Abstract 47

Receptor activator of nuclear factor kappaB (RANK) and tumour necrosis factor-_ (TNF- _) expression in tissues obtained from sites of peri-implant osteolysis characterised by CT.

Holding C.A.(1), Shrestha K.R.(2), Dharmapatni K.(1), Stamenkov R.(2), Neale S.D.(2), Findlay D.M.(2), Atkins G.J. (2) Howie D.W (2) and Haynes D.R.(1)

(1) Department of Pathology, Adelaide University, South Australia, 5005, Australia.
(2) Department of Orthopaedics and Trauma, Adelaide University, South Australia, 5000, Australia.

RANK and TNF-a are key factors regulating bone resorption in disease. RANK is a crucial factor that induces osteoclastogenesis. TNF-a stimulates both the inflammatory response and osteoclastogenesis either in synergy with RANK activation or alone. The aim of this study was to investigate the expression of RANK and TNF-a in tissues from sites of osteolysis identified from CT scans of patients undergoing total hip replacement. High-resolution spiral multislice CT, with a metal artefact suppression protocol was used to select tissue and to measure the volume of osteolytic lesions around titanium cementless acetabular and femoral components of total hip arthroplasties. Immunohistochemical analysis of formalin fixed sections from 8 patients undergoing revision of total hip prosthesis was performed using monoclonal antibodies directed against RANK and TNF-a (R&D Systems). Control tissue consisted of synovial tissue samples taken from patients with osteoarthritis. Sections were evaluated by light microscopy and polarised light was used to detect polyethylene particles. Both RANK and TNF-a were strongly expressed in revision tissues adjacent to osteolytic lesions and were associated with large multinucleated osteoclast-like cells, and macrophages. Control tissue stained very weakly for both RANK and TNF-a. Under polarised light, large numbers of polyethylene particles were distinctly visible within the RANK expressing multinucleated osteoclast-like cells. This study demonstrates the expression of both RANK and TNF-a is elevated in tissues from sites of peri-implant osteolysis, and that these molecules are associated with large multinucleated cells that had phagocytosed large numbers of small polyethylene particles, implicating polyethylene wear as a cause of peri-prosthetic osteolysis.

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