Osteoklastresorption

Osteoklastresorption, or osteoclast-mediated bone resorption, is the process by which osteoclasts dissolve mineralized bone matrix during bone remodeling. Osteoclasts are large, multinucleated cells of the monocyte–macrophage lineage that attach to bone surfaces at a sealing zone and form a specialized apical membrane called the ruffled border to create a resorption lacuna.

Resorption begins with adhesion to the mineralized surface, followed by acidification and enzymatic degradation. Proton pumps (V-ATPase) and chloride channels acidify the lacuna, dissolving hydroxyapatite, while proteolytic enzymes such as cathepsin K and tartrate-resistant acid phosphatase digest organic matrix proteins, particularly type I collagen. The resorption pit, or lacuna, is then sealed and later refilled with new bone as osteoblasts deposit osteoid. The ruffled border and sealing zone are essential for efficient mineral dissolution and matrix breakdown.

Resorption is tightly regulated by signaling from osteoblast lineage cells. RANKL, produced by osteoblasts and stromal cells, binds to RANK on osteoclast precursors to promote differentiation and activity; osteoprotegerin (OPG) acts as a decoy receptor to limit RANKL signaling. Hormonal and mechanical factors, such as parathyroid hormone, estrogens, and mechanical loading, modulate this pathway; calcitonin inhibits osteoclast activity. Resorption is coupled to bone formation by osteoblasts, ensuring replacement of old bone with new tissue.

Clinical relevance: balanced osteoklast resorption is essential for skeletal integrity; excessive resorption contributes to osteoporosis and osteolytic cancers, while deficient resorption causes osteopetrosis. Treatments that reduce resorption include bisphosphonates and denosumab (a RANKL inhibitor), as well as calcitonin in some settings.

Laboratory assessment may use bone turnover markers, histology, or in vitro assays measuring resorption pits on dentin or bone slices to study osteoclast function.