The Osteoclast: Friend or Foe?

Abstract

Bone is a dynamic organ constantly remodeled to support calcium homeostasis and structural needs. The osteoclast is the cell responsible for removing both the organic and inorganic components of bone. It is derived from hematopoietic progenitors in the macrophage lineage and differentiates in response to the tumor necrosis factor family cytokine receptor activator of NFκB ligand. αvβ3 integrin mediates cell adhesion necessary for polarization and formation of an isolated, acidified resorptive microenvironment. Defects in osteoclast function, whether genetic or iatrogenic, may increase bone mass but lead to poor bone quality and a high fracture risk. Pathological stimulation of osteoclast formation and resorption occurs in postmenopausal osteoporosis, inflammatory arthritis, and metastasis of tumors to bone. In these diseases, osteoclast activity causes bone loss that leads to pain, deformity, and fracture. Thus, osteoclasts are critical for normal bone function, but their activity must be controlled.