Periprosthetic Joint Infection Caused by Gram-Positive Versus Gram-Negative Bacteria: Lipopolysaccharide, but not Lipoteichoic Acid, Exerts Adverse Osteoclast-Mediated Effects on the Bone

Abstract

Periprosthetic joint infection (PJI)—the most common cause of knee arthroplasty failure—may result from Gram-positive (GP) or Gram-negative (GN) bacterial infections. The question as to whether PJI due to GP or GN bacteria can lead to different rates of aseptic loosening after reimplantation remains open. We have investigated this issue through a retrospective review of clinical records obtained from 320 patients with bacterial PJI. The results revealed that, compared with GP infections, GN infections were associated with an increased risk of aseptic loosening. In animal studies, mice underwent intrafemoral injection of lipopolysaccharide (LPS) from GN bacteria or lipoteichoic acid (LTA) from GP bacteria. We demonstrate that LPS—but not LTA—reduced both the number of trabeculae and the bone mineral density in mice. In addition, LPS-treated mice exhibited a reduced body weight, higher serum osteocalcin levels, and an increased number of osteoclasts. LPS accelerated monocyte differentiation into osteoclast-like cells, whereas LTA did not. Finally, ibudilast—a toll-like receptor (TLR)-4 antagonist—was found to inhibit LPS-induced bone loss and osteoclast activation in mice. Taken together, our data indicate that PJI caused by GN bacteria portends a higher risk of aseptic loosening after reimplantation, mainly because of LPS-mediated effects on osteoclast differentiation.

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection

“…In addition, the current two-stage revision for PJI that involves debridement and an antibiotic-impregnated polymethylmethacrylate spacer has exhibited outcome failure [34,35]. We previously published a retrospective review of clinical records obtained from 320 patients with bacterial PJI [20]. The study demonstrated that GN bacterial infections were associated with an increased risk of aseptic loosening as compared with GP bacterial infections [20].…”

“…We previously published a retrospective review of clinical records obtained from 320 patients with bacterial PJI [20]. The study demonstrated that GN bacterial infections were associated with an increased risk of aseptic loosening as compared with GP bacterial infections [20]. Moreover, LPS-treated mice had reduced body weight, higher serum osteocalcin levels, and more osteoclasts [20].…”

“…We previously demonstrated that LPSs have adverse osteoclast-mediated effects on the bone in vivo [20]. Thus, we evaluated whether anti-IL-16 antibody treatment prevents LPS-mediated cathepsin K activation and bone loss.…”

“…Currently, these cytokines are believed to promote the development of septic arthritis [17][18][19].PJI can result from Gram-positive (GP) or Gram-negative (GN) bacterial infections. Our previous retrospective study revealed that GN infections were associated with an increased risk of aseptic loosening as compared with GP infections [20]. The cell walls of GP bacteria contain lipoteichoic acid (LTA) components, whereas those of GN bacteria contain components of lipopolysaccharide (LPS).…”

“…The cell walls of GP bacteria contain lipoteichoic acid (LTA) components, whereas those of GN bacteria contain components of lipopolysaccharide (LPS). In studies of mice receiving intrafemoral injections of LPS or LTA, LPS reduced both the number of trabeculae and bone mineral density, whereas LTA did not have this effect [20]. In addition, disruption of the balance between bone resorption and formation has been observed in bone infections [21].…”