Swiatkowska, Ilona;
(2019)
Toxicity of metal debris from hip implants.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Hip implants are commonly made of cobalt-chromium and titanium alloys. Once inside the body, implants wear and corrode, releasing metal particles and ions into the local tissue and blood. Metal debris can cause local adverse effects, such as bone loss and tissue necrosis, ultimately leading to implant failure. More recently, systemic cobalt toxicity has gained publicity as reports of neurotoxicity, cardiomyopathy and hypothyroidism increased among recipients of metal hip implants. Widespread dissemination of metal debris, and its accumulation in organ tissue, is of a particular concern. The aim of this thesis is to better understand how metallic implant debris affects the body, and how blood metal levels relate to any toxicity symptoms. Prevalence of neurotoxicity and cognitive decline among patients with a history of highly elevated blood cobalt was assessed, using a set of validated questionnaires. Although a number of statistically significant differences were detected between the high cobalt group and controls, clinically relevant neuro-cognitive adverse effects were not observed. Distribution and chemical speciation of cobalt, chromium and titanium deposits were investigated in cadaveric samples of organs from hip replacement patients. Though synchrotron analysis identified the presence of highly oxidised chromium, further work is needed to assess if the results can be extrapolated to the in vivo situation. Genetic factors that might predispose some patients to the adverse effects of cobalt were explored in vitro, using CRISPR/Cas9 gene editing technology. Results of the feasibility study identified several candidate genes for further investigation. Blood titanium was measured in a large group of patients with titanium-based implants, using high resolution ICP-MS. This allowed a reliable laboratory reference range to be defined for use in future patient monitoring. Results from this thesis inform on potential consequences of implant degradation, and demonstrate the clinical utility of blood metal measurements to monitor implant performance.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Toxicity of metal debris from hip implants |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10085349 |
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