Mechanism of osteoclast generation through differentiation of precursor cells of the hematopoietic lineage induced by regulatory molecules. Calcitropic factors, such as vitamin D3, prostaglandin E2, interleukin‐1, interleukin‐2, tumor necrosis factor, and glucocorticoid induce receptor activator nuclear factor‐kappa ligand (RANKL) expression on osteoblasts. RANKL binding to the RANK expressed on hematopoietic progenitors activates a signal transduction cascade that leads to osteoclast differentiation in the presence of the survival factor colony‐stimulating factor 1.