osteoclasti

Osteoclasti (osteoclasts in English) are large, multinucleated cells specialized for bone resorption and are essential to the bone remodeling cycle. They originate from hematopoietic stem cells of the monocyte/macrophage lineage and form by the fusion of precursors under the influence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). Their differentiation and activity are regulated by the RANK/RANKL/osteoprotegerin (OPG) axis, with OPG acting as a decoy receptor to limit osteoclast formation.

In resorption, osteoclasts attach to the bone surface, creating a sealing zone and a ruffled border. They secrete protons to acidify the resorption lacuna and release proteolytic enzymes such as cathepsin K and matrix metalloproteinases to dissolve hydroxyapatite and degrade collagen. The resulting resorption pit is known as a Howship’s lacuna. After resorption, osteoclasts may undergo apoptosis or be replaced by osteoblasts that form new bone.

This activity is tightly balanced with osteoblast-mediated bone formation to maintain skeletal strength. Hormonal and mechanical factors modulate osteoclasts: parathyroid hormone (PTH) and low estrogen levels tend to enhance resorption, while calcitonin and adequate mechanical loading can suppress it.

Clinical relevance includes disorders of bone loss and remodeling. Excess osteoclast activity contributes to osteoporosis and osteolysis in Paget’s disease or metastases; insufficient activity can lead to osteopetrosis. Treatments that inhibit osteoclasts, such as bisphosphonates and denosumab (RANKL inhibitor), are used to manage these conditions. Markers of osteoclast activity include tartrate-resistant acid phosphatase (TRAP) and bone turnover products like CTX.