Increased local bone turnover in patients with chronic periprosthetic joint infection

Abstract

Aims: The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI.

Methods: Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20).

Results: PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp.

Conclusion: This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations.

Fig. 1

Periprosthetic bone microstructure in periprosthetic joint infection (PJI) compared to controls and aseptic revisions. a) Representative histological images (von Kossa staining) from the control, aseptic, and PJI groups. b) Quantification of bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). c) Quantification of osteoid volume per bone volume (OV/BV), osteoid surface per bone surface (OS/BS), and osteoid thickness (O.Th). Microstructural bone parameters and osteoid parameters were compared between the control, aseptic, and PJI groups. Boxes represent 25% and 75% percentiles, lines represent median, whiskers represent range, and coloured symbols represent individual values. One-way analysis of variance with Tukey's multiple comparison test was used for normal distributed data and Kruskal–Wallis test with Dunn’s multiple comparison test was used for non-parametric data. Exact p-values are reported unless p < 0.001.

Fig. 2

Cellular bone turnover parameters of periprosthetic joint infection (PJI) compared to controls and aseptic revisions. a) Representative histological images (toluidine blue staining) from the control, aseptic, and PJI groups. b) Quantification and comparison of cellular bone turnover parameters (number of osteoblasts per bone perimeter (N.Ob/B.Pm), osteoblast surface per bone surface (Ob.S/BS), number of osteoclasts per bone perimeter (N.Oc/B.Pm), osteoclast surface per bone surface (Oc.S/BS)) between the control, aseptic, and PJI groups. Boxes represent 25% and 75% percentiles, lines represent median, whiskers represent range, and coloured symbols represent individual values. c) Detailed histological images of toluidine blue staining and tartrate-resistant acid phosphatase (TRAP) staining from PJI patients. Red arrows indicate osteoclasts. One-way analysis of variance with Tukey’s multiple comparison test was used for normal distributed data and Kruskal–Wallis test with Dunn’s multiple comparison test was used for non-parametric data. Exact p-values are reported unless p < 0.001.

Fig. 3

Associations between prosthesis survival and histological, periprosthetic bone tissue parameters in the periprosthetic joint infection group. Linear regression analysis between prosthesis survival in months and skeletal parameters (bone volume per tissue volume (BV/TV), osteoid volume per bone volume (OV/BV), number of osteoblasts per bone perimeter (N.Ob/B.Pm), number of osteoclasts per bone perimeter (N.Oc/B.Pm)) (n = 20). Exact p-values and R² values are displayed.

Fig. 4

Associations between laboratory inflammation markers and histological bone parameters in the periprosthetic joint infection group. a) Linear regression analysis between serum CRP and bone parameters (bone volume per tissue volume (BV/TV), osteoid volume per bone volume (OV/BV), number of osteoblasts per bone perimeter (N.Ob/B.Pm), number of osteoclasts per bone perimeter (N.Oc/B.Pm)) (n = 20). b) Linear regression analysis between synovial white blood cell (WBC) count and the same bone parameters (n = 15). Exact p-values (unless < 0.001) and R² values are depicted. **p < 0.05.

Fig. 5

Comparison of bone metabolism parameters between patients with different periprosthetic joint infection (PJI) pathogens. Quantification and comparison of a) microstructural, b) osteoid, and c) cellular bone parameters between PJI specimens obtained from patients with Staphylococcus aureus, Staphylococcus epidermidis, and Cutibacterium spp. infections. Boxes represent 25% and 75% percentiles, lines represent median, whiskers represent range, and coloured symbols represent individual values. One-way analysis of variance with Tukey’s multiple comparison test was used for normal distributed data and Kruskal–Wallis test with Dunn’s multiple comparison test was used for non-parametric data. Exact p-values are reported unless p < 0.001. BV/TV, bone volume per tissue volume; N.Ob/B.Pm, number of osteoblasts per bone perimeter; N.Oc/B.Pm, number of osteoclasts per bone perimeter; Ob.S/BS, osteoblast surface per bone surface; Oc.S/BS, osteoclast surface per bone surface; OS/BS, osteoid surface per bone surface; O.Th, osteoid thickness; OV/BV, osteoid volume per bone volume; Tb.N, trabecular number; Tb.Sp, trabecular separation; Tb.Th, trabecular thickness.