Monday, July 4, 2011

Summary of the Systemic issues dicussed from 7a-7n/14 articles considered by the committee on mutagenicity

We have considered 14 references provided by the committee on mutagenicity.  I published them all but one which at the time, I couldn't locate the reference but have it now and will include it at the bottom of this document.

The committee reached the following conclusions:  [Connie's comments in brackets]

1. Overall, the committee agreed there was GOOD EVIDENCE FOR AN ASSOCIATION BETWEEN chromium Cobalt on Chromium Cobalt (short for metal on metal) or Titanium on Poly hip replacements and genotoxicty in patients. It does not neciessarily mean there is a causal relation.

[While there is good evidence, it doesn't necessarily mean the metal causes cancer but it doesn't mean that it does not cause cancer either.]

[In genetics genotoxicity describes a deleterious action on a cell's genetic material affecting its integrity. Genotoxic substances are known to be potentially mutagenic or carcinogenic, specifically those capable of causing genetic mutation and of contributing to the development of tumors]

2.  The possibility of interactions between metal ions with regard to mutagenic effects could not be discounted.

[In genetics, a mutagen (Latin, literally origin of change) is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations cause cancer, mutagens are typically also carcinogeic.]

3.  There was no convincing evidence for increased genotoxicity in patients with stainless steel on poly hip replacements.

4.  It was not possible to make any definite conclusions as to which metal ions or interactions between metal ions or particulate metals might be responsible for the observed genotoxity.

[As stated previously, identifying which metals ions might be responsible for the observed geneotoxicty can be answered by the investigators if the committee bothered to ask.  That answer should reside in the data used for the journal articles.  The issue here is that there is good evidence for MoM hips and genotoxicty.]

5.  There was limited evidence available to suggest a possible interaction between Cr Co ions and and possible mutagenicty/DNA damage in vitro (test tube environment) but not in vivo (in living organism).
[ My comments to this:
  • I would not consider the 14 documents above limited evidence.
  • It's pretty interesting that anyone viewing the Jenkin article which I will summarize below as in vitro vs in vivo  evidence. Maybe this is my mistake but it looks to me like this whole study was conducted with live patients who had hip replacements!
  • The investigators seemed to report evidence  that there was an increase in lymphocytes in the blood from patients both with primary and revision hip surgery with metal implants  found in patients with non Hodgkin's lymphoma. 
Detection of T (14;18) translocations in periperal blood lymphocytes from patients with total hip atheroplasty
Jenkins L et al, J of Bone and Joint Surgery, 81B (suppl III), 319, 1999.

1.  Some epidemiological studies suggest that there is an increased risk of lymphoma and leukemia in patients with total hip atheroplasty in situ for more than 10 years.

2.  Wear debris including the potential carcinogens of chromium and nickle accumulate at the highest concentrations in the lymph nodes and in the bone marrow.

3.  A cytogenic study has shown a higher chromosomal aberration rate in bone marrow cells adjacent to the prosthesis at revision surgery compared to the bone marrow of the primary hip replacement.

4.  Furthermore, 2 of the 21 patients at revision surgery (implant in situ for more than 10 years) demonstrated colonal expansion of lymphocytes in the blood.

5. This study was performed to see if there was an increased frequency of the mtuagentic marker in patients with primary vs revision surgery.

6.  T (14;18) translocations is characteristic of non hodgkins lymphoma.

7.  Peripheral blood samples were obtained pre op from both the first time hip patients as well as the revisions.

8.  Preliminary data suggests that the T (14;18) translocation frequency is higher in patients with revisions (37% were positive) than those undergoing primary hip replacements (22% were positive). 

9  Further study will involve the correlation of the T (14;18) results and clinical data and metal analysis.

[ I think this is a pretty convincing article along with some of the other articles discussed in this series that the issue of cancer being linked to MoM hip replacements is far from a solved issue.  I think this is an open issue that requires further investigation and funding....that should be seriously funded (not token funding) through the settlement from the Depuy hip law suit.  Funding this research should be a MUST HAVE in any settlement.
 It seems to me that the data published here in the last 14 studies clearly indicates  that there is more than a reasonable possibility that MOM hips can be tied to cancer with some further work.  These studies are quite convincing to me that there are in fact DNA alterations that result from MoM replacements.

So, what  the heck happened with the study above?  Have these guys published more work on this?  If no, why not?  If yes, why isn't mentioned in the original document published on :  Evidence thus far? I will put on my to do list.]




I will include the 3 references for this last article because in the third one, the tests were explained that measured the T (14;18) translocations which I intend to ask my surgeon about.  No reason he can't run these tests if they have been run before.

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