Pathological bone resorption in rheumatic diseases

Abstract

Bone resorption in a common feature of rheumatoid and other inflammatory joint conditions. This osteolysis is effected by osteoclasts, highly specialised multinucleated cells which are formed by fusion of mononuclear phagocyte precursors of haematopoietic origin. It has been shown that human osteoclast precursors circulate in the monocyte fraction of peripheral blood and are present in the macrophage population of normal and pathological tissues. The cellular and humoral requirements for human monocyte/macrophage-osteoclast differentiation are the presence of bone-derived stromal cells, which express the membrane-bound protein termed osteoclast differentiation factor or osteoprotegerin ligand (ODF/OPGL), and macrophage-colony stimulating factor (M-CSF). Macrophages form a major component of the inflammatory infiltrate in the rheumatoid synovium and in other conditions such as PVNS and aseptic loosening. Local factors (e.g. cytokines and growth factors) produced in this microenvironment act to stimulate not only osteoclast activity but also osteoclast formation. In the context of RA and other joint conditions in which osteolysis occurs, pathological bone resorption should be regarded as a function not only of osteoclast activity but also of osteoclast formation from mononuclear phagocyte precursors.