RESUMEN
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).
RESUMEN
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.
RESUMEN
Current diagnostic standards for PJI rely on inflammatory markers that are typically elevated in autoimmune diseases, thus making the diagnosis of PJI in patients with rheumatoid arthritis and joint replacement particularly complicated. There is a paucity of data on differentiating PJI from rheumatoid arthritis in patients with previous arthroplasty. In this study, we retrospectively analyzed the cases of 17 patients with rheumatoid arthritis and 121 patients without rheumatoid disease who underwent surgical intervention due to microbiology-positive PJI of the hip or knee joint. We assessed clinical patient characteristics, laboratory parameters, and prosthesis survival rates in patients with and without rheumatoid arthritis and acute or chronic PJI. ROC analysis was conducted for the analyzed parameters. In patients with chronic PJI, peripheral blood CRP (p = 0.05, AUC = 0.71), synovial WBC count (p = 0.02, AUC = 0.78), synovial monocyte cell count (p = 0.04, AUC = 0.75), and synovial PMN cell count (p = 0.02, AUC = 0.80) were significantly elevated in patients with rheumatoid arthritis showing acceptable to excellent discrimination. All analyzed parameters showed no significant differences and poor discrimination for patients with acute PJI. Median prosthesis survival time was significantly shorter in patients with rheumatoid arthritis (p = 0.05). In conclusion, routinely used laboratory markers have limited utility in distinguishing acute PJI in rheumatoid patients. In cases with suspected chronic PJI but low levels of serum CRP and synovial cell markers, physicians should consider the possibility of activated autoimmune arthritis.
RESUMEN
Due to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic, a large number of elective knee replacement procedures had to be postponed in both early and late 2020 in most western countries including Germany and the UK. It is unknown how public interest and demand for total knee arthroplasties was affected. Public interest in knee pain, knee osteoarthritis and knee arthroplasty in Germany and the UK was investigated using Google Trend Analysis. In addition, we monitored for changes in patient composition in our outpatient department. As of early March in Germany and of late March in the UK, until the lockdown measures, a 50 to 60% decrease in relative search frequency was observed in all categories investigated compared to the beginning of the year. While public interest for knee pain rapidly recovered, decreased interest for knee osteoarthritis and replacement lasted until the easing of measures. Shortly prior to and during the first lockdown mean search frequency for knee replacement was significantly decreased from 39.7% and 36.6 to 26.9% in Germany and from 47.7% and 50.9 to 23.7% in the UK (Germany: p = 0.022 prior to lockdown, p < 0.001 during lockdown; UK: p < 0.0001 prior to and during lockdown). In contrast, mean search frequencies did not differ significantly from each other for any of the investigated time frames during the second half of 2020 in both countries. Similarly, during the first lockdown, the proportion of patients presenting themselves to receive primary knee arthroplasty compared to patients that had already undergone knee replacement declined markedly from 64.7% to 46.9%. In contrast, patient composition changed only marginally during the lockdown measures in late 2020 in both Germany and the UK. We observed a high level of public interest in knee arthroplasty despite the ongoing pandemic. The absence of a lasting decline in interest in primary knee arthroplasty suggests that sufficient symptom reduction cannot be achieved without surgical care for a substantial number of patients.
