Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/23232
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Type: Journal article
Title: The correlation of RANK, RANKL and TNFα expression with bone loss volume and polyethylene wear debris around hip implants
Other Titles: The correlation of RANK, RANKL and TNFalpha expression with bone loss volume and polyethylene wear debris around hip implants
Author: Holding, C.
Findlay, D.
Stamenkov, R.
Neale, S.
Lucas, H.
Dharmapatni, A.
Callary, S.
Shrestha, K.
Atkins, G.
Howie, D.
Haynes, D.
Citation: Biomaterials, 2006; 27(30):5212-5219
Publisher: Elsevier Sci Ltd
Issue Date: 2006
ISSN: 0142-9612
1878-5905
Statement of
Responsibility: 
Christopher A. Holding, David M. Findlay, Roumen Stamenkov, Susan D. Neale, Helen Lucas, A.S.S.K. Dharmapatni, Stuart A. Callary, Kush R. Shrestha, Gerald J. Atkins, Donald W. Howie, and David R. Haynes
Abstract: This study investigates receptor activator NF-κB (RANK), RANK ligand (RANKL) and tumour necrosis factor (TNFα), key factors regulating bone turnover, present in the tissues near peri-prosthetic osteolysis. Tissue was obtained from zones of peri-prosthetic osteolysis from 11 patients undergoing revision of total hip prostheses, analysed preoperatively by high-resolution spiral multislice CT using a metal artefact suppression protocol. Synovial tissue from 10 patients with osteoarthritis undergoing primary hip replacement was used as control tissue. Immunohistochemical analysis of formalin fixed tissue sections demonstrated that RANK, RANKL and TNFα were strongly expressed by large multinucleated cells containing polyethylene wear debris in revision tissues. Control tissue stained weakly for RANK, RANKL and TNFα. A strong statistical correlation (p<0.02) was found between the five parameters, volume of bone loss, polyethylene wear debris, RANK, RANKL and TNFα expression. Importantly, in vitro studies revealed that RANKL and TNFα synergise to increase the volume of bone resorbed, by more than seven fold, when compared to the effect of either cytokine treatment alone. This suggests that the interaction of TNFα and RANKL promotes osteoclast activity associated with polyethylene wear and therapies targeting TNF activity may be useful to treat peri-implant osteolysis.
Keywords: Osteolysis; Osteoclast; Wear debris; Polyethylene; Image analysis
Rights: © 2006 Elsevier Ltd
RMID: 0020061374
DOI: 10.1016/j.biomaterials.2006.05.054
Appears in Collections:Orthopaedics and Trauma publications

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