RESUMO
After periprosthetic joint infection (PJI)-dependent revision surgery, a significantly elevated number of patients suffer from prosthesis failure due to aseptic loosening and require additional revision surgery despite clearance of the initial infection. The mechanisms underlying this pathology are not well understood, as it has been assumed that the bone stock recovers after revision surgery. Despite clinical evidence suggesting decreased osteogenic potential in PJI, understanding of the underlying biology remains limited. In this study, we investigated the impact of PJI on bone homeostasis in a two-stage exchange approach at explantation and reimplantation. Sixty-four human tibial and femoral specimens (20 control, 20 PJI septic explantation, and 24 PJI prosthesis reimplantation samples) were analyzed for their bone microstructure, cellular composition, and expression of relevant genetic markers. Samples were analyzed using X-ray microtomography, Alcian blue and tartrate-resistant acid phosphatase staining, and RT-qPCR. In patients with PJI, bone volume (BV/TV; 0.173 ± 0.026; p < 0.001), trabecular thickness (164.262 ± 18.841 µm; p < 0.001), and bone mineral density (0.824 ± 0.017 g/cm2 ; p = 0.049) were reduced; trabecular separation (1833.939 ± 178.501 µm; p = 0.005) was increased. While prevalence of osteoclasts was elevated (N.Oc/BS: 0.663 ± 0.102, p < 0.001), osteoblast cell numbers were lower at explantation (N.Ob/BS: 0.149 ± 0.021; p = 0.047). Mean expression of bone homeostasis markers osteocalcin, osteopontin, Runx2, TSG-6, and FGF-2 was significantly reduced at prosthesis explantation. Despite partial recovery, all analyzed parameters were still significantly impacted at reimplantation. In contrast, mean expression of osteoclastogenesis-stimulating cytokine IL-17a was significantly increased at both explantation and reimplantation. In this study, we found a strong and lasting impact of PJI on the bone homeostasis on a molecular, cellular, and microstructural level. These changes may be responsible for the increased risk of prosthesis failure due to aseptic loosening. Our data suggest there is significant potential in modulating bone homeostasis to improve prosthesis fixation and long-term clinical outcome in affected patients. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
RESUMO
Despite the general success of total knee arthroplasty (TKA), addressing periprosthetic joint infection (PJI) and the resulting long-term complications is a growing medical need given the aging population and the increasing demand for arthroplasty. A larger proportion of patients face revision surgery because of the long-term complication of aseptic loosening despite clearance of the infection. The pathomechanisms leading to prosthetic loosening are not understood as it has been widely assumed that the bone stock recovers after explantation revision surgery. While clinical observations suggest a reduced osteogenic potential in patients with PJI, knowledge regarding the relevant biology is sparse. In the present study, we investigated the inflammatory impact of PJI on the bone and bone marrow in the vicinity of the joint. Additionally, we evaluated changes in the local inflammatory environment in a 2-stage exchange at both explantation and reimplantation. 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.