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Macrophage Activation Results in Bone Resorption

Lassus, Jan; Salo, Jari; Jiranek, William, A; Santavirta, Seppo; Nevalainen, Juha; Matucci-Cerinic, Marco††; Horák, Pavel; Konttinen, Yrjö§¶#

Clinical Orthopaedics and Related Research: July 1998 - Volume 352 - Issue - p 7–15

Monocytes or macrophages form important accessory cells in the regulation of bone metabolism and destruction. Cells of the mononuclear phagocyte lineage form the precursor cells of the osteoclasts. Soluble products produced by activated macrophages regulate progenitor cell proliferation, 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 osteoblasts enter to form new bone. Although osteolysis associated with normal bone remodeling is seen as an osteoclast driven process, it may be that in chronic inflammation macrophage activation and vascular derangements lead to low pH, local bone demineralization (acid attack), and H+ mediated stimulation of the primary afferent nociceptive nerve fibers (bone pain). Osteoclasts are not able to attach to demineralized bone or to osteoid surfaces. However, if macrophages degrade the demineralized organic bone matrix, chemotactic factors and attachment sites for osteoclasts are produced. In such a scenario, the osteoclast-osteoblast mediated activation, resorption, and formation cycle would be secondarily activated. Such events may play a role in the most common orthopaedic problem related to macrophage activation, aseptic loosening of orthopaedic joint implants, which is secondary to a chronic foreign body reaction and to micromovement.

Department of Orthopaedics and Traumatology Medicine, Helsinki University Central Hospital, Helsinki, Finland; Tuckahoe Orthopaedic Associates Limited, Tuckahoe, VA

National Agency for Medicines, Medical Device Centre, Helsinki, Finland

††Institute of Clinical Medicine IV, University of Florence, Firenze, Italy

§Institute of Biomedicine, Department of Anatomy, University of Helsinki, Helsinki, Finland

Department of Rheumatology, Olomouc University, Olomouc, Czech Republic

#ORTON Research Institute, Invalid Foundation, Helsinki, Finland.

© Lippincott-Raven Publishers.