Bone—From macrophage to osteoclast and osteolytic diseases

Osteoclasts are giant multinucleated cells derived from myeloid precursor cells in the bone marrow and have a unique bone-destroying capacity. Osteoclasts are essential for homeostatic bone remodeling in health, and the receptor activator of nuclear factor-kappa B ligand (RANKL) is the critical cytokine that induces osteoclastogenesis. However, several factors can disrupt this essential physiological process, including menopause-associated hormonal changes, age-related factors, trauma, drugs, and infectious diseases, which lead to the development of various bone disorders in both women and men. Here we discuss the historical background and the recent advances in understanding osteoclast differentiation by focusing on the RANKL signaling. Also, we review the major osteolytic diseases emphasizing our current knowledge of the underlying pathophysiological mechanisms.