Deciphering epigenetic regulation in postmenopausal osteoporosis: Current and future perspectives

Abstract Postmenopausal osteoporosis is the most prevalent form of osteoporosis, affecting approximately 33% of postmenopausal women globally and representing a major cause of age‐related disability and mortality. The pathological mechanism involves disrupted bone homeostasis, where osteoclast‐mediated bone resorption exceeds osteoblast‐mediated bone formation due to estrogen deficiency and altered cytokine regulation. Postmenopausal osteoporosis pathogenesis, bone metabolism, drug resistance, and fracture susceptibility are closely associated with epigenetic modifications, particularly noncoding RNA regulation. With the continuous advancement of epigenetic research, noncoding RNAs have gradually become important tools for understanding bone remodeling mechanisms and studying the reciprocal interactions between genetic regulation and bone metabolism. In this perspective, the significant roles of microRNAs, long noncoding RNAs and circular RNAs in postmenopausal osteoporosis are thoroughly expounded. The advantages and limitations of typical noncoding RNAs as diagnostic biomarkers and therapeutic targets are summarized and discussed. Moreover, based on the epigenetic modification patterns and regulatory networks observed in bone diseases, the future development directions of noncoding RNA research in postmenopausal osteoporosis are emphasized, aiming to provide references for basic research and clinical precise treatment.