Metal ion release after total hip replacement

Metal ion release afbr total hip replacement H.S. Dobbs Department of Biomedical Engineering, The Institute Brockley Hill, Stanmore. Middlesex, HA74LP. UK

of Orthopaedics,

Royal National

Orthopaedic

Hospital,

and M.J. Minski University (Received

of London Reactor Centre, Silwood Park, Ascot, Berks, SL5 7PY, 13 June 1980; revised 25 June 19801

The concentration measured

of cobalt

using neutron

bilateral

cobalt

(Co), chromium

activation

chromium

molybdenum

remained

lung, kidney,

for 5.5 years. Although

liver and spleen were up to fifty

to the metal-on-plastic

the implant.

in the urine, whereas

(Ni),

iron (Fe) and zinc (Zn) was at necropsy.

painful,

the

of Co and Cr in the

Man’ values. High values occurred laden with

had

had been in place

side had become

that the concentrations

joint was heavily

The patient

one, a metal-on-metal

the metal-on-metal

indicated

times ‘Standard

to the metal-on-metal

joint was relatively

Co predominated

(MO), nickel

from an 81 year old female

total hip replacements:

active until she died. The measurements

and in the hair. The tissue adjacent adjacent

molybdenum

(Co-Cr-Mo)

for 14 years, the other a metal.on-plastic patient

(Cr),

analysis in tissue taken

UK

also in the urine

metal wear debris, whereas

uncontaminated.

The concentration

varied with distance

Cr predominated

near the implants.

The existence

that

from

of such high

levels, especially in the organs, is a possible cause for concern,

During

the past thirty

years Co-Cr-Mo

and stainless steel have

been used in the body as orthopaedic able success. There has, however, which

has caused concern.

cases of dermatitislm5 related tumours become

procedure’0-‘6. corrosion

case

In addition

implants,

failure

it is known

of the

quantity

to contain as shown

of only three reports

in the

the systemic effects of metal ions 20 released from orthopaedic implants in man. The first

compared

concerning

levels of Co and Cr in the blood,

hair before and after total hip replacement. increased

levels occurred

(Co-Cr-Mo joints

for metal-on-metal

on CO-O-MO),

(CO-O-MO Co-Cr-Mo

The third2’

metal-on-metal

reported

hair following

Significantly joints

The second”

raised levels of Co in the liver, caecum, following

benefits which

of total

of released of implantation

what levels can be expected

Further

information

would

it is not known

in the

be of obvious

whether

significant,

the levels

nor what period

hip replacement

outweigh

The present report

of

prostheses,

the risk of

is a study of the levels

occur after long term implantation

Co-Cr-Mo

studies have

the quantity

can be regarded as safe in the sense that the

of bilateral

and provides data on the release of

Co, Cr. MO, Ni, Fe and Zn both locally

kidney

CLINICAL

and systemically.

DETAILS

In February

reported

and brain

total hip replacement.

no increase in the level of Cr in the

stainless steel metal-on-plastic

whether

occur are clinically

implantation

and

urine and

but not for metal-on-plastic

on polyethylene).

both the

solutionsz7,**,

of these ions on tissue cultures2g*30.

value. For example,

adverse effects.

We are aware, however,

ions into physiological

In spite of these reports only preliminary

which

in Table 1. literature

effects22-26.

tests have demonstrated

been made to determine

long term31*32.

associated with adverse

in considerable

in the organs,

or other

metal ions in the tissues increases with period

that both wedr and

and was found

associated tumours

and if so to determine

and the tissue itself has been

by various techniques

as well as concentrations

laboratory

release of metal

have

studies of tissue

are sometimes

metal ions, sometimes

patients

with

the adverse effect

metals and it is argued

leads to the eventual

From histological

products

sometimes

there have been

Certain

metal implants

remark-

and a very few cases of possibly

tissue reactions’7-1g, analysed

For example,

to the constituent

that this sensitivity

with

been the occasional

or other effects6-g.

sensitized

surrounding

implants

1965,

the patient

had a total hip replacement

in her right side. She was 67 years old and had bilateral osteoarthritis. The component was a Co-Cr-Mo” Stanmore metal-on-metal

total hip replacement

(Mk 1). It consisted

of a femoral

type head of 41.5 mm diameter,

total hip

of very early design

component

with

Either

and an acetabular

replacement. In animal reported,

experiments

namely,

0142-9612~801040193-06

similar findings have been

local contamination

in the vicinity

of

502.00

IPC Eus~ness

Press

3

1980

‘The chemcal Standard (B.S.

composition 3531, 1962

complied and 1968).

wth

B~omatenals

the

1980.

relevant

British

Voi 1 October

193

Metal

ion release:

Table 1

H.S. Dobbs and M.J.

Metal levels in adjacent

Minski

tissue in man following Implant

Williams & Meachim” Evans et al to

co-c+

N.A.A. N.A.A.

26

Steela Co-C@

N.A.A. A.A.S.

22

Postel & Langlais40

Co-C+ Co-C+

S.E.S. A.A.S.1N.A.A.

Michel & Zil kens@

Steela

N.A.A.

Tia

Lux 84 Zeisler41 Jones et al 11 Smethurst & Waterhouse3

b

N.A.A.

Method

(ppm)

Reference

a

type

implantation

Reference Coleman, Herrington Scales20

total hip

Location

Co

Cr

Cobalt chrome metal-on-metal

Blood Urine Hair

0.006 0.024 0.42

0.004 0.006

Cobalt chrome metal-on-metal

Liver Caecum Brain Kidney

3 0.5 1 1

Steel metal-on-plastic

Hair

implant

type

and

Jonesetallt

Owen, Meachim and Williams21

(dry) (dry) (dry) (dry)

*The chemical composition complied with the relevant Standard (B.S. 3531,1962 and 19681.

Biomaterials

7980,

Vol 1 October

Fe

Ti

Basis

2000

Dry Wet’ Wet+ Dry Wet ?

10

50

580

l

1300 1500

4 6000

376

103

l

2067

4010

= Atomic absorption spectroscopy = Spark emission spectroscopy = Not stated, but determined by subsequent

Dry

inquiry

impinged on the neck of the femoral components. There was no thickening of the fibrous capsule and no free fluid within the joint. Next the abdomen and thorax were opened and the spleen, the right kidney, a lobe of lung and a piece of liver were removed. All the removed material was stored in separate containers in formal saline. A urine sample was taken from the bladder and a hair sample from the head.

METHOD <2

component with cup and separate liner. The stem was attached with acrylic bone cement, and the cup was pinned into the ilium, ischium and pubis. At operation both components were very firmly attached. Post-operatively the patient made a normal recovery. She had good range of movement and walked with crutches. After a few years there was a suggestion of looseness, accompanied by noise and pain. At this time she was still satisfied with the result, but later (in 1977) she was not. In August 1973, when she was 75 years old, she had a total hip replacement on her left side. This was a Stanmore metal-on-plastic total hip replacement of recent design (Mk 7) and consisted of a Co-Cr-Mo” stem, a 25 mm head, and a polyethylene (RCH 1000) cup. Both components were attached with acrylic bone cement. A year later she was satisfied with both her hips and walked over a mile a day using elbow crutches. She did her own gardening and housework. In January 1979, she died of a heart attack at which time the former joint had been in place for 14 years and the latter for five and a half years. At necropsy both femora and acetabula were excised. On opening the metal-on-metal joint it could be seen that the head and cup were highly polished where the surface was worn, and the surrounding joint capsule and tissue were pale green (Figure 7).There was an extensive granuloma, also discoloured, extending along the psoas tendon. The cup was loose and one of the pins had pierced the acetabulum, and had protruded into the abdominal cavity. Some dark fluid was aspirated from the joint. On opening the metalon-plastic joint there was nothing abnormal to be seen. Both components were firmly fixed and there was no evidence of metallic wear debris or of discolouration, although the rim of the cup had worn slightly where it had

194

85 130 6000

Ni

103

l

levels of metal in man following

MO

Cr

A.A.S. S.E.S.

= Fixation device = Metal-on-metal total hip replacement = Neutron activation analysis

Table 2 Systemic replacement lppm)

co

Four days after necropsy the material was removed from the formal saline. Samples of tissue were prepared using a titanium knife. Samples of bone and acrylic bone cement were prepared using a hand saw and were then trimmed with the knife to remove possible contamination from the saw. All the samples were weighed before and after drying; the wet weight was approx. 1 g in each case. They were dried either by air-drying in an incubator at 37°C or by freezedrying. Samples were also prepared from 1 ml of the joint fluid, from 10 ml of the urine and from 10ml of the formal saline. A sample of hair, approx. 0.5 g and untreated after removal from the scalp was prepared. Metal samples were also taken from each of the prostheses. All the samples were stored in small plastic containers and were irradiated in the University of London Consort Reactor for 100 hours at a neutron flux of - 1 x 1 012n cmW2: together with standards. After a decay period of five days th samples were transferred to clean containers and analysed by gamma spectrometry using a Ge (Li) semi-conductor detector, resolution 2.2 keV at 1322 keV, connected to a 4000 channel analyser. Counting times were between 2-3 hours per sample. Peak analysis was by the Covell33 method. The detection limit in ppm for irradiation of a sample weighing one gramme was as follows: 0.003 Co, 0.03 Cr, 0.04 MO, 0.4 Ni, 5 Fe and 0.1 Zn.

British Figure

1

The metal-on-metal

joint at necropsy showing granuloma

Metal

ion release:

H.S. Dobbs and M.J.

Minski

RESULTS Tab/e 3 gives the chemical

composition

It can be seen that the alloy contains 2

of the components. Co and Cr in the ratio

: 1, some MO and a little Ni. Fe and Zn were not detectable. The following

analysis was obtained

saline sample before storage (ppm): <0.03

MO, 0.003

was concluded formal

Co, 0.006

it

that the tissue samples could be stored in

saline without

significant

contamination.

tables the concentrations

ppm or more precisely of the wet weight,

are given in

in c(g/g for the tissue and in pg/ml

For the tissues the concentrations

wet weight

Cr.

Ni, 0.09 Fe, and 0.07 Zn from which

In the following the fluids.

for the formal

0.001

but the factor

to ppm dry weight

for

are as a function

needed to convert

from

ppm

is also given, this factor

being the ratio of the wet weight

to the dry weight.

Tab/es 4 and 5 give the values of Co, Cr, MO, Ni, Fe and Zn (also the Co:Cr the metal-on-metal

ratio)

in the immediate

and metal-on-plastic

Values are given for the following: and granuloma neck of femur

(all adjacent

joint

fluid,

joint capsule,

tissue from the

from the mid-femur

For the metal-on-metal

Figure

results can be noted: side, very high levels occurred

for Co and Cr. and to a lesser extent

2 is a photomicrograph

section of the granuloma magnification

of 560x.

macrophages

inundated

being one micron

(15 cm away) and bone cement (adjacent to the rim of the plastic cup). The following

with

Co-Cr-Mo

implants

for MO and Ni,

as a function

side, relatively

low levels

released by corrosion

rather than wear.

with wear debris, each particle

the variation

of distance

the location

suggesting that the levels

separately

For both sides Cr was more plentiful

adjacent

than Co in the

of the joint.

distance Approximate

chemical

composition

Sample

Side

Co

Cr

Femoral component

metal-on-metal

60.9

29.5

from the implant

Ni

Co:Cr

on-plastic

1.0

2.1:1

Cup Femoral component

Table 4

metal~n-metal

metal-on-plastic

Metal concentration

60.0

55.5

29.1

32.6

9.0

1.8

10.1

on the metal-onmetal

1.8

2.1:l

1.7:1

adjacent

bone value, which on-metal

roughly

than for cortical

of Cr,

increasing

constant

levels

values were

bone. On the metalfor bone and acrylic

to the cup as shown in Table 5, The

is considerably

side, is plotted

lower than for the metal-

in the figure for comparison.

Table 6 gives the concentration Fe and Zn (also the Co : Cr ratio) organs, hair and urine.

with

the initial

side, values were obtained

bone cement 8.6

reaching

for Co and Cr. For both elements higher for cancellous

MO

4, each data

very high levels, especially

but these fell off rapidly

1%)

of components

to

to the centre of each piece. Again,

to the implant

were recorded,

Table 3

bone,

and the groove corresponds

and the results are shown in Figure

point corresponding

vicinity

was about

of the rim of the cup. Each piece was analysed

decreased with distance from the joint. immediate

which

3. The lower pieces are compact

immediate

position,

a radial section

to the cup on the metal-

The section,

the upper ones cancellous,

at the mid-femur

ion concentration

was cut into six pieces, each about 8 mm wide,

as shown in Figure

of the joint were higher than those

of granuloma.

in metal

from the implant

For both sides the levels of Co, Cr; MO and Ni in the vicinity

who observed both the fine

adjacent

side was taken.

5 mm thick,

are in

on the tissue response to

by Winterf8

the acetabulum

on-metal

side at a

The tissue consists largely of

previous work

To estimate through

suggesting that the metal may have been

of a stained histological

on the metal-on-metal

size of the wear debris and the incidence

laden with wear debris. For the metal-on-plastic

wear debris;

or less in size. These observations

agreement

suggesting that the tissue and joint fluid were heavily

occurred

showing particulate

of

joints respectively.

to the joint),

(5 cm from joint),

vicinity

Figure 2 Section of granuloma haematoxylin and eosin Ix 560J

of Co, Cr. MO, Ni,

in the samples of the

For comparison

Tab/e 7 gives the

side (ppm wet weight)

Sample

co

Cr

MO

Ni

Fe

Zn

Factor

Co:Cr

Joint Fluid Joint Capsule Granuloma Tissue (mid femur)

12.94 62.6 193.1 6.90

63.32 327.2 322.8 5.52

3.97 6.6 < 0.03 0.74

1 .29 2.78 3.18 0.40

11.59 158.3 320.9 32.5

4.08 16.8 91.8 8.7

3.1 5.0 2.3

0.1 : 1 0.2 : 1 0.6 : 1 1.3 : 1

Table 5

Metal concentration

on the metal+nqlastic

side (ppm wet weight)

: Cr

Sample

co

Cr

MO

Ni

Fe

Zn

Factor

Co

Joint Capsule Tissue (neck) Tissue (mid femur) Bone Bone cement

0.61 1.34 0.21 0.56 0.12

0.90 1 .04 0.34 8.32 < 0.01

0.44 0.59 0.14 < 0.03 < 0.03

1.83 0.42 0.27 < 0.4 <0.4

222.9 115.0 23.2 159.2 6.7

7.4 5.5 7.9 61.6 3.9

3.2 3.6 2.7 1 .4 1 .l

0.7 : 1 0.6 : 1 1.3 : 1 0.1 : 1 >12:1

Nomaterials

1980.

Vol I October

195

Metal

ion release:

Table 6

H.S. Dobbs and M.J.

Metal concentration

Minski

in the organs, hair and urine &pm

wet weight)

Sample

co

Cr

MO

Ni

Fe

Zn

Factor

Co : Cr

Lung Kidney Liver Spleen Hair Urine

0.24 0.31 0.47 0.23 0.68 0.07

0.18 0.39 0.61 0.56 1.39 0.04

0.12 0.16 0.68 0.23 < 0.03 < 0.03

0.39 0.15 0.64 < 0.4 1.46 .O.Ol

181.5

6.30 15.36 35.90 12.80 193.5 0.39

6.3 3.8 4.0 4.3 -

1.3:l 0.8: 1 0.8 : 1 0.4 : 1 0.5: 1 1.75:1

Table 7 Standard

Metal concentration in normal human #an’ va/ues34 @pm wet weighty

tissue and urine,

Ni

Tissue

Co

Cr

Mo

Lung

0.02

0.09

0.03

0.05

360.0

11.0

Kidney

0.013

0.01

0.035

0.05

74.2

48.4

0.06

0.009 0.007 0.25 0.006

177.8

47.2

272.2

17.8

Liver Spleen Hair (female) Urine

0.035 1 .O 0.02

1 .o

<0.06

0.055

0.06

0.01

0.5 0.006

Fe

Zn

2.0 0.07

17.0 0.13

mean value of the concentration in normal tissue of these metals, atl of which are present to some extent. The values given are the ‘Standard Man’ values34 obtained from various sources35-38. The following results can be noted: 7. For the organs the levels were considerably raised for Co and Cr (up to fifty times normal values), slightly raised for Ni and MO, unchanged for Fe and decreased for Zn. 2. For the hair the level of Cr was considerably raised; the level of Co, namely 0.69 ppm, was a factor of ten greater than the value obtained ten years earlier for the same patient, namely 0.06 ppm.” 3. For the urine the values of Co and Cr were raised as compared with normal values. 4. Cr was more plentiful in the organs and in the hair, but Co was more plentiful in the urine and lungs.

Comparison

with previously

796

Biomaterials

1980,

488.4 321 .J 34.9 1 .os

greater than the value of 0.96 ppm obtained for females by Schroeder and Nason43. Our results for the location dependence of the Co: Cr ratio suggeststhat Co is more mobile than Cr, which is consistent with previous findings20,31,*. Our results, however, demonstrate for the first time that Co and Cr are both absorbed by the tissue at a considerable distance from the implant. Such mobility had previously been ascribed to Co, but not to Cr. Thus it was thought that Co exhibited high mobility but was readily excreted rather than absorbed, whereas Cr exhibited low mobility and, although it was excreted, it remained essentially local to the implant. No longer can these views be considered correct. Our results for the biologicaf trace element Zn are in keeping with those of Lux and Zeisler4’ who noted a marked decrease of this element in ‘metallosis’ tissue, i.e. tissue affected by metal released from an implant, in their

published results:

Our study of metal in the organs following total hip replacement is, we believe, the first of its kind with the exception of the study of Co by Jones et al.’ 1 Our values for this element are comparable with theirs (Table 2) and our values for Cr, MO and to a lesser extent Ni are of particular interest because of the high levels obtained. Our results for adjacent tissue on the metal-on-metal side can be compared with published values given in Table 1. It can be seen that the values obtained in the present study are greater than two1o*1t but are less than two others3gr40. It is perhaps surprising that our resufts are not greater than all those obtained previously, since the period of implantation was greater, as was most probably the wear rate. This anomaly can best be explained in terms of the lack of adequate information provided in the articles as evident from the table. Similarly, our decrease in Co and Cr concentration with increasing distance from the implant (Figure 4) is similar to the decrease in the levels of Fe, Cr. Ni and MO observed in the vicinity of stainless steel fixation devices4’*42. Our values for Co and Cr in the hair and urine are greater than those obtained by Coleman, Herrington and Scales20. Our value for Cr in the hair is similar to the normal value reported by Owen, Meachim and Williams*‘, but is *This patient was included and Scales20.

77.3

in the study of Coleman.

Vol I October

Herrington

I!

I

Figure 3 Radial section through acetabulum in to pieces

0

1

after sub-division

3

2

Distance from edge o’ c-s :cm

1

Figure 4 Variation of Co and Cr concentrarion with distance from the metal cup rim. A = Cr (canceilous bone) 3 = Cr /cortical bone) C = Cr Ibone, m/p side) 0 - Co (cancelloos bone) E = Co 6zortical bone)

Metal

Table 8

Metal concentration

in normal human organs, ‘Standard

co Lung Kidney Liver Spleen

Man’80%

Range values34

ion release:

H.S. Dobbs and M.J.

Minski

(ppm wet weight)

Cr

MO

Ni

Fe

Zn

0.001 a.048 0.001 a.044 0.001~.045

0.216.58 0.4-l .8 0.046.07

0.04-0.23 0.056.14 0.05-0.17 0.05-0.08

38.7-l 19 72.2322 122667

35.580.6 27.2-77.8 13.9-27.2

case stainless steel. They suggested that this decrease may result from a displacement of the enzyme bonded Zn by the components of the implant, causing changes in the enzymatic processes governing the development of metallosis. This decrease they associated with an increase in iron, but our results imply that it may be associated with other elements as well.

the Institute Librarians and the Department of Medical Records. We are also grateful to Mr. M. Kerridge, Director of the University of London Reactor Centre. Finally, we are grateful to Mr. J.N. Wilson for allowing us to review this case and to the patient’s relatives whose interest and generosity made this research possible.

REFERENCES DISCUSSION The values reported for the organs are of particular interest as stated above because of the high levels obtained. But were these levels the normal levels for this person? It must be recognised that for any normally occurring metal in any tissue the values observed in a population of normal people will vary over a considerable range and it has been suggested at a working rule that the upper limit of the range will be three times the mean45. This being so the values for Co and Cr obtained in this study are typically one order of magnitude greater than the upper limit of the range, and would not normally occur by chance. This conclusion is supported by ‘Standard Man’ data given in Table 8, showing the range of values occurring in normal people. What then is the significance of such high levels? There is relatively little information on the pathological effects in man of increases in the systemic load of metals, whether physiologically important or not. Certain well known cases are often cited in the literature, namely the Co related myocardiopathy in beer drinkersa and the high concentrations of Fe in Bantu tribesmen47. Also certain diseases are thought to be associated with high doses, namely for Co: thyroid hypofunction, polycythaemia and myocardiopathy, and for Cr: liver and kidney disease and carcinoma. Fe and Zn are also associated with various conditions, whereas Ni and MO are thought to be relatively non-toxic31*48. In view of the general lack of information, the amount of Co and Cr which can be taken with impunity by normal individuals cannot yet be specified, nor can the risk associated with the levels existing after long term implantation. Because of this state of uncertainty, a cautious approach can be recommended. For instance it would no doubt be prudent to use metal-on-plastic joints, instead of the now obsolete metal-on-metal ones. Even so, for metal-on-plastic joints the levels which occur in the long term are unknown, and it would be unwise at this stage to assume that they were safe.

ACKNOWLEDGEMENTS We are grateful to the following at the Institution of Orthopaedics and the Royal National Orthopaedic Hospital: Professor J.T. Scales, Dr. K.W.J. Wright, Miss Mary Wait, Mrs Sheila Barnett, Dr. G.D. Winter, Mr. J. Fincham, Dr. J. Cook, Mrs Lesley Davis, Mr. E. Andrews, Miss Beverley Coates, the Department of Medical Photography,

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36

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Biomaterials

1980,

Vol I October

197

Metal

ion release:

H.S. Dobbs end M.J.

Minski

Presented in part et the World Bioma terials Congress, Baden, April 37

38 39 40

41

798

1980

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