Saturday, July 2, 2011

Systemic effects of metal debris (7M 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.

I said this would be the last in this series however, there seem to be 6 items provided in confidence and I am going to try to locate the source data (more time so I myself would like to take time to review each one daily.

6th and final group of comments from the committee (In confidence data sumbitted by the BIRC)...[6 individual comments provided.. 6-11] 

5 of 6

In a further post-mortem histological evaluation study, metallic wear particles were more prevalant in pateients who had a failed hip arthroplasty compared with patients with a primary hip or knee replacement.

J Bone Joint Surg Am. 2000 Apr;82(4):457-76.

Dissemination of wear particles to the liver, spleen, and abdominal lymph nodes of patients with hip or knee replacement.


Department of Orthopedic Surgery, The Rush Arthritis and Orthopedic Institute, Rush-Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612, USA.



The importance of particles generated by wear and corrosion of joint replacement prostheses has been understood primarily in the context of the local effects of particle-induced periprosthetic osteolysis and aseptic loosening. We studied dissemination of wear particles in patients with total hip and knee replacement to determine the prevalence of and the histopathological response to prosthetic wear debris in the liver, spleen, and abdominal para-aortic lymph nodes.


Postmortem specimens from twenty-nine patients and biopsy specimens from two living patients with a failed replacement were analyzed. Specimens of tissue obtained from the cadavera of fifteen patients who had not had a joint replacement served as controls. The concentration of particles and the associated tissue response were characterized with the use of light microscopy of stained histological sections. Metallic particles were identified by electron microprobe analysis. Polyethylene particles were studied with the use of oil-red-O stain and polarized light microscopy. The composition of polyethylene particles was confirmed in selected cases by Fourier transform infrared spectroscopy and hot-stage thermal analysis. Twenty-one of the patients studied post mortem had had a primary total joint replacement. Eleven of them had had a hip prosthesis for a mean of sixty-nine months (range, forty-three to 171 months), and ten had had a knee replacement for a mean of eighty-four months (range, thirty-one to 179 months). The other eight patients studied post mortem had had a hip replacement in which one or more components had loosened and had been revised. The mean time between the initial arthroplasty and the time of death was 174 months (range, forty-seven to 292 months), and the mean time between the last revision procedure and the time of death was seventy-one months (range, one to 130 months).


Metallic wear particles in the liver or spleen were more prevalent in patients who had had a failed hip arthroplasty (seven of eight) than in patients who had had a primary hip (two of eleven) or knee replacement (two of ten). The principal source of wear particles in the majority of these patients involved secondary nonbearing surfaces rather than wear between the two primary bearing surfaces as intended. In one living patient, dissemination of titanium alloy particles from a hip prosthesis with mechanical failure was associated with a visceral granulomatous reaction and hepatosplenomegaly, which required operative and medical treatment. Metallic wear particles were detected in the paraaortic lymph nodes in 68 percent (nineteen) of the twenty-eight patients with an implant from whom lymph nodes were available for study. In 38 percent (eleven) of all twenty-nine patients with an implant who were studied post mortem, metallic particles had been further disseminated to the liver or spleen, where they were usually found within small aggregates of macrophages occurring as infiltrates without apparent pathological importance. Polyethylene particles elicited a similar response. They were identified in the paraaortic lymph nodes of 68 percent (nineteen) of the twenty-eight patients and the liver or spleen of 14 percent (four) of the twenty-nine patients. The majority of the disseminated wear particles were less than one micrometer in size. Currently available methods lack the sensitivity and specificity necessary to detect very low concentrations of submicrometer polyethylene particles and probably underestimated the prevalence of polyethylene wear debris in the liver and spleen.


In this study, systemic distribution of metallic and polyethylene wear particles was a common finding, both in patients with a previously failed implant and in those with a primary total joint prosthesis. The prevalence of particles in the liver or spleen was greater after reconstructions with mechanical failure.

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