Semi‐quantitative histology confirms that the macrophage is the predominant cell type in metal‐on‐metal hip tissues

Campbell, Patricia A.; Park, Sang-Hyun; Ebramzadeh, Edward

doi:10.1002/jor.25040

Cited by 8 publications

(4 citation statements)

References 31 publications

(72 reference statements)

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“…Terms used in this study were defined to emphasize that MoM reactions represent a spectrum of disease; however, we acknowledge that the manifestation of some of these findings is dependent on the timing of intervention. 27,39,40 In addition, it must be acknowledged that of the 1,171 THAs reviewed only 328 met inclusion criteria with MARS-MRI. Thus, the results of this study must be interpreted in this context, as patients who had MARS-MRIs obtained may have been more likely to have clinical symptomatology concerning for ARMD or PJI.…”

Section: Discussionmentioning

confidence: 99%

The relationship between pseudotumours and infected complications in patients who have undergone metal-on-metal total hip arthroplasty

Leal,

Holland,

Cochrane

et al. 2024

Bone Joint J

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AimsThis study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.MethodsA total of 1,171 total hip arthroplasty (THA) patients with MoM articulations from August 2000 to March 2014 were retrospectively identified. Of those, 328 patients underwent metal artefact reduction sequence MRI and had minimum two years’ clinical follow-up, and met our inclusion criteria. Data collected included demographic details, surgical indication, laterality, implants used, history of pseudotumour, and their corresponding preoperative ESR (mm/hr) and CRP (mg/dl) levels. Multivariate logistic regression modelling was used to evaluate PJI and history of pseudotumour, and receiver operating characteristic curves were created to assess the diagnostic capabilities of ESR and CRP to determine the presence of infection in patients undergoing revision surgery.ResultsThe rate of PJI for all identified MoM THAs was 3.5% (41/1,171), with a mean follow-up of 10.9 years (2.0 to 20.4). Of the patients included in the final cohort, 8.2% (27/328) had PJI, with a mean follow-up of 12.2 years (2.3 to 20.4). Among this cohort, 31.1% (102/328) had a history of pseudotumour. The rate of PJI in these patients was 14.7% (15/102), which was greater than those without pseudotumour, 5.3% (12/226) (p = 0.008). Additionally, logistic regression analysis showed an association between history of pseudotumour and PJI (odds ratio 4.36 (95% confidence interval 1.77 to 11.3); p = 0.002). Optimal diagnostic cutoffs for PJI in patients with history of pseudotumour versus those without were 33.1 mm/hr and 24.5 mm/hr for ESR and 7.37 mg/dl and 1.88 mg/dl for CRP, respectively.ConclusionPatients with history of pseudotumour secondary to MoM THA had a higher likelihood of infection than those without. While suspicion of infection should be high for these patients, ESR and CRP cutoffs published by the European Bone and Joint Infection Society may not be appropriate for patients with a history of pseudotumour, as ESR and CRP levels suggestive of PJI are likely to be higher than for those without a pseudotumour. Additional investigation, such as aspiration, is highly recommended for these patients unless clinical suspicion and laboratory markers are low.Cite this article: Bone Joint J 2024;106-B(6):555–564.

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Section: Discussionmentioning

confidence: 99%

The relationship between pseudotumours and infected complications in patients who have undergone metal-on-metal total hip arthroplasty

Leal,

Holland,

Cochrane

et al. 2024

Bone Joint J

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“…84 In addition, macrophages, similar to fibroblasts, are subject to molecular stochasticity (i.e., they work under molecular signaling as a stochastic process) and cells' spatial organization. 83 Many studies have demonstrated large numbers of activated macrophages in the periprosthetic tissues 61,62,85 as well as their stimuli associated with TJA. [86][87][88][89][90] Thus, there is a large body of evidence supporting a preeminent role for different macrophage populations in the periprosthetic pathologies including a wide-spectrum of foreign-body responses.…”

Section: How Does Chronic Inflammation Affect Periprosthetic Tissues?mentioning

confidence: 99%

Friend or foe? Inflammation and the foreign body response to orthopedic biomaterials

Gibon,

Takakubo,

Zwingenberger

et al. 2023

J Biomedical Materials Res

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The use of biomaterials and implants for joint replacement, fracture fixation, spinal stabilization and other orthopedic indications has revolutionized patient care by reliably decreasing pain and improving function. These surgical procedures always invoke an acute inflammatory reaction initially, that in most cases, readily subsides. Occasionally, chronic inflammation around the implant develops and persists; this results in unremitting pain and compromises function. The etiology of chronic inflammation may be specific, such as with infection, or be unknown. The histological hallmarks of chronic inflammation include activated macrophages, fibroblasts, T cell subsets, and other cells of the innate immune system. The presence of cells of the adaptive immune system usually indicates allergic reactions to metallic haptens. A foreign body reaction is composed of activated macrophages, giant cells, fibroblasts, and other cells often distributed in a characteristic histological arrangement; this reaction is usually due to particulate debris and other byproducts from the biomaterials used in the implant. Both chronic inflammation and the foreign body response have adverse biological effects on the integration of the implant with the surrounding tissues. Strategies to mitigate chronic inflammation and the foreign body response will enhance the initial incorporation and longevity of the implant, and thereby, improve long‐term pain relief and overall function for the patient. The seminal research performed in the laboratory of Dr. James Anderson and co‐workers has provided an inspirational and driving force for our laboratory's work on the interactions and crosstalk among cells of the mesenchymal, immune, and vascular lineages, and orthopedic biomaterials. Dr. Anderson's delineation of the fundamental biologic processes and mechanisms underlying acute and chronic inflammation, the foreign body response, resolution, and eventual functional integration of implants in different organ systems has provided researchers with a strategic approach to the use of biomaterials to improve health in numerous clinical scenarios.

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“…[55] The typical response to metal debris is limited to a macrophage infiltrate. [56] ALVAL is a subset of ARMD, referring to the additional lymphocyte infiltrate and histological features of DTH.…”

Section: Blood/serum Metal Ion Testingmentioning

confidence: 99%

The influence of hla genotype on the development of metal hypersensitivity following joint replacement

Langton¹,

Bhalekar²,

Joyce

et al. 2021

Preprint

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Joint replacement surgery provides pain relief and restoration of mobility for millions of patients around the world each year.[1] However, the release of wear debris from implant surfaces can limit the lifespan of a prosthesis through the promotion of inflammatory responses.[2] Implants must therefore be constructed from materials with sufficient durability and biocompatibility. One such material is cobalt chrome alloy, which is used in the majority of joint replacements.[3] Unfortunately, it is recognised that some patients develop lymphocyte mediated delayed type hypersensitivity (DTH) responses to this material,[4] a response which may result in extensive bone and soft tissue destruction.[5] A genetic predisposition to DTH has been proposed[6], though specific genes have yet to be identified, or the effects quantified. Here we show that variation in HLA class II genotype influences an individual’s susceptibility to DTH. HLA-DQ haplotypes encoding peptide binding grooves with greater affinity for the N terminal peptide sequence of albumin (containing two recognised metal binding sites) confer a greater risk of DTH. We describe the development and validation of a machine learning algorithm to investigate the possibility that a patient’s genotype and basic clinical parameters may be used to predict DTH. Incorporating this novel finding, gradient boosted survival analysis machine learning models were trained and validated using results from 606 patients from three international units. These models were assessed using Uno’s c-index, time-dependent AUROCs, and integrated calibration index performance statistics. At present, there are no tests in widespread clinical use which use a patient’s genetic profile to guide implant selection or inform post-operative management. The algorithm described herein may address this issue.

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Semi‐quantitative histology confirms that the macrophage is the predominant cell type in metal‐on‐metal hip tissues

Cited by 8 publications

References 31 publications

The relationship between pseudotumours and infected complications in patients who have undergone metal-on-metal total hip arthroplasty

The relationship between pseudotumours and infected complications in patients who have undergone metal-on-metal total hip arthroplasty

Friend or foe? Inflammation and the foreign body response to orthopedic biomaterials

The influence of hla genotype on the development of metal hypersensitivity following joint replacement

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