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Improving the oxidative state is essential for the prevention and treatment of postmenopausal osteoporosis. There are three classes of antioxidant defense systems in the body to eliminate free radicals and peroxides including antioxidant substances, antioxidant enzymes, and repair enzymes. In our review, we demonstrated the mechanism of antioxidants and their effect on bone metabolism in detail. We concluded that glutathione\/oxidized glutathione (GSH\/GSSG) conversion involved the PI3K\/Akt-Nrf2\/HO-1 signaling pathway and that the antioxidant enzyme-mediated mitochondrial apoptosis pathway of osteoblasts was necessary for the development of postmenopausal osteoporosis. Since the current therapeutic effects of targeting bone cells are not significant, improving the systemic peroxidation state and then regulating bone homeostasis will be a new method for the treatment of postmenopausal osteoporosis.<\/jats:p>","DOI":"10.3389\/fphys.2022.840293","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T09:18:31Z","timestamp":1646299111000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Three Classes of Antioxidant Defense Systems and the Development of Postmenopausal Osteoporosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Keda","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangming","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchuan","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12072075","article-title":"Osteoprotective Activity and Metabolite Fingerprint via UPLC\/MS and GC\/MS of Lepidium sativum in Ovariectomized Rats.","volume":"12","author":"Abdallah","year":"2020","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","first-page":"560","DOI":"10.5483\/bmbrep.2008.41.8.5602\/18\/2022","article-title":"Phospholipase A(2), reactive oxygen species, and lipid peroxidation in CNS pathologies.","volume":"41","author":"Adibhatla","year":"2008","journal-title":"BMB Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.17219\/acem\/75689","article-title":"ALOX12 gene polymorphisms and serum selenium status in elderly osteoporotic patients.","volume":"27","author":"Al","year":"2018","journal-title":"Adv. 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