Contributions of human tissue analysis to understanding the mechanisms of loosening and osteolysis in total hip replacement

Abstract

Aseptic loosening and osteolysis are the most frequent late complications of total hip arthroplasty (THA) leading to revision of the prosthesis. This review aims to demonstrate how histopathological studies contribute to our understanding of the mechanisms of aseptic loosening/osteolysis development. Only studies analysing periprosthetic tissues retrieved from failed implants in humans were included. Data from 101 studies (5532 patients with failure of THA implants) published in English or German between 1974 and 2013 were included. “Control” samples were reported in 45 of the 101 studies. The most frequently examined tissues were the bone-implant interface membrane and pseudosynovial tissues. Histopathological studies contribute importantly to determination of key cell populations underlying the biological mechanisms of aseptic loosening and osteolysis. The studies demonstrated the key molecules of the host response at the protein level (chemokines, cytokines, nitric oxide metabolites, metalloproteinases). However, these studies also have important limitations. Tissues harvested at revision surgery reflect specifically end-stage failure and may not adequately reveal the evolution of pathophysiological events that lead to prosthetic loosening and osteolysis. One possible solution is to examine tissues harvested from stable total hip arthroplasties that have been revised at various time periods due to dislocation or periprosthetic fracture in multicenter studies.

Peri-prosthetic tissue cells show osteogenic capacity to differentiate into the osteoblastic lineage

“…Since there is no suitable tissue to serve as a control for peri‐prosthetic tissue, we used different control cell lines to determine the relative expression. A high‐variation in the gene expression levels between donors was observed, indicating heterogeneous populations of cells, which is in line with several studies evaluating the cellular content of peri‐prosthetic tissue 43, 44, 45. Although we did not find an association between the responsiveness to osteogenic stimuli and the cell content, it is not excluded that the high‐inter‐donor variability in gene expression levels might account for the high‐inter‐donor variability in response to osteogenic stimuli.…”

Hypersensitivity reactions to metal implants: laboratory options

“…Regarding histological analysis of periprosthetic tissues, past investigations evidenced the presence of metallic aggregates in the perilesional area, as well as perivascular infiltrations of T-cells and macrophages in the tissue sections [46, 47]. …”

Blockade of NF-κB and MAPK pathways by ulinastatin attenuates wear particle-stimulated osteoclast differentiation in vitro and in vivo

“…Although clinical success and increasing popularity in the surgical population have driven its indications to more and more young and physically demanding patients, wear particle-induced PPO and consequent AL, so-called ‘particle disease’, has been the most common cause of revision of major arthroplasties, which remains a major problem for these patients. The term ‘particle disease’ was coined by Dr William Harris to stress the importance of wear particles generated by a prosthesis for induction of host response [14,21]. The process of AL is believed to begin with the generation of wear particles from implant surfaces which are phagocytosed by immune cells leading to inflammatory cytokine release (such as IL-6, TNF-α, IL-1β and MMPs) and subsequent osteolysis [2,5,22–28].…”

“…However, wear particles, originating from the implant component, stimulate the release and phagocytic activity of monocytes and macrophages around periprosthetic tissue, and generate a host of proinflammatory cytokines, including tumour necrosis factor-α (TNF-α), MMPs, interleukin-1α (IL-1α) and IL-6 [3,4]. The resulting inflammatory reaction is widely considered to be the main triggering cause of periprosthetic osteolysis (PPO) and consequent aseptic loosening (AL), so-called ‘particle disease’, which may result in failure of the implant necessitating the revision of arthroplasty [5–8].…”