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.
Highlights
Periprosthetic joint infection (PJI)—the most common cause of knee arthroplasty failure—accounts for 16–25% of failed total knee replacements [1,2,3] and is the third most common indication for revision hip arthroplasty [4,5,6,7,8]
Accumulating evidence supports the detrimental effects of bacteria on bone formation [16], the question as to whether PJI caused by Gram-positive (GP) or Gram-negative (GN) bacteria can lead to different rates of aseptic loosening after reimplantation remains open
We performed a clinical study to examine whether PJI caused by GP or GN bacteria can lead to different rates of aseptic loosening after reimplantation
Summary
Periprosthetic joint infection (PJI)—the most common cause of knee arthroplasty failure—accounts for 16–25% of failed total knee replacements [1,2,3] and is the third most common indication for revision hip arthroplasty [4,5,6,7,8]. Accumulating evidence supports the detrimental effects of bacteria on bone formation [16], the question as to whether PJI caused by Gram-positive (GP) or Gram-negative (GN) bacteria can lead to different rates of aseptic loosening after reimplantation remains open. LPS has inhibitory effects on osteoblasts by inhibiting their differentiation [18] and promoting apoptosis [19]. It can decrease alkaline phosphatase activity and downregulate osteogenic genes [20], inducing inflammatory bone loss [21]. We performed a clinical study to examine whether PJI caused by GP or GN bacteria can lead to different rates of aseptic loosening after reimplantation. We used a preclinical model to test whether ibudilast—a toll-like receptor (TLR)-4 antagonist—may prevent bacterial-induced bone resorption
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