Calcium, Calcium in biology, Cobalt chrome, Cobalt poisoning, DePuy, DNA repair, Erythropoietin, Hip Replacement, Hypoxia (medical), Occupational exposure limit
Cobalt metabolism and toxicology-A brief update.
– My DePuy Hip Recall
by Connie on Aug 13, 2012 7:13 AM
Sci Total Environ. 2012 Aug 15;432:210-5. Epub 2012 Jun 23.
Simonsen LO, Harbak H, Bennekou P.
Cobalt metabolism and toxicology are summarized. The biological functions of cobalt are updated in the light of recent understanding of cobalt interference with the sensing in almost all animal cells of oxygen deficiency (hypoxia). Cobalt (Co(2+)) stabilizes the transcriptional activator hypoxia-inducible factor (HIF) and thus mimics hypoxia and stimulates erythropoietin (Epo) production, but probably also by the same mechanism induces a coordinated up-regulation of a number of adaptive responses to hypoxia, many with potential carcinogenic effects.
This means on the other hand that cobalt (Co(2+)) also may have beneficial effects under conditions of tissue hypoxia, and possibly can represent an alternative to hypoxic preconditioning. Cobalt is acutely toxic in larger doses, and in mammalian in vitro test systems cobalt ions and cobalt metal are cytotoxic and induce apoptosis and at higher concentrations necrosis with inflammatory response.
Cobalt metal and salts are also genotoxic, mainly caused by oxidative DNA damage by reactive oxygen species, perhaps combined with inhibition of DNA repair. Of note, the evidence for carcinogenicity of cobalt metal and cobalt sulfate is considered sufficient in experimental animals, but is as yet considered inadequate in humans. Interestingly, some of the toxic effects of cobalt (Co(2+)) have recently been proposed to be due to putative inhibition of Ca(2+) entry and Ca(2+)-signaling and competition with Ca(2+) for intracellular Ca(2+)-binding proteins.
The tissue partitioning of cobalt (Co(2+)) and its time-dependence after administration of a single dose have been studied in man, but mainly in laboratory animals.
Cobalt is accumulated primarily in liver, kidney, pancreas, and heart, with the relative content in skeleton and skeletal muscle increasing with time after cobalt administration.
In man the renal excretion is initially rapid but decreasing over the first days, followed by a second, slow phase lasting several weeks, and with a significant long-term retention in tissues for several years. In serum cobalt (Co(2+)) binds to albumin, and the concentration of free, ionized Co(2+) is estimated at 5-12% of the total cobalt concentration.
In human red cells the membrane transport pathway for cobalt (Co(2+)) uptake appears to be shared with calcium (Ca(2+)), but with the uptake being essentially irreversible as cobalt is effectively bound in the cytosol and is not itself extruded by the Ca-pump.
It is tempting to speculate that this could perhaps also be the case in other animal cells. If this were actually the case, the tissue partitioning and biokinetics of cobalt in cells and tissues would be closely related to the uptake of calcium, with cobalt partitioning primarily into tissues with a high calcium turn-over, and with cobalt accumulation and retention in tissues with a slow turn-over of the cells.
The occupational cobalt exposure, e.g. in cobalt processing plants and hard-metal industry is well known and has probably been somewhat reduced in more recent years due to improved work place hygiene.
Of note, however, adverse reactions to heart and lung have recently been demonstrated following cobalt exposure near or slightly under the current occupational exposure limit. Over the last decades the use of cobalt-chromium hard-metal alloys in orthopedic joint replacements, in particular in metal-on-metal bearings in hip joint arthroplasty, has created an entirely new source of internal cobalt exposure.
Corrosion and wear produce soluble metal ions and metal debris in the form of huge numbers of wear particles in nanometric size, with systemic dissemination through lymph and systemic vascular system. This may cause adverse local reactions in peri-prosthetic soft-tissues, and in addition systemic toxicity.
Of note, the metal nanoparticles have been demonstrated to be clearly more toxic than larger, micrometer-sized particles, and this has made the concept of nanotoxicology a crucial, new discipline.
As another new potential source of cobalt exposure, suspicion has been raised that cobalt salts may be misused by athletes as an attractive alternative to Epo doping for enhancing aerobic performance. The cobalt toxicity in vitro seems to reside mainly with ionized cobalt.
It is tempting to speculate that ionized cobalt is also the primary toxic form for systemic toxicity in vivo.
Under this assumption, the relevant parameter for risk assessment would be the time-averaged value for systemic cobalt ion exposure that from a theoretical point of view might be obtained by measuring the cobalt content in red cells, since their cobalt uptake reflects uptake only of free ionized cobalt (Co(2+)), and since the uptake during their 120days life span is practically irreversible.
This clearly calls for future clinical studies in exposed individuals with a systematic comparison of concurrent measurements of cobalt concentration in red cells and in serum.
- Cobalt metabolism and toxicology-A brief update (earlsview.com)
- MoMs Hips a Grinding Dilemma for Hospitals, Doctors, FDA (earlsview.com)
- Dr Stephen (Steve) Tower to Join the Earl’sview site – to answer patient questions (earlsview.com)
- Kershaw, Cutter & Ratinoff Launches New Website with Information on Cobaltism, Metallosis, Cobalt & Chromium Toxicity (prweb.com)
- Long-Term Health Risks Associated with Genotoxic Nanoparticles Released by Failing Metal-on-Metal Hip Implants (earlsview.com)
- UK – S&N BHR HELL – Trevor (General Practitioner) Gets Rude Response from Smith & Nephew (earlsview.com)
- ‘Toxic’ hip replacement fears – Health – Belfast Newsletter (earlsview.com)
- ‘Toxic’ hip replacement fears – UK Health News – Isle of Man Today (earlsview.com)
- Stryker Lawsuit – Hip Replacement – Rejuvenate, AGB & Trident (earlsview.com)
- Look of the Day: Cobalt Cutie (fabsugar.com)
Excellent article providing valuable information, Dr. Stevens. This has been printed out and will be taken to a new doctor I am seeing Re: my MoM hip for the first time tomorrow. The contents help explain the deleterious symptoms that have arisen in many of us in the BHR ‘boat’, i.e., you, Howard, Lee, myself, et al. I have experienced significant arthritic degeneration in all of my heavily utilized major joints, and my left hip (opposite my MoM implant) now shows moderate degeneration and has begun to hurt in the past six months. There was no degeneration pre-MoM replacement. I have the same situation now in my right shoulder, extremely painful such that when I sleep (if I can that night) my sleep is now often interrupted by severe pain in that shoulder. (My arms are generally placed under my head and I fall asleep on my back, and a few months ago I awakened to excruciating pain, such that I had to use my left arm to raise my right one, the pain great enough to inhibit the right arms movement on its own.
I have had many other bizarre and unexplained symptoms this past eight or nine months that I had not understood, and my gastrointestinal tract seems significantly distressed, with constipation, cramping, and uncontrollable diarrhea (often mixed with some bright bloody content and a strange, mucus-like gel). I cannot ‘hold’ my sphincter tightly enough to prevent leakage, and have also had to insert a ‘ball’ of tissue soaked witch hazel to avoid soiling myself and easing the very serious pain ten bowel movements per day cause. Last week four pairs of underwear were changed in one day, with the first ‘discharge’ occurring as I slept (I have never had anything like that occur in my life. It is embarrassing to admit but on topic.
This is what lack of in serious and independently monitored in vivo testing has wrought, where we MoM recipients have unwittingly been the test subjects.
Thanks for what you do, Earl, and this will help the rehab specialist in his examination of my various maladies, which evidently have or are being caused by metal toxicity.
Yes – I think we will all take our MoM experience to the grave.
I get sick of unexplained problems too. Like my trip to hospital with extreme pain 4 weeks ago.
But every day above ground is a bonus, I think!
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