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To improve the shortcomings of the current clinical osteoporosis treatment drugs, several studies have designed a multitude of nanomedicines to optimize traditional drugs based on the TOP\u2013DOWN design. Fascinating nanomedicine designs are breathing vitality into traditional osteoporosis drugs. However, considering the unique pathological characteristics of osteoporosis and clinical treatment needs, we should also pay attention to the problems outside the spotlight. Here, we reviewed the current clinical osteoporosis treatment drugs, summarized their limitations, and generalized the nanomedicines designed based on the TOP\u2013DOWN strategy for the mentioned deficiencies. In addition, we explored the issues outside the spotlight of the nanomedicine design for the treatment of osteoporosis because of the gap between laboratory design strategy and clinical demands and then determined the rational design of nanomedicines for osteoporosis.<\/jats:p>","DOI":"10.1177\/03000605251391597","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T23:55:36Z","timestamp":1765410936000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["In and outside the spotlight: Nanomedicine in the treatment of osteoporosis"],"prefix":"10.1177","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1760-2254","authenticated-orcid":false,"given":"Hao","family":"Qu","sequence":"first","affiliation":[{"name":"Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9922-3340","authenticated-orcid":false,"given":"Wenkang","family":"Luan","sequence":"additional","affiliation":[{"name":"Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"He","sequence":"additional","affiliation":[{"name":"Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001980070064"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650100202"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(93)90218-E"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001980050224"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2012.04.006"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2307353"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1365.035"},{"key":"e_1_3_6_9_2","first-page":"1017","article-title":"Osteoporosis: pathophysiology and therapeutic options","volume":"19","author":"Foger-Samwald U","year":"2020","unstructured":"Foger-Samwald U, Dovjak P, Azizi-Semrad U, et\u00a0al. 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