The Breakdown of Metal Toxicity

On June 28th, 2012, During the Second Day of the FDA’s Orthopedic Surgery and Rehabilitations Device Panel, the Administration presented on Local and Systemic Complications for different types of orthopedic devices.

Dr. Katherine S. Squibb, PhD of the University Of Maryland School Of Medicine presented the panel with an Overview of the Toxicity of cobalt and chromium metals found in metal on metal hip implants.

There are four major determinants of metal toxicity: Chemistry of the metal, the exposure dose, route of exposure, and the duration of exposure.

Chemistry: The metal’s chemistry is affected by the solubility, the oxidation state, and the preferred ions or molecules bound to the central metal atom.

Exposure Dose: The severity of the dose is determined through absorption, tissue distribution, metabolism, and excretion.

Exposure Route: There are three main routes of exposure to metal toxicity: Inhalation, ingestion and dermal. In the case of hip implants the metal travels through the blood. The release route can either be systemic, traveling through the blood from one part of the body to another or a more localized release affecting the tissue surrounding the metal implant.

Exposure Duration: The duration of exposure can play a huge part in the severity of toxicity. Chronic exposure is more severe than a small amount of acute exposure. The rate in which the metal is being released and exposed to the blood stream is also vital to the level of toxicity.

Toxicity Determinants of Metal on Metal Hip Components
If you look at the chemistry of chromium, you find the two most common oxidation sates are chromic (Cr+3) and chromate (Cr+6). Chromic is the more naturally abundant form in the environment. A form of this metal is vital for metabolism of glucose. A CR+3 Deficiency can lead to impaired glucose intolerance, peripheral neuropathy and elevated serum insulin, cholesterol and triglycerides. Cr+3 is less toxic than Cr+6. Absorption of chromate is much higher in the GI track than chromic, which can make the kidneys a primary target for metal toxicity.

The other major metal used in MoM hip implants is Cobalt. This relatively rare metal has chemical properties similar to that of iron and nickel. The two major oxidation states for cobalt are Co+2 and Co+3. The essential trace element in cobalt is cobalamin, a component of Vitamin B12 that is required for the production of red blood cells. The change in the valence state from Co +2 to +3 can be an important mechanism of toxicity as it involves the transfer of electrons and the formation of free radicals.

Chronic doses of both chromium and cobalt would be more harmful than a limited one-time exposure. Chronic doses of chromium exposure can have different impacts depending on the route. Chronic dermal exposure can lead to an allergic sensitivity which will likely cause rashes or asthma. Chronic inhalation of chromium can lead to lung cancer. This is more likely to happen to workers in a manufacturing plant who are inhaling chromium particles on a daily basis.

Studies of the accumulation of cobalt in the blood cells caused by chronic exposure primarily affected the blood, liver and kidneys in lab animals. In humans, cobalt has caused thyroid toxicity in some alcoholics consuming beer with a cobalt foam stabilizer. As with chromium factory workers periodically exposure to cobalt suffered side effects from toxicity, specificity hearing loss, atrophy of the option nerve, allergic sensitivity and more recently ischemic heart disease for those exposed to hard metal dusts. There are no studies at the moment linking cobalt exposure to cancer in humans, but animal studies have demonstrated lung tumors present in rodents that inhaled cobalt sulfate. Local sarcomas develop from implanted cobalt compounds.

High does of both Cobalt and Chromium can cause rental toxicity and lead to a decreased function of the kidneys. Metals attached to proteins with a low molecule weight and amino acids pass through the network of capillaries that begin the nephron blood filter for the kidneys and are reabsorbed by cells in the duct system
Cytotoxicity of these sells can lead to shedding of cells from the tubule basement membrane and ultimately lead to decreased flow through the system.

Because allergic sensitivity and renal complications are two of the most common side effects from cobalt and chromium toxicity, patients who suffer from lymphocyte response assays, diabetes and currently take drugs with a risk of rental toxicity may not be good candidates for metal on metal hip implants. Patients with a history of cardiomyopathy or thyroid problems, or individuals who may have had occupational or other prior exposure to metals may want to look at other options before deciding to get a metal on metal orthopedic device.

Metal on Metal hip replacements have become the prosthetic of choice for orthopedic surgeons over the last 10 years. Most believed them to be sturdier than traditional ceramic implants and expected them to have a longer life. Unfortunately, metal on metal hip implants were recently found to have a higher than expected early failure rate, most of these failures caused by metal toxicity. During the Medical Device Panel, Doctor Squibb provided an excellent presentation on the dangerous effects the key metals are known to have on human beings. Prolonged exposure of chromium and cobalt have been harmful through various exposure routes. Perhaps the metals chemistry could have something to do with the failure of the device?

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