Physiopathology of Prosthetic Joint Infections

Study Overview
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Brief Summary
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This study aim to explore cellular responses of bone and immune cells to bacterial infections observed in patients with prosthetic joint infections. The investigators will analyze clinical data and tissue samples collected from patients undergoing surgery as part of their usual care for prosthetic joint infections. These research will be conducted on three different hospitals in Paris: Lariboisière (AP-HP), Cochin (AP-HP) and Croix Saint-Simon.

Detailed Description
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The number of prosthetic joint infections (PJI) new cases in France is estimated at 2000/2500 cases per year. PJI, mainly caused by staphylococci, are serious infections responsible for significant morbidity result of inflammation and bone destruction (osteomyelitis). Despite optimal medical and surgical management, a risk of failure and recurrence exists, which varies depending on the situation. In addition to the deterioration in patients' quality of life, the economic cost for the health care system is very high, in particular because of prolonged hospitalizations, complex treatments, and frequent readmissions. Thus, the adequate management of PJI is a major public health issue. In this context, new therapeutic approaches are urgent medical needs for the management of patients with PJI. Thus, the identification of the biological mechanisms (immunology, microbiology, bone physiology) underlying these infections is essential. Indeed, the impact of bacterial infections on bone homeostasis is poorly documented. Although several biological mechanisms have been suggested the host-pathogen interaction and the close links between bacterial infection and biological response of bone cells to microorganisms and their environment warrant to be explored.

Official Title
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Physiopathology of Prosthetic Joint Infections : a Pilot Study

Conditions
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Prosthetic-joint Infection

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years-old and older Patient eligible for lower limb revision surgery (revision surgery for infected or non-infected prosthesis) Patient affiliated to a social security system Oral consent to the research Exclusion Criteria: NA

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| septic samples<br>patients undergoing revision surgery for prosthetic joint infection | |
| aseptic samples<br>patients undergoing revision surgery for prosthetic replacement without infection | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| markers of bone loss | Immunohistochemistry detection of Tartrate-resistant acid phosphatase cells (TRAP); cathepsin K; Matrix Metalloproteinase 9 (MMP9); sclerostin | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| markers of cellular activity in the bone microenvironment | immunohistochemistry detection of nuclear factor-activated T cells c1 (NFATc1); Matrix Metalloproteinase 9 (MMP9); Fibroblast growth factor 23 (FGF23) | 12 months | 
| immune-profiling of bone microenvironment | mapping lymphoid and myeloid cells by spectral flow cytometry assay | 12 months | 
| inflammatory mediators in the bone microenvironment | flow cytometry quantification of cytokine producing cells | 12 months | 
| differentiation between osteoclasts from mononuclear phagocytes | enzyme-linked immunosorbent (ELISA) and/or flow cytometry assays using specific antibodies | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prosthetic joint infection, prosthesis loosening, Staphylococcus, osteoblast, immune system, microenvironment