The Potential Mechanism of Soy Isoflavones in Treating Osteoporosis: Focusing on Bone Metabolism and Oxidative Stress

ABSTRACT Osteoporosis is divided into primary and secondary types. Primary osteoporosis may result from estrogen deficiency in postmenopausal women, imbalanced bone remodeling in the elderly, or imbalanced adolescent—type bone development. Secondary osteoporosis can be caused by factors like long—term glucocorticoid treatment, chronic kidney disease (CKD), estrogen deprivation, oxidative stress, diabetes, and obesity. This review focuses on the therapeutic potential of soy isoflavones for osteoporosis. At the cellular level, soy isoflavones, as natural plant extracts and phytoestrogens, are crucial for osteoblastogenesis and differentiation, osteoclastogenesis, osteoclast mineralization, and bone marrow mesenchymal stromal cell differentiation. They also maintain calcium homeostasis by regulating extracellular calcium and vitamin D levels. In terms of oxidative stress, soy isoflavones mitigate it in the endoplasmic reticulum and mitochondria, thus regulating cellular senescence, autophagy, and bone remodeling processes. Moreover, soy isoflavones can relieve symptoms related to CKD and inhibit glucocorticoid secretion, which directly or indirectly benefits the treatment of osteoporosis. Overall, soy isoflavones have the potential to treat osteoporosis by enhancing bone health, regulating metabolism, and alleviating oxidative stress. Future research should explore the potential of soy isoflavones as phytoestrogens for treating osteoporosis. This exploration should focus on clarifying the safety, identifying potential side effects, determining the optimal dosage regimen, and developing strategies to mitigate any adverse reactions. In addition, further large‐scale, multicenter human clinical trials are necessary to accurately evaluate the actual therapeutic effect of soy isoflavones on osteoporosis.