Running Head: TOXIC EFFECTS OF METAL ON METAL JOINT REPLACEMENT

Toxic Effects of Metal on Metal Joint Replacement

Caitlyn Hillier Jaclyn Rowley Maranda Hall Hannah Shafer Danyelle McMaster

Youngstown State University

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TOXIC EFFECTS OF METAL ON METAL JOINT REPLACEMENT

Introduction

Joint replacements have become more common in recent years, and people are more

likely to get a joint replacement now than they used to. With the uprising of these surgeries,

more materials have been tested and used. Most metals used have had no reaction within the

patient, with certain exceptions, one of which includes cobalt and chromium metal on metal

replacements. Patients who have cobalt and chromium implants have recently been showing

signs of cobalt toxicity with their metal on metal replacement. Cobalt toxicity arises when the

joint implant rubs together, releasing ions into the bloodstream. Normal serum chromium level in

whole blood concentrations in the absence of any known exposure range from 2.0 μg/100 ml to

3.0 μg/100 mL (Green,2017). A patient with systemic cobalt toxicity symptoms had levels

greater than 100 μg/L (Cheung, 2016). The symptoms of cobalt toxicity come years after

receiving the replacement and can manifest as other diseases and be misdiagnosed. There are

many tests that can be performed, such as blood and urine screenings, as well as neurological

screenings to confirm the diagnosis as cobalt toxicity. Most of the misdiagnoses in patients stem

from their side effects of the metal on metal toxicity. There is a wide range of side effects that

can occur from the cobalt chromium implant, including cardiac issues, neurologic changes,

vision, and auditory changes. There are very few treatment options for cobalt toxicity, options

being therapeutic plasma exchange, and replacement of the metal joint.

Blood and Urine Screenings

With metal on metal joint replacements there are two elements that we are concerned

with causing toxic effects. One being Cobalt, and the other Chromium. Cobalt is a metal element

that is essential in making vitamin B12 in our bodies which is needed for making red blood cells.
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This element is commonly found in beef, tuna, and fortified cereals. The recommended intake is

5-8 mcg a day, although there is not a set safe recommended dietary allowance set (University of

Rochester Medical Center, 2019).

Chromium is a trace mineral that can affect insulin, carbohydrates, fat, and proteins in the

body. Chromium is found in foods such as broccoli, potatoes, and bananas. Recommend intake

for an adult is between 24-50 mcg/day (office of dietary intake, 2018). Normal serum chromium

level in whole blood concentrations in the absence of any known exposure range from 2.0

μg/100 ml to 3.0 μg/100 mL (Green,2017)

When suspected of possible cobalt toxicity a detailed assessment should be done with a

multidisciplinary team. Laboratory investigation should include a “full blood count with

differential, erythrocyte sedimentation rate, C-reactive protein, creatinine, urea and electrolytes,

liver enzymes and liver function test total bilirubin, albumin, international normalized ratio INR

and thyroid stimulating hormone. For the patients with painful MoM prosthesis blood cobalt and

chromium levels should be drawn” (Cheung, 2016).

The mean cobalt levels are known to vary between 0.2 μg/L and 4 μg/L. The MHRA

guidelines suggest that a blood level above 7 μg/L may be indicative of excessive wear in MoM

hip implants (Cheung, 2016). The majority of systemic symptoms had levels greater than 100

μg/L (Cheung, 2016).

There was a study done in the UK that presented ten cases that had MoM hip

replacements done between 2005 and 2009 that required revision surgeries. In this study nine out

of the ten cases had pre-revision blood serum Co and Cr tested. The mean level of chromium was

338 nmol/l with the highest lab value reaching 664 nmol/l. Cobalt the mean was 669.4 nmol/l

and the highest reaching 2470 nmol/l. the highest accepted level for Cobalt being 119, and
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TOXIC EFFECTS OF METAL ON METAL JOINT REPLACEMENT

chromium being 134.5 (Green,2017). Post-surgery 3 of the cases had these levels redrawn, two

of them had nontoxic levels, and the other had sub-toxic levels (Green,2017).

Neurological Screenings Related to Cobalt Toxicity

Multiple neurological complications have been reported in association with increased

cobalt and chromium levels due to metal on metal (MoM) hip replacement surgeries.  These

complications include Parkinsonian like symptoms related to a decrease in extrapyramidal tract

function, depression, polyneuropathy and hearing and vision disturbances.  Many reports of

declined cognition including memory loss, losing objects, concentration impairment (Devlin,

Pomerleau, Brent, Morgan, Diectchman, Swartz, 2013) and the inability to recall words have

even led to a misdiagnosis of early onset dementia in the patients experiencing cobalt toxicity

related to device failure of the prosthesis.  There have been numerous studies conducted to

measure and confirm the neurological effects of the CoCr toxicity and the following section will

discuss these tests and their findings.

Hearing impairment has been cited as the most frequently reported neurological finding

associated with prosthetic hip- associated cobalt toxicity (PHACT).  In a systematic review of

cases it was found that 7 out of 10 patients experienced some form of hearing impairment

(Devlin et al., 2013). Bilateral Sensorineural hearing impairment was indicated as the cause,

which indicates damage to the nerve pathways that lead from the inner ear to the brain. This

finding implies the neurotoxic effects of the increased CoCr levels.   Audiometry testing, which

tests hearing sensitivity involving sound intensity and pitch, was used in patients experiencing

cobalt toxicity both prior to and after revision surgeries. The audiometry testing revealed high-
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TOXIC EFFECTS OF METAL ON METAL JOINT REPLACEMENT

pitched hearing loss, deafness and impairment in patients with PHACT. It was found that post

revision surgery that one patient revealed his hearing was returning (Devlin et al., 2013).    

Cognitive impairment was noted as the second most common effect of cobalt/chromium

toxicity.   In the systematic review done by Devlin (2013) five out of 10 patients were affected.

A study was also conducted by Green, Griffins and Almond in 2017 showed that 7 out of 10

patients were affected by cognitive impairment.  In this study the Mini Mental State Exam or

MMSE was used to measure the cognitive functioning abilities. The MMSE is a bedside exam

that asks a series of questions and is used by many practitioners to measure cognition and to

screen for dementia.  A total score of 30 is possible, with a general score of 28. A score less than

25 indicates cognitive impairment (Green, 2017). The study found that the mean MMSE score

for the patients experiencing prosthetic hip-associated cobalt toxicity (PHACT) was 24.2 which

was found to be extremely high for patients in this age range (Green, 2017).  It was also found in

this study that the patient with the highest CoCr levels also had the lowest MMSE score (Green,

2017).

Depression screening was also performed on 10 patients in the study done by Green

(2017).  The Beck Depression Inventory and criteria from the Diagnostic and Statistical Manual

of Mental Disorders-5 (DSM-5) were used as screening tools for diagnosing depression in this

population.  A significantly depressed mood was found in 9 out of ten patients with a mean score

of 27.6 on the BDI questionnaire (Green, 2017). This score is consistent with moderately severe

depression.  When considering depression levels of patients with PHACT it also must be taken

into consideration that factors such as pain, mobility problems and the fear of being a burden to

loved ones must be accounted for in a holistic view of developing depression.  

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TOXIC EFFECTS OF METAL ON METAL JOINT REPLACEMENT

Paresthesia and polyneuropathy are also common neurological deficits found in PHACT

patients.  Multiple tests are performed to screen for abnormalities involving these conditions.

Electromyography (EMG), which measures electrical activity in response to a nerves stimulation

of a muscle, was found to show a reduction in lower limb nerve amplitude in patients with

PHACT (Devlin, 2013).  A Nerve Conduction Test (NCT) reported similar results, reporting

decreased conduction velocity. Nerve biopsy revealed moderate axonal degeneration with no

inflammatory changes and MRI revealed lesions on the brain that suggested demyelination

(Devlin, 2013).

Visual Disturbances due to PHACT were also among the highest reported neurological

symptoms.  Visually evoked potentials, or a measure of the electrical activity of the brain,

showed irregular cortical visual responses in these patients.  MRI brain scans have also been

used to study the visual effects of CoCr toxicity (Clark et al., 2014). These MRI studies revealed

that patients who had received metal on metal hip replacements tended toward lower gray matter

attenuation in the occipital cortex and basal ganglia had a smaller optic chiasm than the patients

who had received conventional prosthesis (Clark, 2014).  This study also indicated possible cell

loss in the visual system due to circulating metal concentrations (Clark, 2014). In an animal

study rabbits with prolonged CoCr exposure, combined optic and auditory neuropathy was found

(Clark, 2014).

Side Effects

Metal on metal joint replacements made of cobalt and chromium have been found to

increase the serum cobalt and chromium levels in the bloodstream. These elevated and toxic

levels cause multiple side effects including cardiomyopathy, depression, short term memory loss,
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local and systemic neuropathy, visual changes, auditory changes, appetite changes, weight loss,

thyroid disorders, metallic taste to mouth, irritability, and metallosis causing severe pain at the

site of implant (Green, Griffiths, and Almond 2017. p. 1). These symptoms either resolved or

drastically subsided once the revision surgery had taken place. Some of these side effects such as

depression, and irritability can be correlated with the phycology response pertaining to the failure

of the implant (Green, Griffiths, and Almond 2017. p. 4). These side effects are coupled with

anxiety and fear of future surgeries along with guilt from becoming a burden to loved ones.

        The vast majority of side effects revolve around mental status changes. Studies show that

increase chromium and cobalt levels in the bloodstream can cause changes in brain structure and

function. One experiment assessed patients with metal on metal joint replacements mental status

by using the “Mini Mental State Examination.” Patients assessed post metal on metal joint

replacement displayed a MMSE score between 16-26 which was a decreased number from their

pre-replacement MMSE score (Green, Griffiths, and Almond 2017. p. 3). The increased cobalt

and chromium levels are thought to have a decreasing effect on patients mental and cognitive

status. These patients after several years have a hard time with their short-term memory,

decreased long term recall, and depression. This data was not commonly thought to be a side

effect of the joint replacement but rather just a common sign of aging (Green, Griffiths, and

Almond 2017. p. 4). These cognitive changes were not investigated until they found that increase

serum chromium and cobalt had a direct correlation with decreased mental status.

        Depression was also a side effect that was thought to just be due to surgical procedures,

increased aging, and lack of self-care due to decreased mobility with the replacement.

Depression was commonly overlooked as being a side effect of cobalt toxicity (Green, Griffiths,

and Almond 2017. p. 4). These patients going through metal on metal joint replacements went
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TOXIC EFFECTS OF METAL ON METAL JOINT REPLACEMENT

through a lot of pain, in need of a lot of extra help, and not being able to keep up with their

normal day to day schedule which can cause someone to become depressed. During an

experiment of metal on metal joint replacements depression screening tools such as “Beck

Depression Inventory Scores” were used to determine the level of depression that were being

exhibited by the patient. Patients in this experiment exhibited scores ranging from 30 and higher

with a mean score of 36. This shows that most patients with metal on metal replacements show

signs of depression (Green, Griffiths, and Almond 2017. p. 3). Although there is not definitive

evidence showing a correlation between cobalt and chromium levels and depression this is still a

large issue with these joint replacements.

        Other neurological changes resulted in visual and auditory difficulties. Cobalt and

chromium toxicity can cause structural changes in the auditory and visual pathways. The excess

isotopes cause structural neurological damage. This causes direct damage to the nerves that

control the eyes and ears. These side effects were also commonly overlooked due to the

commonality of these side effects with increased age. Many people as they advance in age obtain

poorer vision and hearing, so this was thought to not have any correlation with cobalt and

chromium toxicity (Kavanagh, Kavanagh, and Kraman 2018. p. 92). The same neurological

damage that causes visual and auditory changes causes local and systemic neuropathy. Patients

show signs of decreased sensation, tingling, and burning sensations in the extremities and at the

site due to neuropathy (Green, Griffiths, and Almond 2017. p. 3). At the site of the implant

metallosis is also present that causes even more tissue and nerve damage and a lot of local pain.

        Metallosis is seen in a large number of patients who have undergone metal on metal

replacements (Green, Griffiths, and Almond 2017. p. 2). Metallosis is a rare and potentially fatal

complication occurring after a metal arthroplasty. Metallosis is a deposit and buildup of metal
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TOXIC EFFECTS OF METAL ON METAL JOINT REPLACEMENT

debris in the soft tissues of the body that causes aseptic fibrosis, local necrosis and loosening of

the device (Oliveira and Alves 2014. p. 1). The release of cobalt and chromium ions of the

replacement are caught in the surrounding soft tissues causing death of tissue, destruction of

nerve fibers, and increased pain to the area. This tissue that becomes necrotic must be debrided

and can cause lasting residual effects from decreased nerve function (Oliveira and Alves 2014. p.

3). The finding of metallosis around the replacement helped to prove the presence of cobalt and

chromium toxicity.  

        Another detrimental side effect from metal on metal joint replacements included

cardiomyopathy (Kavanagh, Kavanagh, and Kraman 2018. P. 94). The elevated levels of cobalt

and chromium in the blood cause molecular changes in the heart’s cells. It causes nuclear

changes and deformities such as twisting of the nucleus and poor chromosomal arrangement

(Zadnipryany, Tretiakova, Sataieva, and Zukow 2017. p. 103). This leads to decrease cardiac

function and decrease systemic oxygenation and perfusion to tissues. This side effect was rare

and was not commonly evaluated in the research.

        Many of the other side effects such as metallic taste, loss of weight, and appetite changes

can correlate together. The patients that had poor taste did not want to eat which caused them to

lose weight. The patients that were also depressed due to their replacement exhibit an altered

appetite leading to loss of body weight. The metallic taste is caused by an increase in metallic

ions throughout the body (Oliveira and Alves 2014. p. 3). Poor thyroid function can also affect a

person’s weight. Decreased thyroid function was only mentioned a few times in the experiments

and it was not clear the true causative factors of the decreased function (Kavanagh, Kavanagh,

and Kraman 2018. p. 93) This research is still relatively new and needs further evaluation to see

the true side effects that are caused by chromium and cobalt toxicity.
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Treatments

There are numerous treatments available to deal with the ruthless toxicity that Cobalt

poisoning causes innocent patients from joint transplants. Cobalt binds to albumin; once the

circulation of this metal begins to continually flow throughout the human body, it has a tendency

to be disguised as other disorders and hide behind its real cause for physical changes. The

amount of time that this disorder begins to be manifested is specific to the patient and varies

from person to person. After reading an interesting case study by Hemapheresis, I was able to

draw a significant number of conclusions from the article. The reading discusses an older woman

with osteoarthritis from 2004 who received a left hip arthroplasty using a ceramic on ceramic

implant. In May of 2015, the woman experienced a wearing down of the ceramic lining causing

“sand like” debris around the surrounding tissue. After fragments of ceramic debris were

discovered throughout the tissue, irrigation and removal were performed by medical professions.

A month later, a new surgery was performed consisting of metal on metal cobalt implantation.

Shortly after the operation, the patient did not experience much trouble mentally, or physically;

there was also little impact on mobility, sleep, or her mental status. Within time, the normality of

the patient’s livelihood took a detrimental turn as the wrath of cobalt toxicity began to peak.

Insomnia and polydipsia were two unbearable side effects experienced by this patient that began

to negatively impact her life. After a thorough physical examination, a heart rate of 141 beats per

minute, limited movement of her left hip, and even unexplained weight loss. Blood work was

performed revealing elevated levels of hemoglobin, hematocrit, and glucose; antidepressants and

sleeping aid pills were conservatively prescribed before the disorder was acknowledged or

discovered. The element of cobalt coincidentally binds to a protein known as albumin which

could explain a profuse elevation seen in blood values. The symptoms continued to worsen as
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time progressed consisting of hearing and vision loss, cardiac complications, easy dislocation,

nausea, vomiting, paresthesia, gastritis, and even driving inability. As these side effects began to

summate, the health team began to arrive with a cumulated diagnosis: Cobalt Toxicity. Blood

levels were drawn revealing a level of 2,148 ug/L of cobalt within the bloodstream. At this point

in time, a therapeutic method of plasma exchange and hemodialysis was performed in order to

reduce the level of cobalt resulting in a rebound of elevation of the element in only eight hours

due to the implant remaining in the hip. The health team continued to attempt noninvasive

techniques without the realization that one method was needed to cease the madness of this

disorder: transplant removal. (Grant, Karp, Palladino, Le, Hall, and Herman 2016)

A following study by BMC Psychiatry discussed the toxic effects of MoM implants in ten

cases. After countless attempts to cease the brutal effects that Cobalt transplantation has on one’s

body, medical professions arrived the only optimal treatment for health restore: removal. “Other

than revision surgery there is no effective adsorption or chelation therapy for chromium and

cobalt, and if such therapies could be safely developed, it may avoid the need for further

surgery”(Green, Griffiths, and Almond, 2017 p. 4). Regardless of multiple measures, true

removal of the transplant is the only alternative to truly attempt to eradicate the deadly causes

Cobalt promotes.

Conclusion