Osteoclastogenesis-related cytokines and peri-prosthetic osteolysis in revision metal-on-metal total hip replacements



Peri-prosthetic osteolysis is a major cause for revision hip arthroplasty; various cytokines including those in the osteoclastogenesis pathway have been identified as potentially key in the osteolysis process. Adverse reactions to metal debris in metal-on-metal total hip replacements have led to an increase in revision procedures. This study examines the levels of osteoclastogenesis-related cytokines in serum and synovial fluid samples obtained from patients at the time of revision metal-on-metal total hip replacement and compares between patients with and without radiographic evidence of peri-prosthetic osteolysis.


Sandwich ELISA techniques were used to detect IL-6, IL-18, M-CSF, sRANKL and OPG in the samples. Results were analysed with linear regression, Fisher’s tests and t-tests; p<0.05 considered significant. Samples from 36 patients (18 with osteolysis, 18 without osteolysis) were analysed.


There was wide variation in the detectable levels of cytokines. No significant differences were found between patients with and without osteolysis in mean synovial fluid levels of IL-6 (p = 0.863), IL-18 (p = 0.324), M-CSF (p = 0.508), sRANKL (p = 0.884), OPG (p = 0.776) or mean serum levels of OPG (p = 0.993) or sRANKL (p = 0.565) (insufficient detection of IL-6, IL-18 or M-CSF in serum samples). A correlation was found between synovial fluid levels of IL-6 and OPG in patients without osteolysis (r2 = 0.618, p<0.001) but not with osteolysis (r2 = 0.0004).


These results indicate that the process of peri-prosthetic osteolysis is complex and multifactorial; there may also be an influence of metallosis. Further research is needed to increase understanding of peri-prosthetic osteolysis and influence clinical practice.

Hip Int 2015; 25(4): 355 - 360




Sarah E. Eastwood, Alun John, Stephen A. Jones, Helen Hodgson, Deborah Mason, Rachel Waddington, Xiaoqing Wei

Article History


Financial support: The study was funded via the Department of Trauma and Orthopaedics, University Hospital Wales and the Arthritis Research UK Biomechanics and Bioengineering Centre, Cardiff University.
Conflict of interest: None.

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  • Department of Trauma and Orthopaedics, University Hospital Wales, Cardiff - UK
  • Arthritis Research UK Biomechanics and Bioengineering Centre, Cardiff University, Cardiff - UK
  • School of Biosciences, Cardiff University, Cardiff - UK
  • Tissue Engineering and Reparative Dentistry, School of Dentistry, Cardiff University, Cardiff - UK

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