Postmenopausal osteoporosis (PMO) is a common metabolic bone disorder in women. Estrogen deficiency and disturbed calcium-phosphorus metabolism are the main causes. Patients face higher fracture risk and reduced quality of life. Current drug treatments include bisphosphonates, selective estrogen receptor modulators (SERMs), parathyroid hormone (PTH) analogs, and denosumab. But single-drug therapy often falls short in improving both bone mass and bone quality. The combination of estrogen and active vitamin D has drawn more interest lately. These two agents work through different but complementary pathways: estrogen suppresses bone resorption, while active vitamin D promotes calcium absorption and bone mineralization. Some studies show this combination can increase bone density. However, long-term safety, patient selection, and adherence remain unresolved. Meanwhile, the continuous development of new technologies such as artificial intelligence (AI), big data analysis, and mesenchymal stem cells (MSCs) has also provided new ideas for the risk assessment and individualized intervention of PMO. This article reviews the research progress of estrogen combined with active vitamin D in the treatment of PMO and discusses the optimization direction of drug combination strategies.