title: Assessment of the role of GM-CSF in the cellular transformation and the development of erosive lesions around orthopaedic implants.
abstract: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor with a regulatory effect on the transformation of immature macrophages into multinucleated giant cells (MNGC) that exhibit phenotypic and functional characteristics of osteoclasts (OC). The authors analyzed the bone implant interface membranes harvested from 15 patients with failed total joint replacements for the production and tissue distribution of GM-CSF and interleukin-1 (IL-1). Immunohistology and liquid culture were employed to assess the contribution of these factors in the recruitment of macrophages and the development of bone resorbing MNGC at these sites. This process has been implicated in osteoclastic bone resorption, bone, and bone marrow necrosis adjacent to orthopaedic implants. Histologic assessment of the interface indicated the presence of granuloma and a variable number of MNGC in 11 cases. Four cases showed sites of intramembranous formation of osteoid and mineralized bone that was accompanied by normal bone marrow in two cases. Granulocyte-macrophage colony stimulating factor was expressed by a distinct subset of phagocytic macrophages in the lining layer on the implant side. interleukin-1-positive cells outnumbered those stained for GM-CSF. Stimulation of cultured cells with prosthetic metal particulate material showed marked similarity in the expression of these cytokines to cultures treated with lipopolysaccharide (LPS) or phytohemagglutinin (PHA). The induction of GM-CSF production in the lining layer where small MNGC develop indicates that these cells differentiate locally following the phagocytosis of particulate wear debris. In conclusion, GM-CSF promotes the proliferation and early stages of fusion and development of MNGC responsible for osteolysis at these sites. These results also highlight the capacity of the interface to display both osteogenic and inflammatory characteristics. Collectively, the findings suggest that the local bone marrow could participate in the development of the interface as a source of myeloid cells in addition to the capacity of marrow stroma to generate various osteogenic cells essential for the ingrowth of bone into prosthetic implants.
authors.affiliation: Department of Histopathology, Royal Free Hospital School of Medicine, Hampstead, London, England.
authors.forename: N
authors.initials: N
authors.lastname: Al-Saffar
authors.forename: H A
authors.initials: HA
authors.lastname: Khwaja
authors.forename: Y
authors.initials: Y
authors.lastname: Kadoya
authors.forename: P A
authors.initials: PA
authors.lastname: Revell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000032:analysis; D001862:Bone Resorption / Q000503:physiopathology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007595:Joint Prosthesis / Q000009:adverse effects*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016348:Osseointegration / Q000502:physiology; D011475:Prosthesis Failure; D011859:Radiography
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000469:Alkaline Phosphatase