What are the local and systemic biologic reactions and mediators to wear debris, and what host factors determine or modulate the biologic response to wear particles?

Tuan, Rocky S.; Lee, Francis Young‐In; Konttinen, Yrjö T.; Wilkinson, Mark; Smith, Robert L.

doi:10.5435/00124635-200800001-00010

Cited by 126 publications

(108 citation statements)

References 56 publications

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…Those associations with aseptic loosening, in combination with those in genes that encode for proinflammatory cytokines, confirm the well-accepted concept [35,38,75,108] that aseptic loosening is primarily driven by the following stepwise process: (1) wear particles induce production of proinflammatory cytokines; (2) the proinflammatory cytokines stimulate production of RANKL; (3) RANKL increases osteoclast differentiation; and (4) the increased number of osteoclasts causes local osteolysis.…”

Section: Where Are We Now?supporting

confidence: 74%

“…Also consistent with the importance of other factors is the finding that monocyte production of proinflammatory cytokines in response to polyethylene and titanium wear particles varies greatly between individual donors [31,46]. The similar finding with different types of particles is not surprising because the different types of particles are thought to induce osteolysis through similar proinflammatory mechanisms [7,75,102,108]. This review focuses on three other factors that may modulate the effects of wear particles: (1) genetic susceptibility; (2) Toll-like receptors (TLRs); and (3) bacterial pathogenassociated molecular patterns (PAMPs).…”

Section: Introductionmentioning

confidence: 52%

“…Consistent with that possibility, antibodies that neutralize sclerostin, an inhibitor of wnt signaling, block the negative effect of polyethylene particles on implant fixation in rats by increasing bone formation and decreasing bone resorption [60]. Also consistent with that possibility, the number of osteoblasts is reduced on bone surfaces surrounding loose implants [49]; patients with high rates of bone formation have lower rates of aseptic loosening [55]; wear particles can reduce osteogenesis in vitro and in animal models [17,108]; and osteoblasts rapidly repair osteolysis induced by wear particles in young mice [48]. Another possibility is that altered wnt signaling results in skeletal anatomy that predisposes the patient to loosening.…”

Section: Where Are We Now?mentioning

confidence: 74%

See 2 more Smart Citations

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

View full text Add to dashboard Cite

Background Overwhelming evidence supports the concept that wear particles are the primary initiator of aseptic loosening of orthopaedic implants. It is likely, however, that other factors modulate the biologic response to wear particles. This review focuses on three potential other factors: genetic susceptibility, Toll-like receptors (TLRs), and bacterial pathogen-associated molecular patterns (PAMPs). Where Are We Now? Considerable evidence is emerging that both genetic susceptibility and TLR activation are important factors that modulate the biologic response to wear particles, but it remains controversial whether bacterial PAMPs also do so. Where Do We Need to Go? Detailed understanding of the roles of these other factors may lead to identification of novel therapeutic targets for patients with aseptic loosening. How Do We Get There? Highest priority should be given to polymorphism replication studies with large numbers of patients and studies to replicate the reported correlation between bacterial biofilms and the severity of aseptic loosening.

show abstract

Section: Where Are We Now?supporting

confidence: 74%

Section: Introductionmentioning

confidence: 52%

Section: Where Are We Now?mentioning

confidence: 74%

See 1 more Smart Citation

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

View full text Add to dashboard Cite

show abstract

“…Aseptic loosening has been described as a major cause for revision after THA at long-term followup [4,24] Aseptic loosening of THA includes multiple pathways, including osteolysis and mechanical failure of fixation [7]. Osteolysis is a result of macrophage-induced activation of osteoclast production and inhibition of osteoblast formation [34]. Stiffness mismatch between implant and host bone can also lead to stress shielding, which results in disuse osteopenia and can lead to fracture or implant loosening [7].…”

Section: Discussionmentioning

confidence: 99%

Association of Bisphosphonate Use and Risk of Revision After THA: Outcomes From a US Total Joint Replacement Registry

Khatod

Inacio

Dell

et al. 2015

Clinical Orthopaedics &Amp; Related Research

View full text Add to dashboard Cite

Background Total hip arthroplasty (THA) is often performed in patients who are older and may take bisphosphonates to treat a variety of conditions, most commonly osteoporosis. However, the clinical effects of bisphosphonate use on patients who have undergone THA are not well described. Questions/purposes (1) Is bisphosphonate use in patients with osteoarthritis undergoing primary THA associated with a change in the risk of all-cause revision, aseptic revision, or periprosthetic fracture compared with patients not treated with bisphosphonates? (2) Does the risk of bisphosphonate use and revision and periprosthetic fracture vary by patient bone mineral density and age? Methods A retrospective cohort study of 12,878 THA recipients for the diagnosis of osteoarthritis was conducted; 17.8% of patients were bisphosphonate users. Data sources for this study included a joint replacement registry (93% voluntary participation) and electronic health records and an osteoporosis screening database with complete capture of cases as part of the Kaiser Permanente integrated healthcare system. The endpoints for this study were revision surgery for any cause, aseptic revision, and periprosthetic fracture. The exposure of interest was bisphosphonate use; patients were considered users if prescriptions were continuously refilled for a period equal to or longer than 6 months. Bone quality (based on dual-energy x-ray absorptiometery ordered based on the National Osteoporosis Foundation's clinical guidelines taken within 5 years of the THA) and patient age (\ 65 versus C 65 years) were evaluated as effect modifiers. Patient, surgeon, and hospital factors were evaluated as confounders. Cox proportional hazards models were used. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined. Results Age-and sex-adjusted risks of all-cause (HR, 0.50; 95% CI, 0.33-0.74; p \ 0.001) and aseptic revision Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Clinical Orthopaedics and Related Research 1 neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDAapproval status, of any drug or device prior to clinical use. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research 1 editors and board members are on file with the publication and can be viewed on request. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. HR, 0.53; 95% CI,; p = 0.004) was lower in bisphosphonate users than in nonusers. The adjusted risk of periprosthetic fractures in patients o...

show abstract

“…This wear debris stimulates local macrophage and fibroblast recruitment and release of pro-inflammatory cytokines, including interleukin-1 (IL-1), IL-6, IL-18, and tumor necrosis factor (TNF), that alter the balance of osteoclast and osteoblast activity in favor of bone resorption. 1,2 Anti-inflammatory cytokines, including IL-1 receptor antagonist (IL-1Ra) and IL-10, are also produced by activated macrophages in osteolysis and act to down-regulate the production of pro-inflammatory cytokines and inhibit osteoclastogenesis. 3,4 However, the net effect of wear debris particles on the balance of pro-versus anti-inflammatory cytokines in clinical populations, and their association with susceptibility to osteolysis, are unknown.…”

mentioning

confidence: 99%

Individual susceptibility to periprosthetic osteolysis is associated with altered patterns of innate immune gene expression in response to pro‐inflammatory stimuli

Gordon

Greenfield

Eastell

et al. 2010

Journal Orthopaedic Research

View full text Add to dashboard Cite

Susceptibility to osteolysis after total hip arthroplasty (THA) varies between individuals. We examined whether patients susceptible to osteolysis (group I, n ¼ 34 subjects) after cemented Charnley THA have quantitatively different innate immune responses to pro-inflammatory stimuli versus patients without this susceptibility (group II, n ¼ 28 subjects) at a mean of 14 years after primary surgery. Extracted peripheral blood mononuclear cells were stimulated for 3 h using endotoxin (lipopolysaccharide-LPS, 100 ng/mL), endotoxinstripped titanium particles (Ti) or endotoxin-stripped particles with adherent LPS added-back (TI þ LPS). Subjects returned 1 week later and the experimental protocol was repeated. Assays for mRNA induction for interleukin (IL)-1a, IL-1b, IL-1Ra, IL-6, IL-10, IL-18, and tumor necrosis factor (TNF) were made using quantitative real-time PCR. Although baseline levels of mRNA expression were slightly lower in group I, inducibility of mRNA expression was markedly greater in group I versus group II for all cytokines in response to LPS or Ti þ LPS, and for IL-1a in response to Ti (P < 0.05). LPS or Ti þ LPS stimulation also resulted in an increase in the IL-1/IL-1Ra mRNA ratio in group I versus group II (P < 0.05). mRNA induction was highly reproducible between subject visits (r > 0.7, P < 0.001). Osteolysis-susceptible patients show repeatable, quantitatively different patterns of innate cytokine gene expression in response to pro-inflammatory stimuli versus THA patients who do not display this susceptibility. These innate immune differences may contribute to the variation in osteolysis-susceptibility observed clinically between individuals. ß

show abstract

What are the local and systemic biologic reactions and mediators to wear debris, and what host factors determine or modulate the biologic response to wear particles?

Cited by 126 publications

References 56 publications

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Association of Bisphosphonate Use and Risk of Revision After THA: Outcomes From a US Total Joint Replacement Registry

Individual susceptibility to periprosthetic osteolysis is associated with altered patterns of innate immune gene expression in response to pro‐inflammatory stimuli

Contact Info

Product

Resources

About