PURPOSE OF REVIEW: Joint replacement has revolutionized the treatment of end-stage arthritis. We highlight the key role of macrophages in the innate immune system in helping to ensure that the prosthesis-host interface remains biologically robust. RECENT FINDINGS: Osteoimmunology is of great interest to researchers investigating the fundamental biological and material aspects of joint replacement. Constant communication between cells of the monocyte/macrophage/osteoclast lineage and the mesenchymal stem cell-osteoblast lineage determines whether a durable prosthesis-implant interface is obtained, or whether implant loosening occurs. Tissue and circulating monocytes/macrophages provide local surveillance of stimuli such as the presence of byproducts of wear and can quickly polarize to pro- and anti-inflammatory phenotypes to re-establish tissue homeostasis. When these mechanisms fail, periprosthetic osteolysis results in progressive bone loss and painful failure of mechanical fixation. Immune modulation of the periprosthetic microenvironment is a potential intervention to facilitate long-term durability of prosthetic interfaces.

• Klíčová slova
• Inflammation, Innate immune system, Joint replacement, Macrophage, Osteoimmunology, Periprosthetic osteolysis, Prosthesis,
• MeSH
• artroplastiky kloubů * MeSH
• lidé MeSH
• makrofágy MeSH
• osteolýza * MeSH
• protézy kloubů * MeSH
• selhání protézy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

Clinical studies, as well as in vitro and in vivo experiments have demonstrated that byproducts from joint replacements induce an inflammatory reaction that can result in periprosthetic osteolysis (PPOL) and aseptic loosening (AL). Particle-stimulated macrophages and other cells release cytokines, chemokines, and other pro-inflammatory substances that perpetuate chronic inflammation, induce osteoclastic bone resorption and suppress bone formation. Differentiation, maturation, activation, and survival of osteoclasts at the bone-implant interface are under the control of the receptor activator of nuclear factor kappa-Β ligand (RANKL)-dependent pathways, and the transcription factors like nuclear factor κB (NF-κB) and activator protein-1 (AP-1). Mechanical factors such as prosthetic micromotion and oscillations in fluid pressures also contribute to PPOL. The treatment for progressive PPOL is only surgical. In order to mitigate ongoing loss of host bone, a number of non-operative approaches have been proposed. However, except for the use of bisphosphonates in selected cases, none are evidence based. To date, the most successful and effective approach to preventing PPOL is usage of wear-resistant bearing couples in combination with advanced implant designs, reducing the load of metallic and polymer particles. These innovations have significantly decreased the revision rate due to AL and PPOL in the last decade.

• Klíčová slova
• RANKL-RANK, Total joint replacement, aseptic loosening, bisphosphonates, debris-induced inflammation, macrophages, osteoclasts, periprosthetic osteolysis, total hip arthroplasty, total knee arthroplasty,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Extensive osteolysis adjacent to orthopedic implants is often associated with wear particles of prosthetic material. The activation of the RANKL/RANK/OPG system is considered to be a likely cause of periprosthetic osteolysis leading to implant failure. The aim of this study was to examine the possible correlation between the clinical extent of osteolysis, the number of wear particles and expression of the osteoclastic mediator RANKL (receptor activator of nuclear factor kappa B ligand) in the tissues around aseptically loosened cemented and non-cemented total hip replacements. Periprosthetic tissues were harvested from 59 patients undergoing revision of hip replacement for aseptic loosening. We observed RANKL-positive cells in 23 of our 59 patients, their presence was noted predominantly in tissues with a loosened cemented endoprosthesis. We have found that RANKL is present only in tissues with a large amount of wear debris and predominantly in cases involving loosened cemented implants.

• MeSH
• femur chemie   patologie   MeSH
• kyčelní kloub chirurgie   MeSH
• kyčelní protézy * MeSH
• lidé středního věku MeSH
• lidé MeSH
• ligand RANK analýza   MeSH
• náhrada kyčelního kloubu škodlivé účinky   přístrojové vybavení   MeSH
• osteolýza etiologie   metabolismus   patologie   chirurgie   MeSH
• reoperace MeSH
• selhání protézy * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ligand RANK MeSH
• TNFSF11 protein, human MeSH Prohlížeč

Aseptic loosening and osteolysis are considered the main long-term problems of hip arthroplasty. Pathogenesis of periprosthetic osteolysis is multifactorial, and both the biological and mechanical factors seem to play an important role. Bearing surfaces continuously generate excessive amounts of micron and submicron particles provoking an adverse inflammatory response of periprosthetic connective tissues. In general, a key role has been attributed to macrophages. Cytokines, growth factors, PGE2, and enzymes are secreted with activated periprosthetic cells resulting in formation of osteolytic granulomas. The final osteolytic step is taken predominantly by osteoclasts which are getting ready for action mainly by an osteoprotegerin ligand (RANKL) and TNFalpha. Rankl is expressed by activated macrophages, osteoblasts, and lymphocytes. In parallel, a repetitive hydraulic effect of the joint fluid is manifested on the susceptible bone.

• MeSH
• kosti a kostní tkáň patologie   MeSH
• kyčelní protézy škodlivé účinky   MeSH
• lidé MeSH
• ligand RANK MeSH
• membránové glykoproteiny fyziologie   MeSH
• náhrada kyčelního kloubu * MeSH
• osteoklasty fyziologie   MeSH
• osteolýza etiologie   patofyziologie   MeSH
• protein RANK MeSH
• reakce na cizí těleso etiologie   patologie   patofyziologie   MeSH
• reoperace MeSH
• selhání protézy * MeSH
• signální transdukce MeSH
• TNF-alfa fyziologie   MeSH
• transportní proteiny fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ligand RANK MeSH
• membránové glykoproteiny MeSH
• protein RANK MeSH
• TNF-alfa MeSH
• TNFRSF11A protein, human MeSH Prohlížeč
• TNFSF11 protein, human MeSH Prohlížeč
• transportní proteiny MeSH

Numerous studies provide detailed insight into the triggering and amplification mechanisms of the inflammatory response associated with prosthetic wear particles, promoting final dominance of bone resorption over bone formation in multiple bone multicellular units around an implant. In fact, inflammation is a highly regulated process tightly linked to simultaneous stimulation of tissue protective and regenerative mechanisms in order to prevent collateral damage of periprosthetic tissues. A variety of cytokines, chemokines, hormones and specific cell populations, including macrophages, dendritic and stem cells, attempt to balance tissue architecture and minimize inflammation. Based on this fact, we postulate that the local tissue homeostatic mechanisms more effectively regulate the pro-inflammatory/pro-osteolytic cells/pathways in patients with none/mild periprosthetic osteolysis (PPOL) than in patients with severe PPOL. In this line of thinking, 'particle disease theory' can be understood, at least partially, in terms of the failure of local tissue homeostatic mechanisms. As a result, we envision focusing current research on homeostatic mechanisms in addition to traditional efforts to elucidate details of pro-inflammatory/pro-osteolytic pathways. We believe this approach could open new avenues for research and potential therapeutic strategies.

• MeSH
• buněčné mikroprostředí imunologie   MeSH
• Hajdu-Cheney syndrom etiologie   imunologie   prevence a kontrola   MeSH
• lidé MeSH
• mediátory zánětu imunologie   MeSH
• náhrada kyčelního kloubu * MeSH
• osteogeneze MeSH
• protézy kloubů MeSH
• selhání protézy etiologie   MeSH
• zánět etiologie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mediátory zánětu MeSH

BACKGROUND: Among patients with hip joint endoprosthesis, periprosthetic osteolysis is the most common complication following primary arthroplasty, and subsequent implant loosening is the leading cause of arthroplasty revision. Causes of stability loss, though not always evident, can be mechanical, allergic, or infectious (bacterial and fungal agents) in nature. Microsporidia, widespread opportunistic fungal pathogens that infect most human tissues, are a potential infectious cause of stability loss. Infections caused by Encephalitozoon species-one of the most common microsporidial pathogens in humans-primarily localize to intestinal and respiratory tracts, but can disseminate to tissues throughout the body. METHODS: We examined 53 immunocompetent patients, 23 after revision and 30 after primary hip arthroplasty, for infection by Encephalitozoon species. Periprosthetic tissue, urine sediments, and stool samples were tested by microscopic examination and genus-specific nested polymerase chain reaction followed by genotyping. RESULTS: Ten patients had Encephalitozoon-positive periprosthetic tissues, 9 (39%) after revision and 1 (3.3%) after primary hip arthroplasty. Among the tissue-positive postrevision patients, 7 had a positive urine sample and 1 had a positive stool sample. Encephalitozoon cuniculi genotype II was identified in 88.8% (16/18) of samples. Two urine samples were positive for a novel Encephalitozoon species. CONCLUSIONS: Encephalitozoon cuniculi should be considered as a cause of osteolysis in hip periprosthetic tissue, leading to a loss of implant stability.

• MeSH
• Encephalitozoon cuniculi genetika   izolace a purifikace   MeSH
• encephalitozoonóza komplikace   MeSH
• feces mikrobiologie   MeSH
• imunokompetence MeSH
• infekce spojené s protézou mikrobiologie   moč   MeSH
• kyčelní kloub mikrobiologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada kyčelního kloubu * MeSH
• osteolýza mikrobiologie   MeSH
• polymerázová řetězová reakce MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Bone remodeling is a tightly coupled process consisting of repetitive cycles of bone resorption and formation. Both processes are governed by mechanical signals, which operate in conjunction with local and systemic factors in a discrete anatomic structure designated a basic multicellular unit (BMU). The microenvironment around total joint arthroplasty is a dynamic and complex milieu influenced by the chemical and physical stimuli associated with servicing the prosthesis. A key factor limiting the longevity of the prosthesis is polyethylene wear, which induces particle disease, and this may lead to increased and prolonged activity of BMUs resulting in periprosthetic osteolysis. Several pathways regulating BMU function have been reported in the past, including RANKL/RANK/OPG/TRAF6, TNF-alpha/TNFR/TRAF1, and IL-6/CD126/JAK/STAT. Moreover, the expression and functional activity of all these molecules can be affected by variations in their genes. These may explain the differences in severity of bone defects or prosthetic failure between patients with similar wear rates and the same prosthesis. Simultaneously, this data strongly support the theory of individual susceptibility to prosthetic failure.

• MeSH
• artroplastiky kloubů škodlivé účinky   přístrojové vybavení   MeSH
• fibroblasty metabolismus   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• lymfocyty metabolismus   MeSH
• mechanický stres MeSH
• náchylnost k nemoci MeSH
• osteoblasty metabolismus   MeSH
• osteoklasty metabolismus   MeSH
• osteolýza etiologie   metabolismus   patofyziologie   prevence a kontrola   MeSH
• protézy kloubů * MeSH
• remodelace kosti * MeSH
• rizikové faktory MeSH
• selhání protézy * MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy 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

Aseptic loosening and osteolysis are the most frequent causes of total hip or total knee arthroplasty failure. Osteolysis is induced predominantly by polyethylene particles that are produced by adhesive wear of the prosthesis. The particles trigger a complex host's reaction varying in intensity even in response to the same number of particles. These differences indicate that individual predisposition may have an important role in the pathogenesis of osteolysis. The major key mediators of wear-induced osteolysis include the cytokines RANKL, TNF-a, IL-1, IL-6 and IL-8. The inter-individual differences in the extent of bone destruction may therefore be related to variation in the amount and/or activity of these cytokines based on their gene polymorphism. Our pilot study suggests an association of some variants of the cytokine genes (e.g., IL1A-889) with a predisposition to development of severe osteolysis. If this assumption is confirmed by future investigations, this approach can facilitate the pre-operative identification of patients at risk of the development of severe periprosthetic osteolysis and premature failure of the implant.

• MeSH
• cytokiny genetika   MeSH
• genetická predispozice k nemoci * MeSH
• lidé MeSH
• ligand RANK genetika   MeSH
• osteolýza genetika   MeSH
• polymorfismus genetický * MeSH
• protézy kloubů * škodlivé účinky   MeSH
• selhání protézy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• ligand RANK MeSH

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.

• Klíčová slova
• Aseptic loosening, Immunostaining, Osteolysis, Tissue analysis, Total hip,
• MeSH
• lidé MeSH
• náhrada kyčelního kloubu * MeSH
• osteolýza * MeSH
• pojivová tkáň patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH