New knowledge on the origin, function and fate of osteoclasts.

The most recent findings on the origin, life-span and fate of the osteoclast can be summarized as follows. Osteoclasts originate from progenitor, mononuclear, lymphoid cells which reach the bone surface through the bloodstream. Osteoclasts resorb bone by secreting lysosomal enzymes and procollagenase in the osteoclast-bone interspace. The organic components of the matrix (first interfibrillary substance, then collagen fibrils) are digested in the extracellular space. Dislodged crystals and residual organic constituents are then phagocytosed and collected in cytoplasmic vacuoles where they are completely solubilized. The ruffled border and the adjacent "clear" zone constitute the resorbing apparatus, whose development is roughly proportional to osteoclast activity. Osteoclast nuclei are continuously incorporated and shed, so that individual cells are continuously renewed. This makes the life-span of the osteoclast extremely difficult to determine. The life of each individual osteoclast might theoretically continue as long as the stimulus to resorption persists and sufficient bone matrix is available. Primary abnormalities of the osteoclasts can induce pathologic skeletal changes, as in the case of osteopetrosis and Paget's disease of bone. Conversely, skeletal abnormalities may damage osteoclasts, as in the case of lead intoxication. When this happens, osteoclasts are essentially characterized by an underdeveloped ruffled border, pyknotic nuclei, detachment from the bone matrix and, finally, shrinkage and fragmentation. It is not yet known whether these changes only occur in pathologic conditions, or whether they are the alterations which lead senescent osteoclasts to death even in normal bone.