MACROPHAGE ACTIVATION RESULTS IN BONE-RESORPTION

Monocytes or macrophages form important accessory cells in the regulat ion of bone metabolism and destruction. Cells of the mononuclear phago cyte lineage form the precursor cells of the osteoclasts, Soluble prod ucts produced by activated macrophages regulate progenitor cell prolif eration, recruitment, differentiation, and activity of osteoblasts and osteoclasts. After osteoclasts are removed from the resorption site, macrophages process bone surfaces and create a cement line before oste oblasts enter to form new bone. Although osteolysis associated with no rmal bone remodeling is seen as an osteoclast driven process, it may b e that in chronic inflammation macrophage activation and vascular dera ngements lead to low pH, local bone demineralization (acid attack), an d H+ mediated stimulation of the primary afferent nociceptive nerve fi bers (bone pain). Osteoclasts are not able to attach to demineralized bone or to osteoid surfaces. However, if macrophages degrade the demin eralized organic bone matrix, chemotactic factors and attachment sites for osteoclasts are produced. In such a scenario, the osteoclast-oste oblast mediated activation, resorption, and formation cycle would be s econdarily activated. Such events may play a role in the most common o rthopaedic problem related to macrophage activation, aseptic loosening of orthopaedic joint implants, which is secondary to a chronic foreig n body reaction and to micromovement.