Thursday, June 23, 2011

Systemic effects of metal debris (7g of 7); excerpts from the Committee on Mutagenicity

Excerpts and commentary based on the 6/4 post-Metal on Metal Bearings, The Evidence So Far

Genotoxic issues surrounding systemic effects of metal debris (continued from prior posts)

The committee on mutagenicity has reported that internal exposure to orthopedic metals is associated with increased genotoxicity.

This is a series of commentary from the committee on mutangenicity evidence based on the the key journal articles examined by that committee. I think you will find the results really interesting if you are concerned about the systemic effects of the metal.

4th piece of evidence reviewed by the committee:

J Bone Joint Surg Br. 2004 May;86(4):598-606.

Wear debris from hip or knee replacements causes chromosomal damage in human cells in tissue culture.


Bristol Implant Research Centre, Avon Orthopaedic Centre, Southmead Hospital, Bristol, England, UK.


Wear debris was extracted from 21 worn hip and knee replacements. Its mutagenic effects were tested on human cells in tissue culture using the micronucleus assay and fluorescent in situ hybridisation. The extracted wear debris increased the level of micronuclei in a linear dose-dependent manner but with a tenfold difference between samples. The concentration of titanium +/- vanadium and aluminium within the wear debris was linearly related both to the level of centromere-positive micronuclei in tissue culture, indicating an aneuploid event, and to the level of aneuploidy in vivo in peripheral blood lymphocytes. The concentration of cobalt and chromium +/- nickel and molybdenum in the wear debris correlated with the total index of micronuclei in tissue culture, both centromere-positive and centromere-negative i.e. both chromosomal breakage and aneuploidy events. The results show that wear debris can damage chromosomes in a dose-dependent manner which is specific to the type of metal. The results from studies in vitro correlate with those in vivo and suggest that the wear debris from a worn implant is at least partly responsible for the chromosomal damage which is seen in vivo.

What the committee concluded:

  • It was agreed that the magnitude of response was relatively small and was suggestive of an effect at the top dose level.  However, overall, this study had not provided convincing evidence of a metal specific effect.

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