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

doi:10.5312/wjo.v8.i4.342

RANK-ligand and osteoprotegerin as biomarkers in the differentiation between periprosthetic joint infection and aseptic prosthesis loosening

World J Orthop. 2017 Apr 18;8(4):342-349. doi: 10.5312/wjo.v8.i4.342.

Authors

Max J Friedrich¹, Matthias D Wimmer¹, Jan Schmolders¹, Andreas C Strauss¹, Milena M Ploeger¹, Hendrik Kohlhof¹, Dieter C Wirtz¹, Sascha Gravius¹, Thomas M Randau¹

Affiliation

¹ 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.

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; Biomarker; Diagnostic; Osteoprotegerin; Periprosthetic joint infection; RANK-ligand.