gms | German Medical Science

Objectives: Prosthesis survival is significantly decreased after revision surgery due to periprosthetic joint infection (PJI). We hypothesize that despite successful treatment of infection, PJI leads to compromised bone metabolism by inflammatory cytokines and cell-cell interactions involving monocytes and monocyte-derived osteoclasts. These changes may increase the risk for unstructured bone-resorption, contributing to aseptic loosening. In this study, we investigated the presence and activity of monocytes in the peripheral blood of patients with PJI that underwent two-stage exchange surgery.

Methods: Peripheral blood specimens were collected from a total of 15 patients undergoing total knee arthroplasty (control, group A), prosthesis explantation due to PJI (group B), and reimplantation surgery (group C). Peripheral blood mononuclear cells (PMBCs) were isolated by density gradient centrifugation and stained for flow cytometry for CD33, CD11b, and CD14. Monocytes were isolated using magnetic-activated cell sorting for CD14. Osteoclastic differentiation was induced using MCSF and RANKL. After 14 days, cells were stained for actin and with Tartrate-resistant acid phosphatase (TRAP) to identify osteoclasts.

Results and conclusion: Absolute and relative monocyte numbers were found to be significantly higher in group B (0.86 cells/nL and 21.68%) compared to the control group (0.21 cells/nL and 12.40%; P=0.007 and P=0.049). In group C, absolute and relative prevalence of monocytes was 0.30 cells/nL and 13.52% (P=0.1884 and P=0.200 compared to group A). Osteoclastic differentiation potential was significantly elevated in patients with PJI (group B) compared to the control with 187.71% more osteoclasts generated after stimulation (P=0.015). Additionally, osteoclast surface area was significantly larger in group B (57.36%) than group A (15.81%; P=0.002). No significant differences for any of the analyzed parameters were found at prosthesis reimplantation in comparison to group A (+50.2% number of osteoclasts, 31.62% surface area; P=0.803 and P=0.312) or B (-46.75% number of osteoclast and 57.36% surface area; P=0.296 and P=0.198).

Elevated numbers of monocytic osteoclast-progenitor cells and osteoclastic differentiation may contribute to decreased bone volume and impact prosthesis osseointegration. While a two-stage exchange approach seems to normalize the investigated parameters, a trend towards increased osteoclastic differentiation capabilities suggest that the bone metabolism has not completely returned to physiological levels. Inhibition of monocyte-mediated osteoclastogenesis while retaining anti-microbial activity of macrophages may be an approach to reduce risk of aseptic loosening after PJI.

Figure 1. A. Absolute number of monocytes per nanoliter blood in group A, B, and C. B. Prevalence of monocytes in peripheral blood mononuclear cells (PMBCs) by flow cytometry. C. Number of osteoclasts after osteoclastic differentiation. D. Osteoclast surface area after osteoclastic differentiation.