{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:24:32Z","timestamp":1787225072362,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:p>Osteoporosis is a systemic skeletal disease characterized by low bone mass, deterioration of bone microarchitecture, and increased fracture risk, which imposes a heavy burden on global public health, especially in postmenopausal women and the elderly. The gut-bone axis, a bidirectional regulatory network between the gut microbiota and bone metabolism, has emerged as a novel therapeutic target for osteoporosis. Indole derivatives, a class of bioactive compounds derived from tryptophan metabolism by gut microbiota or plant secondary metabolism, have attracted increasing attention due to their extensive biological activities, including anti-inflammatory, antioxidant, and metabolic regulatory effects. Accumulating evidence indicates that indole derivatives can regulate bone homeostasis through the gut-bone axis, providing a new strategy for the prevention and treatment of osteoporosis. This review systematically summarizes the types of indole derivative, elaborates their molecular mechanisms in the treatment of osteoporosis via the gut-bone axis (including regulating gut microbiota composition, maintaining intestinal barrier integrity, modulating immune-inflammatory responses, and mediating key signaling pathways), and discusses the current translational progress, existing challenges, and future prospects. This review aims to provide a comprehensive theoretical basis for the clinical application of indole derivatives in osteoporosis treatment and the development of novel targeted drugs.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1845772","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:35:26Z","timestamp":1787222126000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Indole derivatives intervene osteoporosis via gut-bone axis"],"prefix":"10.3389","volume":"16","author":[{"given":"Wendong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Engineering Mechanics, Dalian University of Technology","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1360054","article-title":"Apigenin and rutaecarpine reduce the burden of cellular senescence in bone marrow stromal stem cells","volume":"15","author":"Ali","year":"2024","journal-title":"Front. 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