Dataset Information

Wear of hip prostheses increases serum IGFBP-1 levels in patients with aseptic loosening.

ABSTRACT: The biological mechanisms involved in aseptic loosening include inflammation-associated and bone resorption-associated processes. Coordinated cellular actions result in biochemical imbalances with devastating consequences for the joint. Given that this condition is not known for showing systemic signs, we investigated whether circulating levels of inflammation-related proteins are altered in patients with aseptic loosening. Our study included 37 patients who underwent revision surgery due to hip osteolysis and aseptic loosening and 31 patients who underwent primary total hip arthroplasty. Using antibody arrays, we evaluated the serum levels of 320 proteins in four patients from each group. The results showed differences in insulin-like growth factor-binding protein 1 (IGFBP-1) concentrations, which we then quantified using enzyme-linked immunosorbent assay tests in all study patients. The results confirmed that serum IGFBP-1 concentrations were higher in the revision surgery patients than in the hip arthroplasty patients. In vitro studies showed that exposure of human osteoblasts to titanium particles induced an IGFBP-1 release that further increased when exposure to particles was performed in media conditioned by human M1 macrophages. These findings suggest that elevated serum IGFBP-1 levels in patients with aseptic loosening can arise from increased local IGFBP-1 production in the inflammatory environment of the periprosthetic bed.

SUBMITTER: Valles G

PROVIDER: S-EPMC7804331 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Wear of hip prostheses increases serum IGFBP-1 levels in patients with aseptic loosening.

Vallés Gema G García-Rey Eduardo E Saldaña Laura L García-Cimbrelo Eduardo E Vilaboa Nuria N

Scientific reports 20210112 1

The biological mechanisms involved in aseptic loosening include inflammation-associated and bone resorption-associated processes. Coordinated cellular actions result in biochemical imbalances with devastating consequences for the joint. Given that this condition is not known for showing systemic signs, we investigated whether circulating levels of inflammation-related proteins are altered in patients with aseptic loosening. Our study included 37 patients who underwent revision surgery due to hip ...[more]

PMID: 33436773

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Project description:BackgroundAseptic loosening (AL) of hip prosthesis presents inflammation and pain as sign and symptom similarly to arthritis pathologies. Still, the immune and innervation profiles in hip AL remain unclear and their interplay is poorly explored. Herein, local tissue inflammatory response, sensory and sympathetic innervation as well as associated local mediators were assessed in hip joint microenvironment underlying AL and compared to osteoarthritis (OA).MethodsHistopathological analysis, immune cells (macrophages, T, B cells and PMNs) as well as sensory and sympathetic nerve fibers (SP(+), CGRP(+), TH(+)) distribution and profiles were analyzed on tissues retrieved from patients with failed hip prostheses due to AL (n = 20) and hip OA (n = 15) by immunohistochemistry. Additionally, transcriptional levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-12a, iNOS), anti-inflammatory cytokine (IL-10), osteoclastic factor (RANKL) and bone remodeling factor (TGF-β1) were locally evaluated by qRT-PCR. Serum TGF-β1 levels were assessed preoperatively by ELISA.ResultsHistopathological analysis revealed that tissues, aseptic interface membranes of AL patients had distinct tissue architecture and immune cells profile when compared to OA synovial tissues. Macrophages, T cells and B cells showed significant differences in tissue distribution. In OA, inflammation is mostly confined to the vicinity of synovial membrane while in AL macrophages infiltrated throughout the tissue. This differential immune profile is also accompanied with a distinct pattern of sensory and sympathetic innervation. Importantly, in AL patients, a lack of sympathetic innervation aseptic interface membranes without compensation mechanisms at cellular levels was observed with simultaneous reorganization of sensorial innervation. Despite the different histopathological portrait, AL and OA patients exhibited similar transcriptional levels of genes encoding key proteins in local immune response. Nevertheless, in both pathologies, TGF-β1 expression was prominent in sites where the inflammation is occurring. However, at systemic level no differences were found.ConclusionThese findings indicate that AL patients exhibit different local inflammatory response and innervation signatures from OA patients in hip joint. These insights shed the light on neuro-immune interplay in AL and highlight the need to better understand this crosstalk to unravel potential mechanisms for targeted-therapies to improve hip joint lifetime and treatment.

Project description:BackgroundMetal-on-Metal (MoM) total hip arthroplasties (THA) are associated with pseudotumor formation and high revision rates. This prospective study analysed the clinical and wear analyses of 9 large Metal-on-Metal (MoM) total hip arthroplasties (THA) to understand the underlying mechanisms of failure. The MoM bearings were revised for multiple reasons; the main reason was pseudotumor formation.Materials and methodsFrom 2006 till 2010 the Reinier de Graaf Hospital implanted 160 large head M2a-Magnum™ (Biomet Inc. Warsaw, Indiana, USA) THAs in 150 patients. The first year, 9 bearings were revised and analysed at the Biomechanics Section, Hamburg University of Technology, Germany. We performed clinical (Harris Hip Score, radiographic analysis, blood cobalt and chromium) and wear analysis (implant, tissue and fluid) of the 9 bearings. Since this study did not fall under the scope of the Medical Research Involving Human Subjects Act in The Netherlands, no ethical approval was necessary. In this prospective study all patient details were anonymized by the corresponding author, all other authors were blinded during the research and wear analyses. Patients with bilateral MoM implants were excluded.ResultsThe 9 bearings had a median (IQR) survival of 41.0 (25) months in situ. From these bearings, three showed no noticeable wear. The median (IQR) head wear volume was 3.2 (3.6) mm3 and maximum wear depth 0.02 (0.02) mm. For the cup the median (IQR) wear volume was 0.23 (0.3) mm3 with a maximum wear depth of 0.03 (0.05) mm.ConclusionAn early identification of parameters related to failure of the MoM THA, such as pain, decreased range of motion, radiographic changes and high levels of blood cobalt and chromium is of great importance for patient's quality of life. Especially now patients and surgeons face the long term effects of all these bearings still in situ. This study reports the clinical and wear analyses of 9 MoM THA. In the majority of this group the reason for revision was pseudotumor formation. Most bearings showed signs of wear, however with a great diversity in clinical analysis, in inclination angle, serum cobalt and chromium levels as well as wear analysis. For a better understanding of the underlying mechanisms related with failure, more wear analyses of revised MoM bearings are necessary as well as a frequent follow-up of the patients with a MoM bearing.

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Wear of hip prostheses increases serum IGFBP-1 levels in patients with aseptic loosening.

Publications

Wear of hip prostheses increases serum IGFBP-1 levels in patients with aseptic loosening.

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