Inflammation time-axis in aseptic loosening of total knee arthroplasty: A preliminary study

Abstract

Objective Aseptic loosening (AL) is the most frequent long-term reason for revision of total knee arthroplasty (TKA) affecting about 15–20% patients within 20 years after the surgery. Although there is a solid body of evidence about the crucial role of inflammation in the AL pathogenesis, scared information on inflammation signature and its time-axis in tissues around TKA exists. Design The inflammation protein signatures in pseudosynovial tissues collected at revision surgery from patients with AL (AL, n = 12) and those with no clinical/radiographic signs of AL (non-AL, n = 9) were investigated by Proximity Extension Assay (PEA)-Immunoassay and immunohistochemistry. Results AL tissues had elevated levels of TNF-family members sTNFR2, TNFSF14, sFasL, sBAFF, cytokines/chemokines IL8, CCL2, IL1RA/IL36, sIL6R, and growth factors sAREG, CSF1, comparing to non-AL. High interindividual variability in protein levels was evident particularly in non-AL. Levels of sTNFR2, sBAFF, IL8, sIL6R, and MPO discriminated between AL and non-AL and were associated with the time from index surgery, suggesting the cumulative character of inflammatory osteolytic response to prosthetic byproducts. The source of elevated inflammatory molecules was macrophages and multinucleated osteoclast-like cells in AL and histiocytes and osteoclast-like cells in non-AL tissues, respectively. All proteins were present in higher levels in osteoclast-like cells than in macrophages. Conclusions Our study revealed a differential inflammation signature between AL and non-AL stages of TKA. It also highlighted the unique patient’s response to TKA in non-AL stages. Further confirmation of our preliminary results on a larger cohort is needed. Analysis of the time-axis of processes ongoing around TKA implantation may help to understand the mechanisms driving periprosthetic bone resorption needed for diagnostic/preventative strategies.

The Neuroimmune Interplay in Joint Pain: The Role of Macrophages

“…The authors found that AL tissues presented high levels of TNF-family members [sTNFR2, TNFSF14, sFasL, B cell activating factor belonging to the TNF family (sBAFF)], cytokines and chemokines (IL,8, CCL2, IL1RA/IL36, sIL6R), and growth factors [amphiregulin (sAREG), colony stimulating factor (CSF1)]. Macrophages and osteoclast-like cells are the producers of these inflammatory molecules in AL ( 101 ). The sTNFR2 in AL was already reported as having a role in the osteoclast formation, and the absence of sTNFR2 receptors impairs osteoclastogenesis ( 102 ).…”

The Mechanisms Underlying the Biological Response to Wear Debris in Periprosthetic Inflammation

“…Importantly, while extensive literature on preclinical data is already available, only moderate clinical research has been performed (Schwarz, 2014). Moreover, studies in humans have mostly focused on the AL conditions, although a different inflammatory profile was observed between AL and non-AL stages of arthroplasty (Dyskova et al, 2019). Information on the time axis of the processes occurring in the periprosthetic tissues, from arthroplasty until the implant AL, will strengthen our understanding of the mechanisms driving inflammationinduced PPOL and further support the development of effective therapeutic approaches.…”

The number of lymphocytes increases in the periprosthetic tissues with increasing time of implant service in non-metal-on-metal total joint arthroplasties: A role of metallic particles?

“…The reasons for their failure differ at least in part for both anatomical locations. However, the main long-lasting problem is aseptic loosening which means a complete loss of connection between the implant and bone bed 5 . This is a consequence of long-term maladaptation of the implant-bone interface to chronic inflammation induced by prosthetic byproducts released from THA/TKA in combination with continual mechanical load 6,7 .…”

“…This subsequently results in accumulation of stimulated osteoclasts at the border between the bone and implant. A vast body of evidence shows that polyethylene micro-and nanoparticles are the main inductors of debris-induced inflammation 5 . Recently, an attention has been drawn to metallic byproducts, particularly in relation to premature failure of metal-on-metal (MoM) prostheses 9 .…”