Osteoclasts Have Multiple Roles in Bone in Addition to Bone Resorption

Osteoclasts are the cells that degrade bone to initiate normal bone remodeling and mediate bone loss in pathologic conditions by increasing their resorptive activity. They are derived from precursors in the myeloid/ monocyte lineage that circulate in the blood after their formation in the bone marrow. These osteoclast precursors (OCPs) are attracted to sites on bone surfaces destined for resorption and fuse with one another to form the multinucleated cells that resorb calcified matrixes under the influence of osteoblastic cells in bone marrow. Recent studies have identified functions for OCPs and osteoclasts in and around bone other than bone resorption. For example, they regulate the differentiation of osteoblast precursors and the movement of hematopoietic stem cells from the bone marrow to the bloodstream; they participate in immune responses, and secrete cytokines that can affect their own functions and those of other cells in inflammatory and neoplastic processes affecting bone. Here, we review these findings, which define new roles for osteoclasts and OCPs in the growing field of osteoimmunology and in common pathologic conditions in which bone resorption is increased.