Lipopolysaccharide Found in Aseptic Loosening of Patients with Inflammatory Arthritis

Abstract

Aseptic loosening of orthopaedic implants occurs in the absence of clinical signs of infection. Nevertheless, bacterial endotoxins derived from subclinical infections, systemic sources, or the implant manufacturing process may contribute to aseptic loosening. Also, the rate of implant infection is greater in patients with inflammatory arthritis than in patients with osteoarthritis. We hypothesized that lipopolysaccharide, the classic endotoxin derived from gram-negative bacteria, is more prevalent in periprosthetic tissue surrounding aseptically loose implants in patients with inflammatory arthritis than in patients with osteoarthritis. To test this, we used a modified Limulus amebocyte assay not affected by beta-glucan-like molecules in mammalian tissues. Lipopolysaccharide rarely was detected in periprosthetic tissue from patients with osteoarthritis and aseptic loosening (one of six patients). In contrast, lipopolysaccharide was detected despite the absence of any clinical signs of infection in peri-prosthetic tissue from all four patients with inflammatory arthritis (rheumatoid arthritis, juvenile rheumatoid arthritis, and systemic lupus erythematosus). Lipopolysaccharide also was detected in two patients with gram-negative infections, who were included as positive control subjects. Endotoxins derived from low-grade or systemic bacteremia may be important contributors to aseptic loosening particularly in patients with autoimmune conditions such as inflammatory arthritis.

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

“…The PAMP hypothesis depends on the presence of these molecules, at least episodically, during aseptic loosening. In support of this, LPS has been detected in periprosthetic tissue from patients with inflammatory arthritis and aseptic loosening [73]. Moreover, peptidoglycan, a PAMP produced by both Gram-negative and Gram-positive bacteria, exists in synovial tissue from patients with osteoarthritis and rheumatoid arthritis [16,96] and, therefore, likely exists in periprosthetic tissue of patients with aseptic loosening.…”

Mark B. Coventry Award: Synovial C-reactive Protein: A Prospective Evaluation of a Molecular Marker for Periprosthetic Knee Joint Infection

“…The more we learn about the histopathologic characteristics of infected versus uninfected joints, the better able we will be to identify clinically relevant characteristics of infections [28,37,[39][40][41]. Drawbacks to many of these new diagnostic methods are that many of them are expensive, require specialized equipment, or are relatively time-consuming and therefore are not universally available [4,44,52].…”

Risk Factors for Aseptic Loosening Following Total Hip Arthroplasty

“…Gram-positive and gramnegative bacteria produce (as constituent components of their cell walls or as toxins) a number of molecules including endotoxins and peptidoglycans, collectively termed pathogen associated molecular patterns (PAMPs) that act as ligands for PRRs. The presence of PAMPs has been confirmed in the periprosthetic tissue of patients undergoing revision surgery for aseptic loosening 28 . Using RNA gene sequencing, the presence of bacteria in the periprosthetic biofilm surrounding loose prostheses has also now been confirmed 29 .…”