{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:39:48Z","timestamp":1793932788326,"version":"4.8.0"},"reference-count":174,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"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. Immunol."],"abstract":"<jats:p>Osteoporosis (OP) is a prevalent bone disease characterized by reduced bone mineral density (BMD) and compromised microstructure, leading to an increased risk of fractures and disability. With an aging global population, OP has become a significant public health issue, affecting over 200 million people worldwide. OP can be classified into primary (type I and type II) and secondary forms, with estrogen deficiency playing a critical role in postmenopausal OP. The pathophysiology of OP involves a complex interplay of factors, including cellular senescence, oxidative stress, inflammation, and hormonal imbalances. Bone homeostasis, maintained by the balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation, is regulated by various signaling pathways such as receptor activator of nuclear factor-\u03baB ligand\/receptor activator of nuclear factor-\u03baB\/osteoprotegerin (RANKL\/RANK\/OPG), interleukin-1\/tumor necrosis factor-\u03b1 (IL-1\/TNF-\u03b1), and Notch. Disruption of these pathways, along with oxidative stress and chronic inflammation, leads to bone loss. Estrogen deficiency enhances pro-inflammatory cytokine production, increases osteoclast differentiation, and accelerates bone resorption. Furthermore, cellular senescence and oxidative stress contribute to reduced osteoblast function and increased adipogenesis in bone marrow mesenchymal stem cells (BMSCs). Chronic inflammation and oxidative stress further exacerbate the imbalance in bone remodeling, promoting osteoclast activity and impairing osteogenesis. Understanding the roles of immune dysregulation, oxidative stress, and inflammation in osteoporosis progression is crucial for developing targeted therapeutic strategies. This review discusses the molecular mechanisms underlying inflammation and oxidative stress in OP, highlights current therapeutic approaches, and proposes future research directions aimed at improving the prevention and treatment of osteoporosis.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1611932","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T15:07:55Z","timestamp":1755011275000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":119,"title":["Oxidative stress and\u2002inflammation: roles\u2002in\u2002osteoporosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Jing","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensen","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangjie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.061113","article-title":"Incidence and economic burden of osteoporosis-related fractures in the United States 2005-2025","volume":"22","author":"Burge","year":"2007","journal-title":"J Bone Miner Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/550S15a","article-title":"Osteoporosis: staying strong","volume":"550","author":"Brown","year":"2017","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/1756-185x.12037","article-title":"The Malaysian clinical guidance on the management of postmenopausal osteoporosis 2012: A summary","volume":"16","author":"Yeap","year":"2013","journal-title":"Int J Rheum Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02925","article-title":"TNF-\u03b1 directly enhances osteocyte RANKL expression and promotes osteoclast formation","volume":"10","author":"Marahleh","year":"2019","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/0022034519854704","article-title":"The function of wnt ligands on osteocyte and bone remodeling","volume":"98","author":"Du","year":"2019","journal-title":"J Dent Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.semcdb.2021.05.014","article-title":"Interaction between bone and immune cells: Implications for postmenopausal osteoporosis","volume":"123","author":"Fischer","year":"2022","journal-title":"Semin Cell Dev Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.bone.2015.05.034","article-title":"Bone marrow ablation demonstrates that estrogen plays an important role in osteogenesis and bone turnover via an antioxidative mechanism","volume":"79","author":"Shi","year":"2015","journal-title":"Bone"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1159\/000443531","article-title":"Upregulated cellular expression of IL-17 by CD4+ T-cells in osteoporotic postmenopausal women","volume":"68","author":"Zhao","year":"2016","journal-title":"Ann Nutr Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.05.015","article-title":"Multi-mechanisms are involved in reactive oxygen species regulation of mTORC1 signaling","volume":"22","author":"Li","year":"2010","journal-title":"Cell Signal"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1177\/0022034520983245","article-title":"Hyperlipidemia impairs osseointegration via the ROS\/wnt\/\u03b2-catenin pathway","volume":"100","author":"Wang","year":"2021","journal-title":"J Dent. 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