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

Abstract

AIMTo assess serum levels of RANK-ligand (RANKL) and osteoprotegerin (OPG) as biomarkers for periprosthetic joint infection (PJI) and compare their accuracy with standard tests.METHODSOne 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.RESULTSAll 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).CONCLUSIONLower RANKL and higher OPG concentrations could be detected in PJI, without statistical significance.

The inflammatory response to bone infection – a review based on animal models and human patients

“…A moderate upregulation of RANKL at the osteolytic cite compared to a distant site was also reported (31). In addition, there was no deference in the serum level of RANKL in patients with PJI and aseptic loosening (32).…”

Fabrication and in vitro biological activity of functional pH-sensitive double-layered nanoparticles for dental implant application

“…Studies have revealed that OPG plays an important role in inhibiting osteoclastogenesis as a final effector of bone formation. 31 In this study, OPG was released from the double-layered nanoparticles in group A, which inhibited the differentiation and maturation of osteoclasts. Compared with group B, only a small amount of OPG was released from the nanoparticles, so the inhibitory effect on the generation of osteoclasts was not as strong as that in group B.…”

A Prospective Assessment of Periprosthetic Bone Mineral Density and Osteoimmunological Biomarkers Variations After Total Knee Replacement Surgery

“…Despite improvements in prosthetic design and surgical techniques, aseptic loosening resulting from osteolysis or peri-prosthetic bone loss is a major cause of premature failure of prosthetic knee surgery. The diagnosis of early aseptic loosening is based on clinical and radiographic evaluation, but biomarkers are currently gaining interest for the preoperative differentiation between septic and aseptic loosening (1).…”

“…Collecting these data could help to estimate the risk of aseptic loosening even before implantation of the first prosthesis (1)(2)(3).…”