Inflammation of Bone in Patients with Periprosthetic Joint Infections of the Knee

Overview

Journal JB JS Open Access

Date 2023 Jan 26

PMID 36698987

Authors

Lara Biedermann

Evgeniya Bandick

Yi Ren

Serafeim Tsitsilonis

Stefanie Donner

Michael Muller

Georg Duda

Carsten Perka

Arne Kienzle

Affiliations

Soon will be listed here.

Abstract

Methods: In this study, we analyzed 75 human bone and bone-marrow specimens (obtained from 65 patients undergoing revision arthroplasty with cement for the treatment of PJI) for markers of inflammation. Samples were analyzed using hematoxylin and eosin overview staining, fluorescent immunohistochemical staining, flow cytometry, and polymerase chain reaction (PCR).

Results: Leukocyte prevalence was significantly elevated at explantation (femur, +218.9%; tibia, +134.2%). While leukocyte prevalence decreased at reimplantation (femur, -49.5%; tibia, -34.2%), the number of cells remained significantly higher compared with the control group (femur, +61.2%; tibia, +54.2%). Expression of inflammatory markers interleukin (IL)-1α (femur, +2,748.7%; tibia, +1,605.9%), IL-6 (femur, +2,062.5%; tibia, +2,385.7%), IL-10 (femur, +913.7%; tibia, +897.5%), IL-12 (femur, +386.1%; tibia, +52.5%), IL-18 (femur, +805.3%; tibia, +547.7%), and tumor necrosis factor (TNF)-α (femur, +296.9%; tibia, +220.9%) was significantly elevated at prosthesis explantation in both femoral and tibial specimens. Expression remained significantly elevated at reimplantation for all inflammatory markers except IL-12 compared with the control group. Conversely, there were only limited inflammatory changes in the bone marrow environment.

Conclusions: The present study demonstrated a strong and lasting upregulation of the proinflammatory environment in the joint-surrounding osseous scaffold in patients with PJI. Our data suggest that modulating the inflammatory environment has substantial potential to improve the clinical outcome in affected patients.

Citing Articles

Immune Checkpoint Molecules as Biomarkers of Bone Infection and Clinical Outcome.

Saito M, McDonald K, Grier A, Grier A, Meghwani H, Rangel-Moreno J bioRxiv. 2025; .

PMID: 39803468 PMC: 11722373. DOI: 10.1101/2024.12.30.630837.

References

Delanois R, Mistry J, Gwam C, Mohamed N, Choksi U, Mont M . Current Epidemiology of Revision Total Knee Arthroplasty in the United States. J Arthroplasty. 2017; 32(9):2663-2668. DOI: 10.1016/j.arth.2017.03.066. View

Thomas M, Puleo D . Infection, inflammation, and bone regeneration: a paradoxical relationship. J Dent Res. 2011; 90(9):1052-61. PMC: 3169879. DOI: 10.1177/0022034510393967. View

Goldring M, Otero M . Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011; 23(5):471-8. PMC: 3937875. DOI: 10.1097/BOR.0b013e328349c2b1. View

Kienzle A, Walter S, von Roth P, Fuchs M, Winkler T, Muller M . High Rates of Aseptic Loosening After Revision Total Knee Arthroplasty for Periprosthetic Joint Infection. JB JS Open Access. 2020; 5(3). PMC: 7480970. DOI: 10.2106/JBJS.OA.20.00026. View

Karczewski D, Winkler T, Renz N, Trampuz A, Lieb E, Perka C . A standardized interdisciplinary algorithm for the treatment of prosthetic joint infections. Bone Joint J. 2019; 101-B(2):132-139. DOI: 10.1302/0301-620X.101B2.BJJ-2018-1056.R1. View

Magone K, Luckenbill D, Goswami T . Metal ions as inflammatory initiators of osteolysis. Arch Orthop Trauma Surg. 2015; 135(5):683-95. DOI: 10.1007/s00402-015-2196-8. View

Heim C, Vidlak D, Odvody J, Hartman C, Garvin K, Kielian T . Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence. J Orthop Res. 2017; 36(6):1605-1613. PMC: 5953848. DOI: 10.1002/jor.23806. View

Zhang H, Huang Y, Wang S, Fu R, Guo C, Wang H . Myeloid-derived suppressor cells contribute to bone erosion in collagen-induced arthritis by differentiating to osteoclasts. J Autoimmun. 2015; 65:82-9. PMC: 4679657. DOI: 10.1016/j.jaut.2015.08.010. View

Lehmann W, Edgar C, Wang K, Cho T, Barnes G, Kakar S . Tumor necrosis factor alpha (TNF-alpha) coordinately regulates the expression of specific matrix metalloproteinases (MMPS) and angiogenic factors during fracture healing. Bone. 2005; 36(2):300-10. DOI: 10.1016/j.bone.2004.10.010. View

10.

Janz V, Bartek B, Wassilew G, Stuhlert M, Perka C, Winkler T . Validation of Synovial Aspiration in Girdlestone Hips for Detection of Infection Persistence in Patients Undergoing 2-Stage Revision Total Hip Arthroplasty. J Arthroplasty. 2015; 31(3):684-7. DOI: 10.1016/j.arth.2015.09.053. View

11.

Korsch M, Robra B, Walther W . Cement-associated signs of inflammation: retrospective analysis of the effect of excess cement on peri-implant tissue. Int J Prosthodont. 2015; 28(1):11-8. DOI: 10.11607/ijp.4043. View

12.

Yang X, Ricciardi B, Hernandez-Soria A, Shi Y, Camacho N, Bostrom M . Callus mineralization and maturation are delayed during fracture healing in interleukin-6 knockout mice. Bone. 2007; 41(6):928-36. PMC: 2673922. DOI: 10.1016/j.bone.2007.07.022. View

13.

Mountziaris P, Spicer P, Kasper F, Mikos A . Harnessing and modulating inflammation in strategies for bone regeneration. Tissue Eng Part B Rev. 2011; 17(6):393-402. PMC: 3223017. DOI: 10.1089/ten.TEB.2011.0182. View

14.

Insall J, Thompson F, Brause B . Two-stage reimplantation for the salvage of infected total knee arthroplasty. J Bone Joint Surg Am. 1983; 65(8):1087-98. View

15.

Guo R, Yamashita M, Zhang Q, Zhou Q, Chen D, Reynolds D . Ubiquitin ligase Smurf1 mediates tumor necrosis factor-induced systemic bone loss by promoting proteasomal degradation of bone morphogenetic signaling proteins. J Biol Chem. 2008; 283(34):23084-92. PMC: 2517001. DOI: 10.1074/jbc.M709848200. View

16.

Sokhi U, Xia Y, Sosa B, Turajane K, Nishtala S, Pannellini T . Immune Response to Persistent Staphyloccocus Aureus Periprosthetic Joint Infection in a Mouse Tibial Implant Model. J Bone Miner Res. 2021; 37(3):577-594. PMC: 8940655. DOI: 10.1002/jbmr.4489. View

17.

Schmidt-Bleek K, Schell H, Schulz N, Hoff P, Perka C, Buttgereit F . Inflammatory phase of bone healing initiates the regenerative healing cascade. Cell Tissue Res. 2011; 347(3):567-73. DOI: 10.1007/s00441-011-1205-7. View

18.

Crotti T, Dharmapatni A, Alias E, Haynes D . Osteoimmunology: Major and Costimulatory Pathway Expression Associated with Chronic Inflammatory Induced Bone Loss. J Immunol Res. 2015; 2015:281287. PMC: 4433696. DOI: 10.1155/2015/281287. View

19.

Ren Y, Biedermann L, Gwinner C, Perka C, Kienzle A . Serum and Synovial Markers in Patients with Rheumatoid Arthritis and Periprosthetic Joint Infection. J Pers Med. 2022; 12(5). PMC: 9148028. DOI: 10.3390/jpm12050810. View

20.

Poss R, Thornhill T, Ewald F, Thomas W, Batte N, Sledge C . Factors influencing the incidence and outcome of infection following total joint arthroplasty. Clin Orthop Relat Res. 1984; (182):117-26. View