Bone remodeling is a highly complex and regulated process that ensures the functional and structural integrity of the skeleton by maintaining a balance between osteoclastic resorption and osteoblastic bone deposition. This process allows skeletal adaptation to biomechanical stresses and changes in the metabolic and hormonal environment while maintaining systemic mineral homeostasis. Imbalances in this equilibrium are the main mechanism underlying bone diseases, such as osteoporosis, which is characterized by progressive bone loss and deterioration of the skeletal microarchitecture. In particular estradiol deficiency, triggered by menopause, causes dramatic changes in the bone microenvironment and molecular mechanisms of skeletal remodeling, resulting in an increase in osteoclastic activity mediated by the RANK/RNKL/OPG pathway and favoring increased bone resorption.