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Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses.

ABSTRACT: Systemic cobalt (Co) and chromium (Cr) concentrations may be elevated in patients with metal joint replacement prostheses. Several studies have highlighted the detrimental effects of this exposure on bone cells in vitro, but the underlying mechanisms remain unclear. In this study, we use whole-genome microarrays to comprehensively assess gene expression in primary human osteoblasts, osteoclast precursors and mature resorbing osteoclasts following exposure to clinically relevant circulating versus local periprosthetic tissue concentrations of Co²⁺ and Cr³⁺ ions and CoCr nanoparticles. We also describe the gene expression response in osteoblasts on routinely used prosthesis surfaces in the presence of metal exposure. Our results suggest that systemic levels of metal exposure have no effect on osteoblasts, and primarily inhibit osteoclast differentiation and function via altering the focal adhesion and extracellular matrix interaction pathways. In contrast, periprosthetic levels of metal exposure inhibit both osteoblast and osteoclast activity by altering HIF-1α signaling and endocytic/cytoskeletal genes respectively, as well as increasing inflammatory signaling with mechanistic implications for adverse reactions to metal debris. Furthermore, we identify gene clusters and KEGG pathways for which the expression correlates with increasing Co²⁺:Cr³⁺ concentrations, and has the potential to serve as early markers of metal toxicity. Finally, our study provides a molecular basis for the improved clinical outcomes for hydroxyapatite-coated prostheses that elicit a pro-survival osteogenic gene signature compared to grit-blasted and plasma-sprayed titanium-coated surfaces in the presence of metal exposure.

SUBMITTER: Shah KM

PROVIDER: S-EPMC8156984 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundProsthetic joint infection (PJI) is a challenging complication of total elbow replacement (TER). Potential surgical treatments include one- or two-stage revision; however, the best treatment for elbow PJI is not clearly defined. We conducted a systematic review in accordance with PRISMA guidelines to compare the clinical effectiveness of one- and two-stage revision surgery for elbow PJI using re-infection (recurrent and new infections) rates; mortality; clinical measures of function, pain, and satisfaction; and non-infection related adverse events.MethodsMEDLINE, Embase, Web of Science, and The Cochrane Library were searched up to June 2019 to identify observational cohort studies and randomised controlled trials (RCTs) that had recruited patients with elbow PJI following TER and treated with one- or two-stage revision. Of 96 retrieved articles, 2 one-stage and 6 two-stage revision studies were eligible. No RCT was identified. Arcsine transformation was used in estimating rates with 95% confidence intervals (CIs).ResultsStaphylococcus aureus was the most common causative organism for PJI of the elbow (24 of 71 elbow PJIs). The re-infection rate (95% CI) for one-stage (7 elbows) ranged from 0.0% (0.0-79.3) to 16.7% (3.0-56.4) and that for two-stage revision (87 elbows) from 0.0% (0.0-49.0) to 20.0% (3.6-62.4). Non-infection related adverse event rate for one-stage (based on a single study) was 16.7% (3.0-56.4) and that for two-stage ranged from 11.8% (4.7-26.6) to 20.0% (3.6-62.4). There were no mortality events recorded following one- or two-stage revision surgery and postoperative clinical measures of function, pain, and satisfaction could not be effectively compared because of limited data.ConclusionsNo strong conclusions can be drawn because of limited data. The one-stage revision may be potentially at least as clinically effective as two-stage revision, but further data is needed. There are clear gaps in the existing literature and studies are urgently warranted to assess the clinical effectiveness of one- and two-stage revision strategies for PJI following TER.Systematic review registrationPROSPERO 2018: CRD42018118002 .

Project description:BackgroundA meta-analysis was performed to evaluate the use of clinical pathways for hip and knee joint replacements when compared with standard medical care. The impact of clinical pathways was evaluated assessing the major outcomes of in-hospital hip and knee joint replacement processes: postoperative complications, number of patients discharged at home, length of in-hospital stay and direct costs.MethodsMedline, Cinahl, Embase and the Cochrane Central Register of Controlled Trials were searched. The search was performed from 1975 to 2007. Each study was assessed independently by two reviewers. The assessment of methodological quality of the included studies was based on the Jadad methodological approach and on the New Castle Ottawa Scale. Data analysis abided by the guidelines set out by The Cochrane Collaboration regarding statistical methods. Meta-analyses were performed using RevMan software, version 4.2.ResultsTwenty-two studies met the study inclusion criteria and were included in the meta-analysis for a total sample of 6,316 patients. The aggregate overall results showed significantly fewer patients suffering postoperative complications in the clinical pathways group when compared with the standard care group. A shorter length of stay in the clinical pathway group was also observed and lower costs during hospital stay were associated with the use of the clinical pathways. No significant differences were found in the rates of discharge to home.ConclusionThe results of this meta-analysis show that clinical pathways can significantly improve the quality of care even if it is not possible to conclude that the implementation of clinical pathways is a cost-effective process, because none of the included studies analysed the cost of the development and implementation of the pathways. Based on the results we assume that pathways have impact on the organisation of care if the care process is structured in a standardised way, teams critically analyse the actual organisation of the process and the multidisciplinary team is highly involved in the re-organisation. Further studies should focus on the evaluation of pathways as complex interventions to help to understand which mechanisms within the clinical pathways can really improve the quality of care. With the need for knee and hip joint replacement on the rise, the use of clinical pathways might contribute to better quality of care and cost-effectiveness.

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Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses.

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