, and isoflavones) and detail their molecular mechanisms and signaling pathways contributing to clinical efficacy. Additionally, we address challenges related to flavonoid bioavailability, explore strategies for optimizing drug delivery, and highlight the integration of advanced technologies\u2014such as network pharmacology and artificial intelligence\u2014to uncover synergistic mechanisms in herbal formulations. These discussions provide a mechanistic framework supporting the role of flavonoids as multitarget modulators in osteoporosis therapy, offering insights for future pharmacological research and clinical applications.<\/jats:p>","DOI":"10.1002\/ptr.70229","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T02:00:28Z","timestamp":1769392828000},"page":"1512-1549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deciphering Multitarget Mechanisms of Phytochemical Flavonoids From Traditional Chinese Medicine: Emerging Insights Into Osteoporosis Therapeutics"],"prefix":"10.1002","volume":"40","author":[{"given":"Changxu","family":"Wang","sequence":"first","affiliation":[{"name":"College of Pharmacy, Hubei University of Chinese Medicine  Wuhan China"},{"name":"Department of Pharmacy Taihe Hospital, Hubei University of Medicine  Shiyan 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