Human osteoclast ontogeny and pathological bone resorption

Monocytes and macrophages are capable of degrading both the mineral and org anic components of bone and are known to secrete local factors which stimul ate host osteoclastic bone resorption. Recent studies have shown that monoc ytes and macrophages, including those isolated from neoplastic and inflamma tory lesions, can also be induced to differentiate into cells that show all the cytochemical and functional characteristics of mature osteoclasts, inc luding lacunar bone resorption. Monocyte/macrophage-osteoclast differentiat ion occurs in the presence of osteoblasts/bone stromal cells (which express osteoclast differentiation factor) and macrophage-colony stimulating facto r and is inhibited by osteoprotegerin. Various systemic hormones and local factors (eg cytokines, growth factors, prostaglandins) modulate osteoclast formation by controlling these cellular and humoral elements. Various patho logical lesions of bone and joint (eg carcinomatous metastases, arthritis, aseptic loosening) are associated with osteolysis. These lesions generally contain a chronic inflammatory infiltrate in which macrophages form a signi ficant fraction. One cellular mechanism whereby pathological bone resorptio n may be effected is through generation of increased numbers of bone-resorb ing osteoclasts from macrophages. Production of humoral factors which stimu late mononuclear phagocyte-osteoclast differentiation and osteoclast activi ty is also likely to influence the extent of pathological bone resorption.