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The correlation of RANK, RANKL and TNFalpha expression with bone loss volume and polyethylene wear debris around hip
Christopher A Holding1, David M Findlay, Roumen Stamenkov
1Department of Pathology, The University of Adelaide, North Terrace, Adelaide, South Australia 5000, Australia.
Biomaterials
|June 30, 2006
Summary
This study found that receptor activator NF-kappaB ligand (RANKL) and tumor necrosis factor-alpha (TNFalpha) promote bone loss near artificial joints. Therapies targeting TNFalpha may help treat peri-implant osteolysis.
Area of Science:
- Orthopedics
- Immunology
- Biomaterials Science
Background:
- Peri-implant osteolysis is a significant complication of total joint replacement surgery.
- Polyethylene wear debris is implicated in the pathogenesis of osteolysis.
- Receptor activator NF-kappaB (RANK), RANK ligand (RANKL), and tumor necrosis factor-alpha (TNFalpha) are key regulators of bone turnover.
Purpose of the Study:
- To investigate the expression of RANK, RANKL, and TNFalpha in tissues affected by peri-prosthetic osteolysis.
- To determine the correlation between these factors, polyethylene wear, and bone loss.
- To assess the synergistic effect of RANKL and TNFalpha on bone resorption in vitro.
Main Methods:
- High-resolution spiral multislice CT with metal artefact suppression was used for tissue analysis.
- Immunohistochemical analysis was performed on synovial tissue from revision and control hip replacement surgeries.
- In vitro studies were conducted to evaluate the combined effect of RANKL and TNFalpha on bone resorption.
Main Results:
- RANK, RANKL, and TNFalpha were highly expressed in multinucleated cells containing polyethylene debris in revision tissues.
- Control tissues showed weak expression of these factors.
- A significant correlation was observed between bone loss volume, polyethylene wear, and the expression of RANK, RANKL, and TNFalpha (p<0.02).
- In vitro, RANKL and TNFalpha synergistically increased bone resorption by over sevenfold compared to individual treatments.
Conclusions:
- The interaction between TNFalpha and RANKL promotes osteoclast activity associated with polyethylene wear.
- Targeting TNFalpha may be a potential therapeutic strategy for peri-implant osteolysis.
