Osteoclasts

Osteoclasts are large, multinucleated cells responsible for bone resorption, playing a central role in bone remodeling. They originate from hematopoietic precursors of the monocyte–macrophage lineage and form by the fusion of several mononuclear cells. When attached to the bone surface, osteoclasts create a sealed resorption lacuna and develop a specialized ruffled border that interfaces with the bone matrix, allowing targeted degradation of mineral and organic components.

In the resorption process, osteoclasts acidify the local environment and secrete proteolytic enzymes. Proton pumps and carbonic anhydrase generate an acidic microenvironment that dissolves hydroxyapatite, while enzymes such as cathepsin K and matrix metalloproteinases break down the organic matrix. The activity occurs at a site known as the Howship’s lacuna, and the resorbed material is carried away by vesicles and lacunar fluid.

Formation and activity are tightly regulated by signals from osteoblasts and osteocytes. RANKL, produced by osteoblast lineage cells, binds to RANK on osteoclast precursors to promote differentiation; M-CSF supports precursor survival. Osteoprotegerin (OPG) acts as a decoy receptor for RANKL, inhibiting osteoclastogenesis. Hormonal factors such as estrogen and inflammatory cytokines influence resorption, with estrogen deficiency generally increasing osteoclast activity.

Clinical relevance includes disorders of imbalanced resorption. Excessive osteoclast activity contributes to osteoporosis and certain cancers with bone involvement, whereas reduced resorption characterizes osteopetrosis. Therapies such as bisphosphonates and RANKL inhibitors (for example, denosumab) target osteoclast function to modulate bone remodeling.