Metal-on-metal hips: cobalt can induce an endotoxin-like response

Tyson-Capper, Alison; Lawrence, Helen; Holland, J; Deehan, David J.; Kirby, John A.

doi:10.1136/annrheumdis-2012-202468

Cited by 37 publications

(29 citation statements)

References 8 publications

(8 reference statements)

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“…It is intriguing that oxidized alkane polymers derived from UHMWPE particles can accumulate in periprosthetic tissue and can activate TLR1/TLR2 heterodimers but cannot activate TLR3 or TLR4 [64,65]. Moreover, it has recently been reported that human TLR4 can be activated by cobalt or nickel ions [88,110], both of which can be released by corrosion of cobaltchromium implants [39]. Functional studies have shown that deletion of TLR2 and/or TLR4 in murine systems substantially reduces the in vitro and in vivo responses to titanium [8,37], UHMWPE [40], cobalt-chromium [85], and hydroxyapatite [34] particles.…”

Section: Toll-like Receptorsmentioning

confidence: 99%

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

Greenfield

2014

Clin Orthop Relat Res

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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.

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Section: Toll-like Receptorsmentioning

confidence: 99%

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

Greenfield

2014

Clin Orthop Relat Res

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“…Recent studies have shown that cobalt ions released from MOM arthroplasties have the potential to activate human toll-like receptor 4 (TLR4) of the innate immune system, and activate a proinflammatory response—which can vary between patients due to genetic factors (Corr and O’Neill 2009, Konttinen and Pajarinen 2013, Potnis et al 2013, Tyson-Capper et al 2013). Thus, we cannot exclude the possibility that TLR4 activation resulted in false-positive hypersensitivity (type 4) to cobalt in the MOM group.…”

Section: Discussionmentioning

confidence: 99%

Metal release and metal allergy after total hip replacement with resurfacing versus conventional hybrid prosthesis

et al. 2014

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BackgroundMetal-on-metal (MOM) total hip arthroplasties were reintroduced because of the problems with osteolysis and aseptic loosening related to polyethylene wear of early metal-on-polyethylene (MOP) arthroplasties. The volumetric wear rate has been greatly reduced with MOM arthroplasties; however, because of nano-size wear particles, the absolute number has been greatly increased. Thus, a source of metal ion exposure with the potential to sensitize patients is present. We hypothesized that higher amounts of wear particles result in increased release of metal ions and ultimately lead to an increased incidence of metal allergy.Methods52 hips in 52 patients (median age 60 (51–64) years, 30 women) were randomized to either a MOM hip resurfacing system (ReCap) or a standard MOP total hip arthoplasty (Mallory Head/Exeter). Spot urine samples were collected preoperatively, postoperatively, after 3 months, and after 1, 2, and 5 years and tested with inductively coupled plasma-sector field mass spectrometry. After 5 years, hypersensitivity to metals was evaluated by patch testing and lymphocyte transformation assay. In addition, the patients answered a questionnaire about hypersensitivity.ResultsA statistically significant 10- to 20-fold increase in urinary levels of cobalt and chromium was observed throughout the entire follow-up in the MOM group. The prevalence of metal allergy was similar between groups.InterpretationWhile we observed significantly increased levels of metal ions in the urine during the entire follow-up period, no difference in prevalence of metal allergy was observed in the MOM group. However, the effect of long-term metal exposure remains uncertain.

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“…Recently it was reported that cobalt ions can activate TLR4 signaling by directly binding to and crosslinking the receptor protein 145 , 146 . The mechanism of cobalt induced TLR4 activation is analogous to that previously described for nickel ions, and is of significance at least for two reasons 14 , 147 .…”

Section: Challengesmentioning

confidence: 99%

Interaction of materials and biology in total joint replacement – successes, challenges and future directions

et al. 2014

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Total joint replacement (TJR) has revolutionized the treatment of end-stage arthritic disorders. This success is due, in large part, to a clear understanding of the important interaction between the artificial implant and the biology of the host. All surgical procedures in which implants are placed in the body evoke an initial inflammatory reaction, which generally subsides over several weeks. Thereafter, a series of homeostatic events occur leading to progressive integration of the implant within bone and the surrounding musculoskeletal tissues. The eventual outcome of the operation is dependent on the characteristics of the implant, the precision of the surgical technique and operative environment, and the biological milieu of the host. If these factors and events are not optimal, adverse events can occur such as the development of chronic inflammation, progressive bone loss due to increased production of degradation products from the implant (periprosthetic osteolysis), implant loosening or infection. These complications can lead to chronic pain and poor function of the joint reconstruction, and may necessitate revision surgery or removal of the prosthesis entirely. Recent advances in engineering, materials science, and the immunological aspects associated with orthopaedic implants have fostered intense research with the hope that joint replacements will last a lifetime, and facilitate pain-free, normal function.

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Metal-on-metal hips: cobalt can induce an endotoxin-like response

Cited by 37 publications

References 8 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?

Metal release and metal allergy after total hip replacement with resurfacing versus conventional hybrid prosthesis

Interaction of materials and biology in total joint replacement – successes, challenges and future directions

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