Introduction: Total joint replacement is one of the most common, safe, and efficacious operations in all of surgery. However, one major long-standing and unresolved issue is the adverse biological reaction to byproducts of wear from the bearing surfaces and modular articulations. These inflammatory reactions are mediated by the innate and adaptive immune systems.Areas covered: We review the etiology and pathophysiology of implant debris-associated inflammation, the clinical presentation and detailed work-up of these cases, and the principles and outcomes of non-operative and operative management. Furthermore, we suggest future strategies for prevention and novel treatments of implant-related adverse biological reactions.Expert opinion: The generation of byproducts from joint replacements is inevitable, due to repetitive loading of the implants. A clear understanding of the relevant biological principles, clinical presentations, investigative measures and treatments for implant-associated inflammatory reactions and periprosthetic osteolysis will help identify and treat patients with this issue earlier and more effectively. Although progressive implant-associated osteolysis is currently a condition that is treated surgically, with further research, it is hoped that non-operative biological interventions could prolong the lifetime of joint replacements that are otherwise functional and still salvageable.

• Klíčová slova
• Joint replacement, hip, joint arthroplasty, knee, osteolysis, particles, wear,
• MeSH
• chemokiny metabolismus   MeSH
• diferenciální diagnóza MeSH
• lidé MeSH
• protézy kloubů škodlivé účinky   MeSH
• selhání protézy * MeSH
• výsledek terapie MeSH
• zánět diagnóza   diagnostické zobrazování   etiologie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• chemokiny MeSH

Millions of total joint replacements are performed annually worldwide, and the number is increasing every year. The overall proportion of patients achieving a successful outcome is about 80-90% in a 10-20-years time horizon postoperatively, periprosthetic osteolysis (PPOL) and aseptic loosening (AL) being the most frequent reasons for knee and hip implant failure and reoperations. The chemokine system (chemokine receptors and chemokines) is crucially involved in the inflammatory and osteolytic processes leading to PPOL/AL. Thus, the modulation of the interactions within the chemokine system may influence the extent of PPOL. Indeed, recent studies in murine models reported that (i) blocking the CCR2-CCL2 or CXCR2-CXCL2 axis or (ii) activation of the CXCR4-CXCL12 axis attenuate the osteolysis of artificial joints. Importantly, chemokines, inhibitory mutant chemokines, antagonists of chemokine receptors, or neutralizing antibodies to the chemokine system attached to or incorporated into the implant surface may influence the tissue responses and mitigate PPOL, thus increasing prosthesis longevity. This review summarizes the current state of the art of the knowledge of the chemokine system in human PPOL/AL. Furthermore, the potential for attenuating cell trafficking to the bone-implant interface and influencing tissue responses through modulation of the chemokine system is delineated. Additionally, the prospects of using immunoregenerative biomaterials (including chemokines) for the prevention of failed implants are discussed. Finally, this review highlights the need for a more sophisticated understanding of implant debris-induced changes in the chemokine system to mitigate this response effectively.

• Klíčová slova
• aseptic loosening, chemokine receptors, immunoregenerative implant, osteolysis, therapeutics, tissue homeostasis, wear particles,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. This may be driven by functional polymorphisms in the genes for cytokines and cytokine receptors involved in the development of osteolysis in THA, thereby having an effect on the individual's phenotype. METHODS: We performed a study on 22 single-nucleotide polymorphisms (SNPs) for 11 cytokines and two cytokine receptor candidate genes for association with severity of acetabular osteolysis and risk to failure in THA. Samples from 205 unrelated Caucasian patients with cementless type THA (ABG 1) were investigated. Distribution of investigated SNP variants between the groups of mild and severe acetabular osteolysis was determined by univariate and multivariate analysis. Time-dependent output variables were analyzed by the Cox hazards model. RESULTS: Univariate analysis showed: 1) TNF-238*A allele was associated with severe osteolysis (odds ratio, OR = 6.59, p = 0.005, population attributable risk, PAR 5.2%); 2) carriers of the IL6-174*G allele were 2.5 times more prone to develop severe osteolysis than non-carriers (OR = 2.51, p = 0.007, PAR = 31.5%); 3) the carriage of IL2-330*G allele was associated with protection from severe osteolysis (OR = 0.55, p = 0.043). Based on logistic regression, the alleles TNF-238*A and IL6-174*G were independent predictors for the development of severe acetabular osteolysis. Carriers of TNF-238*A had increased cumulative hazard of THA failure according to Cox model (p = 0.024). In contrast, IL2-330*G allele predicted lower cumulative hazard of THA failure (p = 0.019). CONCLUSION: Genetic variants of proinflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL. In this way, presence of the minor TNF allele could increase the cumulative risk of THA failure. Conversely, SNP in the IL2 gene may protect carriers from the above THA complications.

• MeSH
• alely MeSH
• cytokiny genetika   MeSH
• dospělí MeSH
• genetické asociační studie * MeSH
• interleukin-2 genetika   MeSH
• interleukin-6 genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada kyčelního kloubu škodlivé účinky   MeSH
• odds ratio MeSH
• osteolýza etiologie   genetika   MeSH
• proporcionální rizikové modely MeSH
• receptory cytokinové genetika   MeSH
• rizikové faktory MeSH
• selhání protézy * MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cytokiny MeSH
• interleukin-2 MeSH
• interleukin-6 MeSH
• receptory cytokinové MeSH
• TNF-alfa MeSH