The effects of clinically relevant concentrations of metal ions after hip replacement on bone cell physiology.

Authors: Karan Shah (University of Sheffield)
Co-authored by industrial partner: No

Type: Thesis

State: Published (Approved)
Published: April 2014
Diamond Proposal Number(s): 4354 , 6831

Abstract: In the last decade, metal-on-metal (MOM) hip replacements have been a popular alternative to conventional total hip arthroplasty (THA) in younger more active patients requiring hip replacement surgery, due to their improved wear and lubrication characteristics. However, these prostheses have a relatively poor clinical outcome compared to THA. The most frequent reasons for failure include osteolysis, aseptic loosening, femoral neck fracture and periprosthetic inflammatory masses attributed to the adverse local tissue reactions to metal ions and particles released from the prosthesis. More recently, similar adverse events have been associated with modular conventional hip implants due to corrosion and wear at metal junctions. Most implants rely on good periprosthetic bone health for fixation and survival. This warrants the understanding of the effects of prostheses related metal ions and particles on bone cell survival and function. This project investigates the effects of clinically relevant concentrations and combinations of metal ions (Co2+, Cr3+ and Cr6+) on survival and function of osteoblasts, osteoclasts and osteocytes. Furthermore, it describes the intracellular distribution and speciation of metal ions in bone cells and investigates the possible mechanisms of their cellular entry. The results from this group of studies suggest that in the local periprosthetic environment, there is inhibition of bone cell activity with implications for primary fixation of the implant and its survivorship. Over a narrow systemic concentration range, the metal ions increased osteoblast differentiation and mineralisation, consistent with a small increase in bone mineral density observed clinically. The results of sub-cellular distribution suggest different mechanisms of cellular entry for metal ions based on the cell type and stage of differentiation, whilst the speciation data confirms the intracellular reduction of Cr6+, with no change in oxidation stage observed for Co2+ and Cr3+. Furthermore, the cellular entry of Co2+ was reduced with P2X7R antagonist in osteoblasts but not osteoclasts, offering a cell specific therapeutic target to alter bone remodelling in the periprosthetic environment. The main limitation of the study was the use immortalised cell-lines which, whilst being convenient and useful tool, may not accurately represent the clinical setting.

Subject Areas: Medicine, Biology and Bio-materials, Technique Development

Instruments: I18-Microfocus Spectroscopy

Added On: 12/09/2014 09:26

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