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However, these drugs are often inconvenient to administer and are associated with side effects. Therefore, developing new treatments is of significant clinical importance. Puerarin (Pue) is a potential therapeutic agent for osteoporosis, but its poor solubility, low bioavailability, and instability limit its efficacy. In this study, we synthesized a tetrahedral framework nucleic acids(tFNAs)\u2013puerarin complex (TPC) by loading puerarin onto tFNAs. TPC demonstrates enhanced cellular uptake and stability, and shows superior osteogenic activity and anti\u2010osteoporosis effects compared to Pue alone, mediated through the FXR\/Runx2 pathway. In summary, we have developed a novel nanocomplex, TPC, with promising therapeutic potential for osteoporosis.<\/jats:p>","DOI":"10.1002\/adhm.202505921","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T09:36:12Z","timestamp":1774517772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tetrahedral Framework Nucleic Acid\u2013Puerarin Complex Alleviates Osteoporosis Through the FXR\/Runx2 Axis"],"prefix":"10.1002","volume":"15","author":[{"given":"Weifei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Spine Surgery Shenzhen Second People's Hospital Affiliated with the First Hospital of Shenzhen University  Shenzhen P. R. China"},{"name":"Department of Orthopedics Orthopedic Research Institute West China Hospital Sichuan University  Chengdu Sichuan P. R. 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