Postmenopausal osteoporosis and vascular calcification: The estrogen regulation network and calcification paradox

Abstract The decline in estrogen levels in postmenopausal women is a major risk factor for the high prevalence of osteoporosis and vascular calcification in this population. Estrogen deficiency leads to an imbalance in the RANKL/OPG ratio, abnormalities in the Wnt/β-catenin pathway, and disruptions in bone morphogenetic protein (BMP) signaling, thereby inducing osteoporosis and vascular calcification. Moreover, estrogen deficiency affects calcium and phosphorus metabolism and induces the release of extracellular vesicles from the aging bone matrix, which mediate interactions between bone and vascular tissues and promote the occurrence of the "calcification paradox." The epigenetic regulation of estrogen receptors, including DNA methylation, histone modification, and miRNA activity, exerts different effects in bone and vascular tissues, underscoring the complexity of estrogen regulation. Future research should focus on the precise regulation of estrogen receptor subtypes and tissue-specific epigenetic modulation mechanisms to develop effective therapeutic strategies for osteoporosis and vascular calcification in postmenopausal women.