Monday, February 28, 2011

Acute and chronic systemic chromium toxicity (1 of 8 on Chromium toxicity)

G.D. Searle & Co., Skokie, IL 60077.
Erratum in:
  • Sci Total Environ 1990 Jun;95:295.

Abstract

Although chromium and compounds containing it have been recognized as having potential severe adverse effects on health for more than 160 years, understanding of the systemic toxicology and true hazard of these compounds is still not complete. A review of the current state of knowledge is attempted in this paper, with appropriate attention given to the complications of multiple valence states and solubility. Selected chromium compounds, particularly hexavalent ones, are carcinogens, corrosives, delayed contact sensitizers, and have the kidney as their primary target organ. But chromium is also an essential element for humans. The body clearly possesses some effective detoxification mechanisms for some degree of exposure to hexavalent chrome compounds. The significant features of acute and chronic chromium toxicity are presented in view of these considerations.

What is this audience interested in hearing about?

I have been reviewing the traffic of the past posts.  It seems as though the highest peak traffic during the months occur when I post information from the science abstracts in a particular interest area.  The traffic was quite high during the posts on Ion Toxicity so that would indicate that I should continue to post various abstract summaries from my research.

In this upcoming series, I will post abstracts on chromium toxicity as it effects the kidneys.  Most of the studies in this area are based on environmental exposure though.  I will post the first one tonite.

Please do let me know if you would like to hear about certain issues.  There are 8 nice abstracts on chromium toxicity and a few on cobalt toxicity (8 on chromium and 4 on cobalt.)

Remember that the hip prosthesis is made from a trivalent chromium and most (not all) chromium toxicities are from the hexivalent chromium or chromium 6 rather than chromium 3. 


Connie

Sunday, February 27, 2011

Interesting Youtube animation hip surgery videos

Interesting Videos on Youtube re the hip surgery, ion toxicity etc with very nice animation which were done independently by MediaVisuals (http://www.medivisuals.com/).  I found the animations visually informative.  There is no voice over but the animations themselves are very nicely executed.
http://www.youtube.com/watch?v=YrSmlwNWAmQ&feature=mfu_in_order&list=UL

Saturday, February 26, 2011

My visit to the Nephrologist resulted in some interesting information with respect to the role of the kidney with metal toxicity.

A Nephrologist is a doctor specializing in the kidney.  The kidney is the main “filter” in your body for getting rid of things that your body doesn’t need.  They serve the body as a natural filter of the blood, and remove wastes which are diverted to the urinary bladder. In producing urine, the kidneys excrete wastes.  Chromium and cobalt would be considerd to be waste so the kidney function is important with respect to eliminating this toxic waste.
For those of you who have followed this blog, you know that I have been interested in uncovering the issues surrounding nehrotoxicity (kidney toxicity) due to the elevated Cr and Co levels in the body from the hip replacement.  My concerns are a result of having only one kidney remaining and Chromium toxicity has been known to "target" the kidneys. 
Topics which came up in this conversation:
(1)    Many of the studies conducted re Chromium and Cobalt toxicity are environmentally based.  That is, exposure has come from your surrounding environment…. Not from the metal exposure in your body.
(2)     The nephrologist thought that the kidney might be the last organ in the body to be affected by the Cr and Cobalt. 
(3)    Likely the levels of metals would be high in the kidney since it is responsible for excreting unwanted toxins.
(4)    She did not know what level of these metals could be handled by the kidney and didn’t think anyone knew.  She felt that there was not enough work done in the area of metal toxicity resulting from implants.
(5)    She explained how a  properly functioning kidney could be identified .
a.       One of the better tests to determine whether your kidney is properly filtering body waste is to run a 24 hour urine.  While the test is a bit of a pain to run (you have to collect all of your urine output over 24 hours), it is the best  initial test to indicate proper functioning (vs just a sample urine test.)
b.      I was happy to learn that despite my missing one kidney, my kidney function was very good.  My levels (of creatinine) were normal in the 80s.  People who are experiencing kidney failure have levels in the 10% range. (I think I got this right but can’t be sure!) While I was not concerned with kidney failure, I was concerned about overtaxing this organ.  At least this organ is not being “overtaxed” now.  Who knows what the implication is over time.  No one knows.
(6)    The organs she felt might be of more immediate risk were the liver, spleen and lymph nodes.  Recall that the last study I published last week in fact was this one:
Dissemination of wear particles to the liver, spleen, and abdominal lymph nodes of patients with hip or knee replacement
(7)   None of the questions I raised a few days ago in the blog could be answered.  She said there is no data available to answer the questions. (I may print the key abstracts from these articles as they provided additional indicators as to how the kidneys could be affected from these metal ions.)
Connie

Friday, February 25, 2011

Tip From Depuy

Don't forget to abstain from vitamins 3 days prior to taking your toxicity tests for Cr and Co. Failing to do so might result in elevated levels.

Connie

Thursday, February 24, 2011

Implications of Ion Toxicity on the kidneys (Questions that must be answered.)

Those of you follow this blog know I have been wrestling with the questions surrounding the potential harmful effects the ion toxicity levels may have on kidneys since I have only one remaining.  Tomorrow, I have an appointment with a nephrologist (kidney specialist) to shed some light on these questions. I thought I might share them with you.
Questions for my consults (in no particular order):
1)      What is the cancer risk in  the kidney given the statistically significant results found in the Sweden study?
2)      What is the risk of a trivalent chromium being a carcinogen with the primary target being the kidney?
3)      Kidney epithelial cells are 10x more sensitive towards Cr 6 than the same liver cells. Humm hepatoxic issues as well ?
4)      Can non toxic Cr3 be oxidized to Cr 6 under certain conditions and what are they? (very important question/studies indicate yes.)
5)      What is the toxic range for Cr and Co in the kidney?
6)      What are the signs for this?
7)      What are the tests for measuring the accumulation of these metals in the kidneys?
8)      What is my risk given I have only one left?
9)      What is the risk differentiator with metal implants vs inhaled or oral exposure? Studies seem to be focused on the latter not the former?
10)   What are the genotoxic effects for a trivalent Cr to the kidney?
11)   What oxidation is this metal exposed to in the body once it is in there?
12)   What solubility issues should be considered?
13)   Once absorbed, Cr 6 IS QUICKLY REDUCED TO THE TIRVALENT FORM WHICH ACCOUNTS FOR ALL OF THIE ELEMENT PRESENT IN THE BLOOD STREAM OR TAKEN UP BY THE TISSUE?  What??  Then how is CR 6 responsible for cancer and other things if it is non toxic?
14)   How is this absorbed by the kidney?
15)   Two main features of kidney damage re metals: (Is this correct overall?)
a.       Lack of dose-effect/response relationships or progression toward more severe impairment when the exposure intensity increases
b.      The recent absorption rate more than the cumulated does is responsible for the observed nephrotoxic effects.
16)   What is renal oligio anuric deficiency?  How is it caused?
17)    There is good evidence that Cr 6 is the ion responsible for MOST of the toxic actions although much of the underlying molecular damage may be due to the intracellular reduction to the even more highly reactive and short-lived Cr3 and Cr6. ??
18)   What about Cobalt?  “Patients with impaired renal function may experience Co poisoning without the presence of pain despite a well positioned implant because the cobalt released by normal implant wear is not adequately cleared by their kidneys? (2010/Alaska epidemiology)
19)   In short term tests, the hexavalent Cr demonstrated genotoxic effects 4 times more frequently than did the trivalent Cr compounds.  Well this is not comforting. This tells me that there are geneotoxic effects with trivalent as well.  So what are they?

Wednesday, February 23, 2011

Causes of Actions filed agaist Depuy

Causes of action asserted in the filed class actions against Depuy
·         Negligence
·         Strict Products Liability
o   Manufacturing defect
o   Design defect
o   Inadequate warning
o   Failure to conform to representations
o   Failure to adequately test
·         Breach of express warranty
·         Breach of Implied warranty of merchantability
·         Fraudulent concealment
·         Intentional misrepresentation
·         Unlawful, unfair and fraudulent business practices
Additional causes of action asserted in the filed individual complaints against Depuy
·         Negligent misrepresentation
·         Unjust enrichment
·         Negligent infliction of emotional distress
·         Strict products liability
o   Failure to warn and instruct

Tuesday, February 22, 2011

Hip Implant Recall Takes Spotlight at annual convention of the American Academy of Orthodpedic Surgeons

Thousands of orthopedic surgeons from around the world are meeting in San Diego this week for the annual convention of the American Academy of Orthopedic Surgeons. Not surprisingly, the recent DePuy hip replacement recall, as well as other metal-on-metal implants like the DePuy Pinnacle hip implant, are hotly discussed topics among the doctors who are attending the convention.

Dr. Thomas Schmalzried, one of the designers of the recalled DePuy ASR hip implant, is scheduled for several presentations regarding metal-on-metal implants. One of these sessions is titled: “Metal-Metal Articulation: Implants: Is It Worth The Risk.”

Monday, February 21, 2011

My appointments with specialists seem to result in more questions than answers.

This week, I went to NYC in order to get the most advanced radiological protocol used to determine the exact damage to my hip and surrounding areas.  The Test was an MRI using the Mavrick protocal.   As I have mentioned in previous posts, I have no consistent pain nor is my implant loose.  My primary concern has been and continues to be my ion levels given I have only one remaining kidney. 



Chromium Blood ion test taken on 1/4/11
Cobalt blood ion test taken on 1/4/11
24 hour Urine chromium test taken on 1/30/11
Other Urine chromium test taken on 1/30/11
Cobalt Urine test taken on 1/30/11
2nd blood chromium test taken on 2/9
2nd blood cobalt test taken on 2/9
Actual result
28mcg/l
34 mcg/l
86
49
> 10.0 ug/l
21.6 ug/l
29.5 ug/l
Reported normal level
<2mcg/l
<1.8mcg/l
.6
.5
.1-.2
.5 ug/l
<1ug/l
Multiple over normal
14x
18.8x
143x
98x
5-100 x
43.2x
30x

Radiologist’s observations (preeminent in her field of orthopedic MRIs as a diagnostic tool):
·         Osteolysis exists.  Enlarged iliac lymph nodes and decompression of the wear-induced synovitis creating a collection of metal induced synovitis is found  in the bursa.  The gluteus medius is degenerated and there is a partial tear of the gluteus minimus and degeneration of the hamstring origin.  There is no indication of infection and the devise is not loose.
·         The radiologist is not an expert in the ion toxicity but absent the ion issues, she would likely not replace the hip
2nd opinion from an orthopedic surgeon specializing in revisions:
·         He felt that given I had only one kidney remaining, I should not have been given a  MOM implant to begin with albeit, he is not now nor has he ever been and advocate of MOM implants.  He uses very few in his practice.
·         He said the surgeon who implanted the device was highly skilled and positioned the implant to a near perfected state.  (That was good news but if the toxicity comes from the abrasion between the two metals mostly due to surgical error in implanting them, and my surgeon did a great job with the implant,  why are my chemical levels so high?  I question this whole theory of the MoM rubbing against each other being the main cause these toxic chemical levels.)
·         He suggested that I get a really good university based nephrologist (Kidney expert) to assess the issues with the toxicity and my kidney.
·         His suggestion was to recheck the levels again in 6 months.  He clearly said if the metal levels are 5x normal levels, it was cause for concern.  My levels are way beyond that.
My next steps:
·         Consult with the specialist in metal toxicity
·         Consult with a nephrologist.
Connie

Sunday, February 20, 2011

What seems to be the bottom line in the 14 or 15 Ion Toxicity research abstracts printed over the last 7 days?

These abstracts of the clinical work are cited most often when this subject is discussed.  Note that the date range of these journal articles is from 1995-2002. Bottom line comments from all of the studies I published covered only up to  2002:
·         “Our results do not support previous suggestions of an increased incidence of leukemia and lymphoma after total hip replacement.”
·         “The overall relative risk of cancer was increased by only 3%....but not statistically significant”
·         “The small but statistically significant increases in kidney and prostate cancers and the decrease in gastric cancer deserve further study.”
·         “The observed variation in the incidence of different cancers among patients who had total hip arthroplasty compared with the general population suggests that factors other than total hip arthroplasty play a major role in the origin of cancer”
·         “Although the toxicologic importance of these trace metal elevations has not been established, serum and urine metal concentrations may be useful markers for the tribologic performance of metal on metal bearings.”
·         “The serum and urine cobalt concentrations were below the detection limit in all patients.”
·         “The values seen in this study with the current generation of surface arthroplasties are: (a) lower than those seen in an earlier generation of surface arthroplasties; (b) in the same range as those observed in association with metal-on-metal conventional total hip replacements, which typically have smaller head sizes; (c) higher than values observed in patients with conventional metal-on-polyethylene articulating couples.”
·         “The association of metal release from orthopaedic implants with any metabolic, bacteriologic, immunologic, or carcinogenic toxicity currently remains conjectural because cause and effect have not been established in human subjects. However, continued surveillance of patient populations with metal implants, particularly those with metal-metal bearings, is warranted.”
·         “As compared with metal on polyethylene cases, the extent of the granulomatous inflammatory reaction and the presence of foreign body type giant cells was much less intense in metal on metal cases, likely because of the lower numbers and overall smaller size of metal wear debris particles.”
·         “….. protein binding is initiated in the periprosthetic space where metal concentrations are typically 2-3 orders of magnitude higher than that observed systemically in the serum. In vitro, high molecular weight proteins including immunoglobulins demonstrated the highest affinity to Cr. Determination of specific protein carriers of metal degradation products is an essential component in the assessment of the long-term biological effects of total joint replacement devices
·         “A multi-assay approach for measuring the prevalence of delayed-type hypersensitivity in orthopedic patients shows the propensity to yield a more comprehensive and, therefore, more conclusive determination than currently employed patch testing or single assay techniques.”
·         “A multi-assay approach for measuring the prevalence of delayed-type hypersensitivity in orthopedic patients shows the propensity to yield a more comprehensive and, therefore, more conclusive determination than currently employed patch testing or single assay techniques.”
·         “Until the roles of delayed hypersensitivity and humoral immune responses to metallic orthopaedic implants are more clearly defined, the risk to patients may be considered minimal. It is currently unclear whether metal sensitivity is a contributing factor to implant failure.”
·         “This in vitro study demonstrated a lymphocyte proliferative response to both Co-Cr-Mo and Ti alloy metalloprotein degradation products. This response was greatest when the metals were complexed with high molecular weight proteins, and with metal-protein complexes formed from Co-Cr-Mo alloy degradation.”
·         “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.

If I understood these articles,  I don’t hear any definitive conclusions about the cause and effect these hip implants seem to have systemically on the organs.  I think there is enough suspicion however to defiantly warrant additional study. I also wonder why the organs of implant patients are not sampled for metal levels in autopsies.  Some have been conducted but not enough.  The studies I found most interesting in raising questions were the 2000 Article By Josh Jacobs MD et al re the wear particles in the spleen, liver and lymph nodes were higher with a failed hip.  The study done in Sweden on the statistically significant increase in Kidney and prostate cancers.
 I will look at the recent Josh Jacobs papers to see if anything has happened since 2002 worth mentioning.  

Connie 

Friday, February 18, 2011

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

J Bone Joint Surg Am. 2000 Apr;82(4):457-76.
Department of Orthopedic Surgery, The Rush Arthritis and Orthopedic Institute, Rush-Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612, USA. rurban@rush.edu
Comment in:

Abstract

BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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. (ABSTRACT TRUNCATED)

Orthopaedic implant related metal toxicity in terms of human lymphocyte reactivity to metal-protein complexes produced from cobalt-base and titanium-base implant alloy degradation. (ion Toxicity 14 of 14)

Mol Cell Biochem. 2001 Jun;222(1-2):127-36.
Department of Orthopedic Surgery, Rush-Presbyterian-St. Lukes Medical Center, Chicago, IL, USA.

Abstract

Metal toxicity from sources such as orthopaedic implants was investigated in terms of immune system hyper-reactivity to metal implant alloy degradation products. Lymphocyte response to serum protein complexed with metal from implant alloy degradation was investigated in this in vitro study using primary human lymphocytes from healthy volunteers (n = 10). Cobalt chromium molybdenum alloy (Co-Cr-Mo, ASTM F-75) and titanium alloy (Ti-6Al-4V, ASTM F-136) beads (70 microm) were incubated in agitated human serum at 37 degrees Celsius to simulate naturally occurring metal implant alloy degradation processes. Particulate free serum samples, which were incubated with metal, were then separated into molecular weight based fractions. The amounts of soluble Cr and Ti within each serum fraction were measured and correlated with lymphocyte proliferation response to the individual serum fractions. Lymphocytes from each subject were cultured with 11 autologous molecular weight based serum fractions either with or without added metal. Two molecular weight ranges of human serum proteins were associated with the binding of Cr and Ti from Co-Cr-Mo and Ti implant alloy degradation (at < 30 and 180-330 kDa). High molecular weight serum proteins (approximately 180 kDa) demonstrated greater lymphocyte reactivity when complexed with metal released from Co-Cr-Mo alloy and Ti alloy than with low (5-30 kDa) and midrange (30-77 kDa) serum proteins. When the amount of lymphocyte stimulation was normalized to both the moles of metal and the moles of protein within each fraction (Metal-Protein Complex Reactivity Index, MPCRI), Cr from Co-Cr-Mo alloy degradation demonstrated approximately 10 fold greater reactivity than Ti in the higher molecular weight serum proteins (approximately 180-250 kDa). This in vitro study demonstrated a lymphocyte proliferative response to both Co-Cr-Mo and Ti alloy metalloprotein degradation products. This response was greatest when the metals were complexed with high molecular weight proteins, and with metal-protein complexes formed from Co-Cr-Mo alloy degradation.

Metal sensitivity in patients with orthopaedic implants. (Ion Toxicity 13 of 14)

J Bone Joint Surg Am. 2001 Mar;83-A(3):428-36.
Department of Orthopaedic Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. nhallab@rush.edu

Abstract

All metals in contact with biological systems undergo corrosion. This electrochemical process leads to the formation of metal ions, which may activate the immune system by forming complexes with endogenous proteins. Implant degradation products have been shown to be associated with dermatitis, urticaria, and vasculitis. If cutaneous signs of an allergic response appear after implantation of a metal device, metal sensitivity should be considered. Currently, there is no generally accepted test for the clinical determination of metal hypersensitivity to implanted devices. The prevalence of dermal sensitivity in patients with a joint replacement device, particularly those with a failed implant, is substantially higher than that in the general population. Until the roles of delayed hypersensitivity and humoral immune responses to metallic orthopaedic implants are more clearly defined, the risk to patients may be considered minimal. It is currently unclear whether metal sensitivity is a contributing factor to implant failure.

Thursday, February 17, 2011

A triple assay technique for the evaluation of metal-induced, delayed-type hypersensitivity responses in patients with or receiving total joint arthroplasty. (Ion toxcity 12 of 14)

J Biomed Mater Res. 2000 Sep;53(5):480-9.
Department of Orthopedic Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. nhallab@rush.edu

Abstract

The determination of biocompatibility has been dominated historically by the characterization of candidate materials based upon the observation of adverse host responses. However, some adverse responses are subtle in clinical settings and continue to foster debate and investigation. One of these responses is "metal allergy" or hypersensitivity to metallic biomaterials. Current methods used to diagnose hypersensitivity reactions, such as dermal patch testing and migration inhibition assays, are not well accepted in orthopedic practice as a means for the characterization of hypersensitivity to metallic joint-replacement components. An increasing need to resolve whether metal sensitivity may be a significant and/or predisposing factor for eliciting an over-aggressive immune response in patients with metallic implant components requires improved and standardized widespread study. Here we present three in vitro methodologies: (1) a proliferation assay, (2) cytokine analysis using ELISA, and (3) a migration inhibition assay. When in conjunction with one another, these assays may be used to more comprehensively quantify metal-induced hypersensitivity responses. Therefore, these methodologies are detailed with the intent of facilitating multi-center large-scale studies. In the following cases, a multi-assay approach for measuring the prevalence of delayed-type hypersensitivity in orthopedic patients shows the propensity to yield a more comprehensive and, therefore, more conclusive determination than currently employed patch testing or single assay techniques.

Systemic metal-protein binding associated with total joint replacement arthroplasty. (Ion toxicity 11 of 14)

J Biomed Mater Res. 2000 Mar 5;49(3):353-61.
Department of Orthopedic Surgery, Rush-Presbyterian-St. Lukes Medical Center, 1653 West Congress Avenue, Chicago, Illinois 60612, USA. nhallab@rush.edu

Abstract

The distribution of titanium [Ti] and chromium [Cr] in serum protein fractions of patients with and without total joint replacements containing Cr and Ti was studied. Three groups were evaluated: 10 patients with cobalt-chromium [CoCr] alloy prostheses and known elevated levels of Cr; 10 patients with Ti containing implants and known elevated levels of Ti; and 10 age matched controls without prostheses. Metal-protein binding was also examined by adding various concentrations of Cr(+3) (CrCl(3)) to control serum. Cr and Ti were bound to serum proteins within specific molecular weight ranges in both patient groups. Two molecular weight ranges were found to bind Cr (at approximately 70 and approximately 180 kDa) in patients with CoCr alloy prostheses, whereas a single molecular weight range (at approximately 70 kDa) was found to bind Ti in patients with Ti alloy implants. This metal-protein binding was reproduced in vitro by adding CrCl(3) at concentrations of approximately 100 and 1000 ppb Cr, which is orders of magnitude higher than that contained in the serum of patients with CoCr alloy implants ( approximately 3 ppb Cr). This suggests that protein binding is initiated in the periprosthetic space where metal concentrations are typically 2-3 orders of magnitude higher than that observed systemically in the serum. In vitro, high molecular weight proteins including immunoglobulins demonstrated the highest affinity to Cr. Determination of specific protein carriers of metal degradation products is an essential component in the assessment of the long-term biological affects of total joint replacement devices

Wednesday, February 16, 2011

Tissue reaction to metal on metal total hip prostheses. (ion Toxicity 10 of 14)

Clin Orthop Relat Res. 1996 Aug;(329 Suppl):S187-205.
Joint Replacement Institute, Los Angeles, CA, USA.

Abstract

The periprosthetic tissue reaction to polyethylene wear debris in metal on polyethylene total hip replacements is strongly implicated as the cause of osteolysis. This has led to a renewed interest in metal on metal total hip replacements. However, little is known about the role of wear debris in failures of these prostheses. Capsular and interface tissues from 9 long and short term metal on metal total hip replacement retrievals were studied to assess the tissue reaction around these prostheses. As compared with metal on polyethylene cases, the extent of the granulomatous inflammatory reaction and the presence of foreign body type giant cells was much less intense in metal on metal cases, likely because of the lower numbers and overall smaller size of metal wear debris particles. This may lead to a better transport of the particles from the joint tissues and a lower incidence of periprosthetic osteolysis around metal on metal hip replacement.

Metal degradation products: a cause for concern in metal-metal bearings? (Ion toxicity 9 of 14)

Clin Orthop Relat Res. 2003 Dec;(417):139-47.
Department of Orthopedic Surgery, Rush Medical College, 1653 W. Congress Parkway, Chicago, IL 60612, USA. jjacobs@rush.edu

Abstract

In the majority of patients, orthopaedic implants are biocompatible. However, there is an increasing recognition that, in the long-term, permanent orthopaedic implants may be associated with adverse local and remote tissue responses in some individuals. These adverse effects are mediated by the degradation products of implant materials. The recent reintroduction of metal-on-metal bearings for total hip arthroplasty has heightened concerns about the biologic response to metal degradation products in light of the fact that the serum and urine metal concentrations in patients with these implants typically are higher than those seen in patients with conventional metal-on-polyethylene bearings. From previous studies of long-term metal-on-metal McKee-Farrar implants, it seems that these elevated levels may persist for the duration of the implant's lifetime. This is of particular concern in the younger and more active patient in whom life expectancy after implantation may exceed 30 years. The association of metal release from orthopaedic implants with any metabolic, bacteriologic, immunologic, or carcinogenic toxicity currently remains conjectural because cause and effect have not been established in human subjects. However, continued surveillance of patient populations with metal implants, particularly those with metal-metal bearings, is warranted.

Tuesday, February 15, 2011

Serum and urine metal levels in patients with metal-on-metal surface arthroplasty. (Ion toxicity 8 of 14)

J Mater Sci Mater Med. 2002 Dec;13(12):1227-34.
Department of Orthopedic Surgery, Room 756, Cohn Research Building, Rush Presbyterian, St. Luke's Medical Center, 1735 West Harrison St., Chicago, IL 60612-3833, USA. Anastasia_K_Skipor@rush.edu

Abstract

The resurgence of metal-on-metal articulating surfaces for hip arthroplasty has also heightened concerns about the degree and magnitude of metal particle generation and the accompanying increase in circulating metal ion concentrations. In this study, we measured the concentration of chromium in serum and urine and the concentration of cobalt in serum in twenty-five patients with modern metal-on-metal surface arthroplasty of the hip in a prospective manner. The results showed that the mean post-operative chromium in serum levels were 22-fold, 23-fold and 21-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative cobalt in serum levels were 8-fold, 7-fold and 6-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The mean post-operative chromium in urine levels were 9-fold, 10-fold and 14-fold higher at 3, 6 and 12 months post-operative, respectively, than pre-operative levels. The values seen in this study with the current generation of surface arthroplasties are: (a) lower than those seen in an earlier generation of surface arthroplasties; (b) in the same range as those observed in association with metal-on-metal conventional total hip replacements, which typically have smaller head sizes; (c) higher than values observed in patients with conventional metal-on-polyethylene articulating couples.

Cobalt and chromium concentrations in patients with metal-on-metal and other cementless total hip arthroplasty. (Ion Toxicity/7 of 14)

Arch Orthop Trauma Surg. 2002 Jun;122(5):283-7. Epub 2002 Feb 28.
Department of Orthopaedics, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. maeza@med.juntendo.ac.jp

Abstract

We measured the cobalt and chromium concentrations in the serum and urine of 32 patients with current designed metal-on-metal total hip arthroplasty and 43 patients with conventional metal on ultrahigh molecular weight polyethylene (UHMWPE) cementless total hip arthroplasty. The results of our study showed that the serum and urine chromium concentrations increased in 37.5% and 90.6%, respectively, of 32 patients with well-fixed metal articulation (the mean values were 0.09 microg/dl and 2.2 microg/l, respectively) and also increased in 28.6% and 85.7%, respectively, of 7 patients who received metal-on-UHMWPE articulation with loosened acetabular component or stem made of Co/Cr alloy (the mean values were 0.06 microg/dl and 1.6 microg/l, respectively). On the other hand, the serum and urine cobalt concentrations were below the detection limit in all patients.
 

Sunday, February 13, 2011

Cobalt and chromium concentrations in patients with metal-on-metal and other cementless total hip arthroplasty. (Ion Toxicity 6 of 14)

Arch Orthop Trauma Surg. 2002 Jun;122(5):283-7. Epub 2002 Feb 28.
Department of Orthopaedics, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. maeza@med.juntendo.ac.jp

Abstract

We measured the cobalt and chromium concentrations in the serum and urine of 32 patients with current designed metal-on-metal total hip arthroplasty and 43 patients with conventional metal on ultrahigh molecular weight polyethylene (UHMWPE) cementless total hip arthroplasty. The results of our study showed that the serum and urine chromium concentrations increased in 37.5% and 90.6%, respectively, of 32 patients with well-fixed metal articulation (the mean values were 0.09 microg/dl and 2.2 microg/l, respectively) and also increased in 28.6% and 85.7%, respectively, of 7 patients who received metal-on-UHMWPE articulation with loosened acetabular component or stem made of Co/Cr alloy (the mean values were 0.06 microg/dl and 1.6 microg/l, respectively). On the other hand, the serum and urine cobalt concentrations were below the detection limit in all patients.

Cobalt and chromium concentrations in patients with metal on metal total hip replacements. (Ion Toxicity 5 of 14)

Clin Orthop Relat Res. 1996 Aug;(329 Suppl):S256-63.
Department of Orthopedic Surgery, Rush Arthritis and Orthopedics Institute, Chicago, IL, USA.

Abstract

There has been a resurgence of interest in the use of metal on metal bearings in total hip arthroplasty. Although the use of metal on metal bearing couples would eliminate or substantially reduce particulate polyethylene generation (depending on the presence or absence of polyethylene in the implant system), there is concern about the potential for increased particulate and ionic metal generation in comparison with polyethylene on metal bearings. These metallic degradation products may be transported away from the implant site and distributed systemically. Chromium concentrations in the serum and urine and cobalt concentrations in the serum were measured in subjects with cobalt chromium alloy metal on metal total hip replacements and in controls without implants. Eight subjects with long term (> 20 years) McKee-Farrar total hip replacements had 9-fold elevations in serum chromium, 35-fold elevations in urine chromium, and at least 3-fold elevations in serum cobalt concentrations in comparison with controls. Six subjects with short term (< 2 years) metal on metal surface replacement arthroplasties had 3-fold elevations in serum chromium, 4-fold elevations in urine chromium, and 4-fold elevations in serum cobalt concentrations in comparison with subjects with McKee-Farrar implants. Although the toxicologic importance of these trace metal elevations has not been established, serum and urine metal concentrations may be useful markers for the tribologic performance of metal on metal bearings.