Clinical Trials Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Apr 18, 2017; 8(4): 342-349
Published online Apr 18, 2017. doi: 10.5312/wjo.v8.i4.342
RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic prosthesis loosening
Max J Friedrich, Matthias D Wimmer, Jan Schmolders, Andreas C Strauss, Milena M Ploeger, Hendrik Kohlhof, Dieter C Wirtz, Sascha Gravius, Thomas M Randau
Max J Friedrich, Matthias D Wimmer, Jan Schmolders, Andreas C Strauss, Milena M Ploeger, Hendrik Kohlhof, Dieter C Wirtz, Sascha Gravius, Thomas M Randau, Department of Orthopedics and Trauma Surgery, University Clinic of Bonn, 53125 Bonn, Germany
Author contributions: Friedrich MJ, Gravius S and Randau TM conceived and designed the research; Friedrich MJ, Wimmer MD, Ploeger MM, Kohlhof H, Strauss AC, Gravius S and Randau TM performed the experiments; Friedrich MJ, Randau TM, Schmolders J, Kohlhof H and Gravius S contributed to patient recruitment and data collection; Randau TM, Friedrich MJ, Wimmer MD, Strauss AC, Kohlhof H, Schmolders J, Ploeger MM and Gravius S analyzed the data; Randau TM, Friedrich MJ, Wimmer MD, Strauss AC, Schmolders J, Ploeger MM, Kohlhof H, Wirtz DC and Gravius S wrote the paper.
Supported by The “Deutsche Arthrose-Hilfe e.V.”, No. P192-A362-2009-12.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the University of Bonn (No. 046/09).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Not declared.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Thomas M Randau, MD, Department of Orthopedics and Trauma Surgery, University Clinic of Bonn, Sigmund Freud Str. 25, 53125 Bonn, Germany. thomas.randau@ukbonn.de
Telephone: +49-228-28714460 Fax: +49-228-28715130
Received: October 12, 2016
Peer-review started: October 17, 2016
First decision: December 15, 2016
Revised: January 10, 2017
Accepted: February 8, 2017
Article in press: February 13, 2017
Published online: April 18, 2017
Processing time: 186 Days and 21.2 Hours
Abstract
AIM

To assess serum levels of RANK-ligand (RANKL) and osteoprotegerin (OPG) as biomarkers for periprosthetic joint infection (PJI) and compare their accuracy with standard tests.

METHODS

One hundred and twenty patients presenting with a painful total knee or hip arthroplasty with indication for surgical revision were included in this prospective clinical trial. Based on standard diagnostics (joint aspirate, microbiological, and histological samples) and Musculoskeletal Infection Society consensus classification, patients were categorized into PJI, aseptic loosening, and control groups. Implant loosening was assessed radiographically and intraoperatively. Preoperative serum samples were collected and analyzed for RANKL, OPG, calcium, phosphate, alkaline phosphatase (AP), and the bone-specific subform of AP (bAP). Statistical analysis was carried out, testing for significant differences between the three groups and between stable and loose implants.

RESULTS

All three groups were identical in regards to age, gender, and joint distribution. No statistically significant differences in the serum concentration of RANKL (P = 0.16) and OPG (P = 0.45) were found between aseptic loosening and PJI, with a trend towards lower RANKL concentrations and higher OPG concentrations in the PJI group. The RANKL/OPG ratio was significant for the comparison between PJI and non-PJI (P = 0.005). A ratio > 60 ruled out PJI in all cases (specificity: 100%, 95%CI: 89, 11% to 100.0%) but only 30% of non-PJI patients crossed this threshold. The positive predictive value remained poor at any cut-off. In the differentiation between stable and loose implants, none of the parameters measured (calcium, phosphate, AP, and bAP) showed a significant difference, and only AP and bAP measurements showed a tendency towards higher values in the loosened group (with P = 0.09 for AP and P = 0.19 for bAP).

CONCLUSION

Lower RANKL and higher OPG concentrations could be detected in PJI, without statistical significance.

Keywords: Aseptic loosening; Diagnostic; RANK-ligand; Periprosthetic joint infection; Biomarker; Osteoprotegerin

Core tip: No statistically significant differences in the serum concentration of RANK-ligand (RANKL) and osteoprotegerin (OPG) were found between aseptic loosening and periprosthetic joint infection (PJI) with a certain trend of lower concentrations in the PJI group. Nevertheless, a RANKL/OPG ratio > 60 ruled out PJI in all cases. In the differentiation between a stable and loose implant the parameters measured showed no significant difference, which let to the conclusion that the sole use of these parameters for differentiating PJI and aseptic loosening cannot be recommended. RANK and OPG may have utility as a conformation test but are not an effective screening parameter for the discrimination of PJI and AL.