<p>Osteoporosis, a debilitating condition characterized by reduced bone mass and increased fracture risk, is notably influenced by estrogen deficiency and glucocorticoid treatment. This comprehensive review elucidates the molecular mechanisms underpinning estrogen deficiency-related osteoporosis (EDOP) and glucocorticoid-induced osteoporosis (GIOP). The role of estrogen in bone metabolism is critically examined, highlighting its regulatory effects on bone turnover and formation through various signaling pathways. Conversely, this review explores how glucocorticoids disrupt bone homeostasis, focusing on their impact on osteoclast and osteoblast function and the subsequent alteration of bone remodeling processes. The pathogenesis of both conditions is intertwined, with estrogen receptor signaling pathways and the role of inflammatory cytokines being pivotal in driving bone loss. A detailed analysis of pathogenetic and risk factors associated with EDOP and GIOP is presented, including lifestyle and genetic factors contributing to disease progression. Modern therapeutic approaches emphasize pharmacologic, non-pharmacologic, and herbal treatments for managing EDOP and GIOP. In summary, current therapeutic strategies highlight the efficacy and the safety of various interventions. This review concludes with future directions for research, suggesting a need for novel treatment modalities and a deeper understanding of the underlying mechanisms of osteoporosis. By addressing the multifaceted nature of EDOP and GIOP, this work aims to provide insights into developing targeted therapeutic strategies and improving patient outcomes in osteoporosis management.</p>