Page 1, 2
The most fundamental rule of toxicology is to eliminate the exposure(s). Dreadful revision surgery with non-M/M prosthetic materials goes a long way in that regard. However, patients that do not have revisions have perpetual exposure to the offending metals. It is generally recommended that chelation therapy should be reserved for patients who cannot undergo revision. A strong case could be made for consideration of chelation after revision. In one reported case the symptoms of severe arthroprosthetic cobaltism, except deafness, were gradually resolved with DMPS-enhanced decorporation of Co after revision.23 Chelation with EDTA has also been suggested as a treatment option post-revision.25 In animal models of cobaltism, EDTA has been shown to be the most effective chelator.26,27
The big question is what can be done on an ongoing basis for asymptomatic patients who still bear functional M/M THA prosthetics? Aminothiols such as N-acetyl-cysteine (N-AC) and glutathione (GSH) have been long known to increase Co excretion and decrease tissue Co levels following acute Co intoxication in animal models.26,27 More recently, various aminothiols administered in different forms orally or intravenously were compared with respect to enhancing 60Co excretion in a rat model.28 After five daily doses, intravenous and oral liposomal GSH were most effective at enhancing 60Co excretion; 64% and 47%, respectively. Oral cysteine was slightly less effective in lowering tissue 60Co than IV cysteine. Poorly bioavailable powdered oral GSH was without effect. In patients, the beneficial effects of N-AC to enhance Co excretion have been reported as well.22,27 Of particular interest was the efficacy of very high-dose oral N-AC (300 mg/kg) for ten days to markedly lower blood Co and Cr (up to 87%), and enhance urinary Co excretion.27 In one case the effects of the N-AC to lower blood Co persisted for about six months. That data from the patients who did not undergo revision surgery are very encouraging, but it would seem to make more sense to use an aminothiol at a reasonable dose habitually.
Chelation therapy should be given serious consideration for managing the perpetual release of Co and Cr and associated pro-oxidative effects after M/M THA. Selection of a chelating agent, timing of administration, and clinical efficiency are subjects of debate.29,30 Currently there are no established indications for chelation therapy for asymptomatic M/M THA patients. There are case reports regarding chelation with Ca-Na2-EDTA or DMPS for asymptomatic M/M THA patients, but that application has not been appropriately evaluated. EDTA has good affinities for Co, Cr,3 V, and Ti, in vitro,31 and it has been used to treat severe acute experimental cobaltism (animal models).32 Intravenous EDTA also enhanced free Cr3 excretion in human subjects, and significantly decreased oxidative stress and damage to DNA.33 Without revision that uses more compatible prosthetic materials, the source of exposure is still present, and metal levels would no doubt rebound over time after chelation.
Clinical research regarding chelation after M/M THA is long overdue. Intravenous EDTA appears to be the agent of choice, but issues regarding the frequency and number of rounds of periodic chelation are open for discussion. There is no evidence that chelation will adversely affect the integrity of the prostheses or increase the rate of release of the metals from the devices. It is proposed that a protocol incorporating dietary/supplemental antioxidants, and metal conjugating agents (e.g. liposomal GSH, N-AC), and intermittent chelation may greatly ameliorate the potential, local and systemic toxic effects associated with the life-long release of metals in patients with M/M THA prosthetic devices. What say you?
Page 1, 2
David Quig, PhD, received his BS and MS degrees in human nutrition from Virginia Tech and a PhD in nutritional biochemistry from the University of Illinois. After a five-year stint as a research associate studying lipid biochemistry and cardiovascular disease at Cornell University, he worked as a senior cardiovascular pharmacologist for seven years with a major pharmaceutical company. For the past 22 years, David has served as the Vice President of Scientific Support for Doctor's Data, Inc. He has focused on toxic metals, methylation and amino acid metabolism, the clinical application of the biochemistry of endogenous detoxification, and the influence of the gastrointestinal metabolome on health and sustained adverse conditions. David regularly speaks at national and international medical conferences and has facilitated and co-authored an array of studies, spanning exposure and retention of environmental toxicants, nutritional status, and gastrointestinal dysbiosis.