32 Ac a O hopaedica 2014; 85 (1): 32–38
Cance incidence and cause-speci ic mo ali y in pa ien s
wi h me al-on-me al hip eplacemen s in Finland
A popula ion-based s udy wi h a mean ollow-up o 4.6 (1–11) yea s
Keijo T Mäkelä1, Tuomo Visu i2, Pekka Pulkkinen2, An i Eskelinen3, Ville Remes4, Pe i Vi olainen1,
Mika Junnila1, and Ee o Pukkala5
1Depa men o O hopaedics and T auma ology, Su gical Hospi al, Tu ku Uni e si y Hospi al, Tu ku; 2Hjel Ins i u e, Helsinki Uni e si y, Helsinki; 3Coxa
Hospi al o Join Replacemen , Tampe e; 4Depa men o O hopaedics and T auma ology, Peijas Hospi al, Helsinki Uni e si y Cen al Hospi al, Helsinki;
5School o Heal h Sciences, Uni e si y o Tampe e, Tampe e and he Finnish Cance Regis y, Ins i u e o S a is ical and Epidemiological Cance
Resea ch, Helsinki, Finland.
Co espondence: keijo.makela@ yks. i
Submi ed 13-07-24. Accep ed 13-11-11
Open Access - This a icle is dis ibu ed unde he e ms o he C ea i e Commons A ibu ion Noncomme cial License which pe mi s any noncomme cial use,
dis ibu ion, and ep oduc ion in any medium, p o ided he sou ce is c edi ed.
DOI 10.3109/17453674.2013.878830
Backg ound and pu pose — Me al-on-me al hip implan s ha e
been widely used, especially in he USA, Aus alia, England
and Wales, and Finland. We assessed isk o dea h and upda ed
da a on he isk o cance ela ed o me al-on-me al hip eplace-
men s.
Pa ien s and me hods — A coho o 10,728 me al-on-me al
hip eplacemen pa ien s and a e e ence coho o 18,235 con-
en ional o al hip eplacemen pa ien s we e ex ac ed om
he Finnish A h oplas y Regis e o he yea s 2001–2010. Da a
on inciden cance cases and causes o dea h un il 2011 we e
ob ained om he Finnish Cance Regis y and S a is ics Fin-
land. The ela i e isk o cance and dea h we e exp essed as
s anda dized incidence a io (SIR) and s anda dized mo ali y
a io (SMR). SIR/SIR a ios and SMR/SMR a ios, and Poisson
eg ession we e used o compa e he cance isk and he isk o
dea h be ween coho s.
Resul s — The o e all isk o cance in he me al-on-me al
coho was no highe han ha in he non-me al-on-me al coho
(RR = 0.91, 95% CI: 0.82–1.02). The isk o so - issue sa coma
and basalioma in he me al-on-me al coho was highe han in
he non-me al-on-me al coho (SIR/SIR a io = 2.6, CI: 1.02–6.4
o so - issue sa coma; SIR/SIR a io = 1.3, CI: 1.1–1.5 o basali-
oma). The o e all isk o dea h in he me al-on-me al coho was
less han ha in he non-me al-on-me al coho (RR = 0.78, CI:
0.69–0.88).
In e p e a ion — The o e all isk o cance o isk o dea h
because o cance is no inc eased a e me al-on-me al hip
eplacemen . The well-pa ien e ec and selec ion bias con ib-
u e subs an ially o he indings conce ning mo ali y. A h o-
cobal ism does no inc ease mo ali y in pa ien s wi h me al-on-
me al hip implan s in he sho e m. Howe e , me al-on-me al
hip implan s should no be conside ed sa e un il da a wi h longe
ollow-up ime a e a ailable.

Me al-on-me al hip implan s ha e been widely used, espe-
cially in he USA, Aus alia, England and Wales, and Fin-
land (AOANJRR 2010, NJR 2011, Cohen 2012, Seppänen
e al. 2012). The heo e ical heal h isks ela ed o ch oni-
cally ele a ed blood me al ion concen a ions induced
by abno mal wea and co osion o he me al-on-me al
implan s—apa om local symp oms a ound he ailing
implan —include sys emic symp oms o poisoning (S eens
e al. 2006, Oldenbu g e al. 2009, Rizze i e al. 2009,
Towe 2010, 2012, Mao e al. 2011, So os and Towe 2013,
Zy iel e al. 2013) and ca cinogenesis (Mäkelä e al. 2012,
Smi h e al. 2012, B ews e e al. 2013). Sys emic me al
ion oxici y cases due o a ailed hip eplacemen a e a e.
Howe e , he e ha e been se e al ecen epo s o sys emic
cobal oxici y ollowing e ision o ac u ed ce amic
componen s, and also in pa ien s wi h a ailed me al-on-
me al hip eplacemen (S eens e al. 2006, Oldenbu g e al.
2009, Rizze i e al. 2009, Towe 2010, 2012, Mao e al.
2011, So os and Towe 2013, Zy iel e al. 2013). Possible
clinical indings include a igue, weakness, hypo hy oid-
ism, ca diomyopa hy, polycy hemia, isual and hea ing
impai men , cogni i e dys unc ion, and neu opa hy. Fa al
ca diomyopa hy due o sys emic cobal oxici y a e hip
eplacemen has been epo ed (Zy iel e al. 2013).
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Ac a O hopaedica 2014; 85 (1): 32–38 33
Me al deb is om hip eplacemen may be associa ed wi h
ch omosomal abe a ions and DNA damage (Case e al. 1996,
Bonassi e al. 2000, Daley e al. 2004). Howe e , he isk o
cance is no inc eased a e con en ional me al-on-polye h-
ylene o al hip eplacemen o a e i s -gene a ion me al-on-
me al o al hip a h oplas y (Visu i e al. 1996, 2010a). The
sho - e m o e all cance isk a e mode n me al-on-me al
hip a h oplas y is no inc eased ei he (Mäkelä e al. 2012,
Smi h e al. 2012, B ews e e al. 2013). Howe e , ecen link-
age s udies o o e all cance isk a e based on hospi al episode
s a is ics, which may ha e less quali y assu ance han cance
egis y da a (Smi h e al. 2012, B ews e e al. 2013). Annual
upda ing o cance egis y da a conce ning he me al-on-
me al issue is ad isable.
In his pape , we upda e ou ea lie published esul s on isk
o cance (Mäkelä e al. 2012) and gi e an assessmen o he
o e all and cause-speci ic mo ali y in p ima y me al-on-me al
and non-me al-on-me al hip eplacemen pa ien s who we e
ope a ed on om 2001 o 2010, by combining da a om he
Finnish A h oplas y Regis e , he Popula ion Regis e Cen e,
and he Finnish Cance Regis y. The eason o his ea ly
upda ing o he cance da a was o be able o de ec a cance o-
genic e ec o me al-on-me al implan s as ea ly as possible.
Pa ien s and me hods
The me al-on-me al coho consis ed o 10,728 pa ien s and
he non-me al-on-me al coho consis ed o 18,235 pa ien s
(Mäkelä e al. 2012). Fo de ails, see Mäkelä e al. (2012).
None o he subjec s we e los o ollow-up.
Follow-up and s a is ical analysis
The pa ien s we e ollowed up om he da e o he i s hip
eplacemen un il dea h, o un il Decembe 31, 2011. The da a
om he Finnish A h oplas y Regis e we e linked wi h he
da a om he Finnish Cance Regis y (Teppo e al. 1994)
using he unique pe sonal iden i y codes o he pa ien s. Da es
o dea h o emig a ion and causes o dea h we e ob ained om
S a is ics Finland. The Finnish Cance Regis y co e s mo e
han 99% o all cance cases in Finland (Teppo e al. 1994).
De e mina ion o he cause o dea h is based on he medical o
o ensic e idence, which p o ides he g ounds o issue o a
dea h ce i ica e. Fo ensic de e mina ion o he cause o dea h
may be necessa y i he dea h is no he esul o an illness,
i i is acciden al o iolen , o i i is caused by a ea men
p ocedu e o an occupa ional disease. In mos o he cases, he
dea h ce i ica e is based on medical e idence (S a is ics Fin-
land 1999).
The numbe s o obse ed cases o each cance ca ego y
and o each cause o dea h ca ego y and pe son-yea s a ol-
low-up we e s a i ied by sex, calenda pe iod (2001–2005 and
2006–2011), 5-yea age g oup, and ollow-up ime since he
ope a ion (< 5 yea s and ≥ 5 yea s). The expec ed numbe o
cance and he numbe o pa ien s expec ed o die om each
cause we e calcula ed by applying he numbe o pe son-
yea s in each s a um o he co esponding cance incidence
a e and mo ali y a e, espec i ely, in he Finnish popula-
ion. The ela i e isk o cance o dea h was exp essed as he
a io o he obse ed and expec ed numbe o cases, i.e. s an-
da dized incidence a io (SIR) o s anda dized mo ali y a io
(SMR). Risk a io o he 2 SIRs (SIR/SIR a io) was used o
compa ison o he me al-on-me al coho and he non-me al-
on-me al coho . The 95% con idence in e als (CIs) we e
de ined assuming ha he numbe o obse ed cases ollowed
a Poisson dis ibu ion. A Poisson eg ession analysis o u he
compa e he cance isk in he me al-on-me al and non-me al-
on-me al coho s was pe o med o all cance s and o colon
cance , p os a e cance , lung cance , and basalioma. These
cance ypes we e included in he eg ession analysis because
he numbe o cases was su icien . A Poisson eg ession
model was also used o compa ison o he isk o dea h in he
me al-on-me al coho and in he non-me al-on-me al coho .
In Poisson eg ession analyses, age was s a i ied in 30-yea
ca ego ies and ollow-up ime was s a i ied in 3 ca ego ies
( o cance : < 2, 2–5, and > 5 yea s since he ope a ion; and o
dea h: < 1, 1–5, and > 5 yea s since he ope a ion). In addi ion,
sex was added in he model.
Resul s
The me al-on-me al coho ga e 48,978 pe son-yea s and he
non-me al-on-me al coho ga e 108,904 pe son-yea s (Table
1). The mean ollow-up o he me al-on-me al coho was 4.6
(1–11) yea s and ha o he non-me al-on-me al coho was
6.0 (1–11) yea s.
Cance incidence
The o e all cance isk in he me al-on-me al coho was no
highe han ha in he Finnish popula ion (Table 2). In he
eg ession model, he o e all cance isk in he me al-on-me al
coho was no any highe han ha in he non-me al-on-me al
coho (RR = 0.9, CI: 0.8–1.0; p = 0.1).
Risk o basalioma in he me al-on-me al coho was highe
han in he Finnish popula ion (SIR = 1.4, CI: 1.2–1.6;
p < 0.001) (Table 2). Risk o basalioma in he me al-on-me al
coho was also highe han in he non-me al-on-me al coho ,
bo h in he non-s a i ied analysis (SIR/SIR a io = 1.3, CI:
1.1–1.5) (Table 3) and in he s a i ied eg ession analysis
(RR = 1.3, CI: 1.1–1.5; p = 0.01).
The SIR o skin melanoma in he me al-on-me al coho was
1.1 (CI: 0.67–1.7) and ha in he non-me al-on-me al coho
was 1.3 (CI: 1.0–1.7) ela i e o he Finnish popula ion (Table
2). Risk o melanoma in he me al-on-me al coho was no
any highe han in he non-me al-on-me al coho , bo h in he
non-s a i ied eg ession analysis (Table 3) and in he s a i ied
eg ession analysis (RR = 0.8, CI: 0.5–1.4; p = 0.4).
Downloaded by [Tampe e Uni e si y] a 02:14 23 June 2016
34 Ac a O hopaedica 2014; 85 (1): 32–38
7 so - issue sa comas we e ound in he me al-on-me al
coho du ing he ollow-up pe iod (SIR = 2.1, CI: 0.9–4.4)
(Table 2). The isk o so - issue sa coma in he me al-on-
me al coho was highe han in he non-me al-on-me al coho
(RR = 2.6, CI: 1.0–6.4) (Table 3). 2 new so - issue sa comas
we e diagnosed in 2011 in he me al-on-me al coho , a e he
closing yea (2010) o he ea lie analysis o he same coho
(Mäkelä e al. 2012). A 66-yea -old male pa ien wi h a Biome
ReCap-Magnum THA inse ed in bo h hips in 2005 was ope -
a ed o a e ope i oneal low-g ade liposa coma ixed o he
igh ileopsoas muscle (8 kg in weigh and 30 cm in diame e ).
A 64-yea -old male pa ien wi h an ASR esu acing inse ed
in his le hip in 2004 was ope a ed o a low-g ade liposa -
coma o he le adduc o lodge in 2011.
In he eg ession analysis, he isks o lung cance (RR =
0.9, CI: 0.7–1.3; p = 0.7), p os a e ca cinoma (RR = 1.1, CI:
0.9–1.4; p = 0.4), and colon ca cinoma (RR = 1.0, CI: 0.6–1.7;
p = 1.0) we e no signi ican ly di e en in he me al-on-me al
coho and he non-me al-on-me al coho .
Mo ali y
The all-cause SMR was 0.65 (CI: 0.58–0.71) o he me al-
on-me al coho and 0.72 (CI: 0.70–0.75) o he non-me al-
on-me al coho , as compa ed o he Finnish popula ion (Table
4). The o e all isk o dea h in he me al-on-me al coho was
less han ha in he non-me al-on-me al coho (RR = 0.78,
CI: 0.69–0.88; p < 0.001). SMRs o dea hs a e p esen ed in
he Figu e. SMR was s a is ically signi ican ly less han in he
Table 1. Numbe o pa ien s (n) acco ding o age a ope a ion, and numbe o pe son-yea s acco ding o he age
a ollow-up. The non-me al-on-me al coho consis ed o implan s wi h me al-on-polye hylene, ce amic-on-
polye hylene, and ce amic-on-ce amic bea ing su aces
Me al-on-me al (MoM) coho Non-me al-on-me al coho
Men Women Men Women
Age n Pe son-yea s n Pe son-yea s n Pe son-yea s n Pe son-yea s
< 20 6 14 3 16 – – – –
20–29 25 101 16 56 4 17 7 23
30–39 158 435 67 236 30 101 20 87
40–49 741 2,833 468 1,569 143 616 157 491
50–59 2,275 8,516 1,642 6,226 850 3,327 922 3,711
60–69 2,257 11,955 1,581 8,383 2,260 11,140 2,739 12,557
70–79 762 4,599 594 3,263 3,044 19,193 5,394 29,603
≥ 80 65 430 48 346 697 7,844 1,953 20,193
To al 6,289 28,884 4,419 20,094 7,028 42,239 11,192 66,665
Table 2. Obse ed numbe s o cance cases, he expec ed numbe s o cance cases app oxima ed om he Finnish popu-
la ion, and s anda dized incidence a ios wi h 95% con idence in e als—acco ding o si e—a e gi en o he me al-on-
me al coho and o he non-me al-on-me al coho . The la e coho consis ed o implan s wi h me al-on-polye hylene,
ce amic-on-polye hylene, and ce amic-on-ce amic bea ing su aces
MoM coho Non-MoM coho
P ima y si e Obs Exp SMR 95% CI Obs Exp SMR 95% CI
All si es 497 534 0.93 0.85–1.01 1952 1908 1.02 0.98–1.06
S omach 13 12 1.08 0.57–1.84 57 53 1.07 0.81–1.39
Colon 20 29 0.69 0.42–1.05 118 132 0.89 0.74–1.06
Lung 32 53 0.61 0.41–0.85 b 126 181 0.70 0.58–0.82 c
Co pus u e i 14 13 1.08 0.59–1.81 61 58 1.05 0.80–1.35
P os a e 135 124 1.09 0.91–1.27 334 334 1.00 0.90–1.10
Kidney 16 18 0.91 0.52–1.47 62 61 1.01 0.77–1.29
Bladde 11 18 0.61 0.30–1.08 80 71 1.12 0.89–1.39
So - issue sa coma 7 3 2.14 0.86–4.40 11 12 0.95 0.47–1.69
Non-Hodgkin lymphoma 17 21 0.82 0.48–1.31 81 73 1.11 0.88–1.38
Hodgkin lymphoma 1 1 0.79 0.02–4.40 1 3 0.35 0.01–1.92
Mul iple myeloma 5 6 0.79 0.26–1.83 28 28 1.02 0.68–1.47
Leukemia 7 9 0.75 0.30–1.55 38 38 1.00 0.71–1.37
Melanoma 21 19 1.09 0.67–1.65 73 56 1.30 1.02–1.63 a
Basalioma 178 132 1.35 1.16–1.55 c 626 586 1.07 0.99–1.15
Obs: obse ed numbe o cance cases; Exp: expec ed numbe o cance cases om he Finnish popula ion;
SIR: s anda dized incidence a io; CI: con idence in e al.
a p < 0.05, b p < 0.01, c p < 0.001.
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Ac a O hopaedica 2014; 85 (1): 32–38 35
Finnish popula ion du ing he i s 4 pos ope a i e ollow-up
yea s in he me al-on-me al coho and du ing he i s 7 pos -
ope a i e yea s in he non-me al-on-me al coho .
The SMR o ca dio ascula dea hs was 0.67 (CI: 0.56–0.78)
in he me al-on-me al coho and 0.74 (CI: 0.70–0.78) in he
non-me al-on-me al coho , ela i e o he Finnish popula ion
(Table 4). The SMR o ca dio ascula dea hs in a ollow-up
ime o 5 yea s o mo e since ope a ion was 0.81 (CI: 0.50–
1.2) in he me al-on-me al coho and 0.98 (CI: 0.90–1.1) in
he non-me al-on-me al coho ela i e o ha in he Finnish
popula ion. The sepa a ely analyzed SMR o ischemic hea
disease dea hs in a ollow-up ime o 5 yea s o mo e since
ope a ion was 0.77 (CI: 0.40–1.34) in he me al-on-me al
coho and 0.90 (CI: 0.80–1.01) in he non-me al-on-me al
coho ela i e o ha in he Finnish popula ion. The isk o
ca dio ascula dea hs in he me al-on-me al coho was less
han ha in he non-me al-on-me al coho (RR = 0.79, CI:
0.64–0.97; p = 0.02). Sepa a ely analyzed isk o ischemic
hea disease dea hs in he me al-on-me al coho was no any
highe han in he non-me al-on-me al coho (RR = 0.78, CI:
0.60–1.02; p = 0.07).
The isk o dea h om cance in he me al-on-me al coho
was less han in he non-me al-on-me al coho (RR = 0.78,
CI: 0.63–0.97; p = 0.02). The isks o dea h om espi a o y
disease and o dea h om acciden s and iolence in he me al-
on-me al coho we e simila o hose in he non-me al-on-
me al coho (RR = 0.86, CI: 0.42–1.74; p = 0.7; and RR =
0.92, CI: 0.61–1.39; p = 0.7, espec i ely).
The only s a is ically signi ican in e ac ion in he ca ego y
eg ession analysis was ha o implan ype and sex in dea hs
om all causes (p = 0.01). The isk a io o male pa ien s in
he me al-on-me al coho was 0.70 (CI: 0.60–0.82) and o
emale pa ien s in his coho i was 0.98 (CI: 0.78–1.2).
Table 3. SIR/SIR a ios o he me al-on-me al g oup and
he non-me al-on-me al g oup (consis ing o implan s
wi h me al-on-polye hylene, ce amic-on-polye hylene,
and ce amic-on-ce amic bea ing su aces) wi h 95%
con idence in e als, acco ding o si e
P ima y si e SIR/SIR a io 95% CI
All si es 0.91 0.82–1.00
S omach 1.01 0.56–1.82
Colon 0.77 0.48–1.23
Lung 0.87 0.59–1.28
P os a e 1.09 0.89–1.33
Kidney 0.87 0.51–1.51
Bladde 0.54 0.29–1.01
U e us 1.02 0.58–1.82
So issue 2.55 1.02–6.36
Non-Hodgkin lymphoma 0.73 0.44–1.22
Hodgkin lymphoma 3.00 0.31–28.7
Mul iple myeloma 0.83 0.33–2.09
Leukemia 0.78 0.35–1.71
Melanoma 0.85 0.52–1.37
Skin, basal cell ca cinoma 1.26 1.07–1.49
SIR: S anda dized incidence a io.
Table 4. Obse ed and expec ed numbe s o dea hs, and s anda dized mo ali y a ios o he me al-on-me al and non-
me al-on-me al coho s in he main disease g oups
MoM coho Non-MoM coho
Cause o dea h Obs Exp SMR 95% CI Obs Exp SMR 95% CI
Cance 114 173 0.66 0.55–0.78 c 764 873 0.87 0.81–0.93 c
Ca dio ascula 131 196 0.67 0.56–0.78 c 1,274 1,719 0.74 0.70–0.78 c
Respi a o y 11 25 0.44 0.22–0.78 b 84 204 0.41 0.33–0.50 c
Acciden s and iolence 45 46 0.97 0.71–1.29 180 158 0.82 0.69–0.97 a
All causes 365 562 0.65 0.58–0.71 c 2,785 3,846 0.72 0.70–0.75 c
MoM: me al-on-me al; Obs: obse ed numbe o dea hs; Exp: expec ed numbe o dea hs; SMR: s anda dized mo ali y a io;
CI: con idence in e al.
a p < 0.05, b p < 0.01, c p < 0.001.
S anda dized mo ali y a ios (SMRs) o dea hs om all diseases in
annual ollow-up o me al-on-me al (MoM) and non-me al-on-me al
(non-MoM) coho s.
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36 Ac a O hopaedica 2014; 85 (1): 32–38
Discussion
The main inding o his s udy was ha he o e all isk o
cance was no highe han in he non-me al-on-me al coho .
This inding is in acco dance wi h p e ious indings (Visu i e
al. 1996, 2010a, Onega e al. 2006, Smi h e al. 2012, Mäkelä
e al. 2012, B ews e e al. 2013). Pa ien selec ion—i.e. he
heal hy-pa ien e ec —had an app eciable in luence on o e -
all and si e-speci ic isk o dea h du ing he i s yea s o
ollow-up, bo h in he me al-on-me al and in he non-me al-
on-me al coho s. The o e all and si e-speci ic isk o dea h
was no highe in he me al-on-me al coho han in he non-
me al-on-me al coho , no e en a e he pa ien selec ion
bias had ceased a e he i s 5 yea s o ollow-up. The ind-
ings conce ning isk o dea h ag ee wi h p e iously published
esul s (Visu i e al. 1994, 2010b, Lie e al. 2000, Ramiah e
al. 2007, McMinn e al. 2012). The isk o so - issue sa coma
and basalioma in he me al-on-me al coho was highe han
in he non-me al-on-me al coho , as in ou p e ious epo
(Mäkelä e al. 2012). 2 liposa comas a he si e o me al-on-
me al hip eplacemen we e ound in 2011 in Finland. The
isk o so - issue sa coma and basalioma may be ele a ed by
chance alone.
S eng hs and limi a ions o he s udy
One s eng h o he p esen s udy was he popula ion-based
design, wi h high numbe s o pa ien s wi h me al-on-me al hip
implan . We we e able o assess mo ali y acco ding o cause
o dea h, and o de e mine he incidence o di e en cance
ypes by combining da a om he Finnish A h oplas y Reg-
is e and he Finnish Cance Regis y. One weakness was he
sho ollow-up ime. Ano he weakness was he lack o in o -
ma ion on po en ial con ounding ac o s ega ding mo ali y
and cance isk. Fu he mo e, he supposed sys emic compli-
ca ions om me al-on-me al eplacemen s, such as ca diomy-
opa hy, a e a e. The abili y o egis y da a o pinpoin dea hs
om ca diomyopa hy may be inadequa e.
Compa ison wi h o he s udies
The long- e m o e all isk o dea h was no inc eased using
i s -gene a ion me al-on-me al hip implan s (Visu i e al.
2010b). The 10-yea li e expec ancy o con en ional o al hip
a h oplas y pa ien s is highe han ha o he gene al popula-
ion (Visu i e al. 1994, Lie e al. 2000, Ramiah e al. 2007).
Male pa ien s wi h me al-on-me al Bi mingham hip esu ac-
ing had a lowe isk o dea h han hose wi h a con en ional
hip de ice (McMinn e al. 2012). Howe e , he Bi mingham
hip esu acing pa ien s we e younge and heal hie han
hose wi h a con en ional hip eplacemen . These indings by
McMinn e al. a e in acco dance wi h ou da a. Pa ien selec-
ion, i.e. he heal hy-pa ien e ec , p obably explains a majo
pa o he be e su i al o hip eplacemen pa ien s com-
pa ed o he s anda d popula ion. Ca dio ascula dea hs due
o cobal ism associa ed wi h me al-on-me al hip implan s a e
a e and excep ional (Zy iel e al. 2013). Mos a h op os-
he ic cobal ism cases a e p obably cu able when he implan
has been e ised, and canno he e o e be de ec ed on he basis
o mo ali y da a.
The cance isk o he pa ien s wi h i s -gene a ion me al-
on-me al o al hip a h oplas y was no ele a ed, e en in long-
e m ollow-up (Visu i e al. 1996). Using hospi al discha ge,
cance , and mo ali y eco ds, B ews e e al. (2013) s udied
he incidence o cance in 1,317 me al-on-me al esu acing
a h oplas y pa ien s in Sco land who we e ope a ed be ween
2000 and 2009. The isk o cance s o e all (n = 39) was no
inc eased (B ews e e al. 2013). Smi h e al. (2012) s udied
40,576 hip eplacemen pa ien s wi h me al-on-me al bea ing
su aces and 248,995 wi h al e na i e bea ings, based on da a
om he Na ional Join Regis y o England and Wales and
hospi al episode s a is ics. Compa ed o al e na i e bea ings,
he e was no e idence ha me al-on-me al bea ing su aces
we e associa ed wi h an inc eased o e all isk o cance (a e
a mean ollow-up o 3 yea s). The e was no inc ease in he isk
o malignan melanoma o hema ological, p os a e, and enal
ac cance s ei he . Fu he mo e, he o e all cance isk in
ou me al-on-me al coho was no inc eased in ou p e ious
epo co e ing pa ien s ope a ed du ing he yea s 2001–2010
who we e ollowed un il 2010 (Mäkelä e al. 2012). All hese
p e ious indings a e in acco dance wi h ou cu en indings
wi h a ollow-up ime un il he end o 2011.
The isk o so - issue sa coma in he me al-on-me al coho
was inc eased in ou p e ious epo , bu no s a is ically sig-
ni ican ly (Mäkelä e al. 2012). In he linkage s udy based on
da a om he Na ional Join Regis y o England and Wales
and hospi al episode s a is ics (Smi h e al. 2012), sa coma
isk associa ed wi h me a-on-me al hip eplacemen s was
no analyzed sepa a ely. In ou wo k, 2 new sa coma cases
we e diagnosed in he me al-on-me al coho in 2011 a e
he p e ious analysis based on ollow-up da a un il 2010.
To ou knowledge, he 2 liposa comas diagnosed in 2011 in
Finland a e he i s desc ip ions o liposa coma a he si e o
a me al-on-me al hip implan . S ephensen e al. (1999) pub-
lished a case epo o a liposa coma in he adduc o lodge in a
57-yea -old male heuma oid pa ien wi h a con en ional o al
hip a h oplas y. Howe e , he o al numbe o sa coma cases
in ou s udy was small. The inc eased incidence o sa comas
in he me al-on-me al coho may s ill be a chance inding.
Hund eds o housands o me al-on-me al hip eplacemen s
ha e been pe o med wo ldwide, bu only 5 malignan local
umo s a he si e o i s -gene a ion me al-on-me al eplace-
men s ha e been epo ed p e iously (Visu i e al. 2006).
A isk o melanoma has been associa ed wi h con en ional
o al hip a h oplas y in some o he ea lie s udies (Ny en
e al. 1995, Olsen e al. 1999, Visu i e al. 2003, 2006) bu
no all o hem (Visu i e al. 2010a). Incidence o melanoma
was ound o be inc eased in pa ien s wi h a con en ional hip
implan inse ed du ing 2005–2009 in Sco land (SIR = 1.4,
CI: 1.1–1.9), bu no in pa ien s wi h a me al-on-me al hip
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Ac a O hopaedica 2014; 85 (1): 32–38 37
esu acing de ice (B ews e e al. 2013). The incidence o
melanoma in he non-me al-on-me al coho in he cu en
s udy was highe han in he Finnish gene al popula ion, as
also ound in ou p e ious epo (Mäkelä e al. 2012). Mela-
noma isk in he me al-on-me al coho was simila o ha in
he non-me al-on-me al coho . The inc eased incidence o
melanoma in he non-me al-on-me al coho may ha e been
due o su ey bias. In he s udy based on he Na ional Join
Regis y o England and Wales, he isk o melanoma was no
highe in me al-on-me al pa ien s han in pa ien s wi h o he
bea ing op ions in he i s 7 yea s a e a h oplas y (Smi h
e al. 2012). Howe e , he assessmen o ou come was based
on linkage o hospi al episode s a is ics, which may ha e been
associa ed wi h less quali y assu ance han da a om a cance
egis y. In o ma ion on some cance s may ha e been missing,
e.g. cu aneous melanoma, which does no necessa ily lead o
hospi al admission (Smi h e al. 2012, B ews e e al. 2013).
The me al-on-me al coho showed a highe isk o basali-
oma han he non-me al-on-me al coho , which is in acco -
dance wi h ou p e ious epo (Mäkelä e al. 2012). Basalioma
incidence was inc eased in he pa ien s wi h a con en ional
hip implan inse ed du ing 2005–2009 in Sco land (SIR =
1.1, CI: 1.0–1.2), bu no in pa ien s wi h a me al-on-me al hip
esu acing (B ews e e al. 2013). In o he p e ious s udies on
o al hip eplacemen pa ien s, basalioma was ei he no egis-
e ed a all o was included in he ca ego y o o he skin can-
ce s (Visu i e al. 2006, Smi h e al. 2012). In heo y, le els o
me al ions in he skin could be ele a ed a e me al-on-me al
hip eplacemen , pe haps causing DNA damage oge he wi h
ul a iole adia ion. Howe e , we a e no awa e o any s udies
ha ha e been conduc ed o add ess his issue.
KTM, TV, PP, and EP designed he p o ocol. KTM, TP, TV, and KTM ana-
lyzed he da a. KTM, TV, PP, AE, VR, PV, MJ, and EP w o e he manusc ip .
This s udy was unded by a Tu ku Uni e si y Hospi al Resea ch G an and an
O ion-Fa mos Resea ch Founda ion G an .
No compe ing in e es s decla ed.
Aus alian O hopaedic Associa ion. Na ional Join Replacemen Regis y
(AOANJRR). Annual Repo 2010.
Bonassi S, Hagma L, S ömbe g U, Mon agud A H, Tinne be g H, Fo ni
A, e al. Ch omosomal abe a ions in lymphocy es p edic human cance
independen ly o exposu e o ca cinogens. Eu opean S udy G oup on Cy o-
gene ic Bioma ke s and Heal h. Cance Res 2000; 60: 1619-25.
B ews e D H, S ock on D L, Reekie A, Ashc o G P, Howie C R, Po e D
E, Black R J. Risk o cance ollowing p ima y o al hip eplacemen o
p ima y esu acing a h oplas y o he hip: a e ospec i e coho s udy in
Sco land. B J Cance 2013; 108 (9): 1883-90. doi: 10.1038/bjc.2013.129.
Case C P, Langkame V G, Howell R T, Webb J, S anden G, Palme M, e
al. P elimina y obse a ions on possible p emalignan changes in bone
ma ow adjacen o wo n o al hip a h oplas y implan s. Clin O hop
(Suppl) 1996; (329): 269-79.
Cohen D. How sa e a e me al-on-me al hip implan s? BMJ 2012; 344: e1410.
Daley B, Dohe y A T, Fai man B, Case C P. Wea deb is om hip o knee
eplacemen s causes ch omosomal damage in human cells in issue cul u e.
J Bone Join Su g (B ) 2004; 86: 598-606.
Lie S A, Engesae e L B, Ha elin L I, Fu nes O, Vollse S E. Mo ali y a e
o al hip eplacemen : 0-10-yea ollow up o 39,543 pa ien s in he No we-
gian A h oplas y Regis e . Ac a O hop Scand 2000; 71: 19-27.
Mao X, Wong A A, C aw o d R W. Cobal oxici y – an eme ging clinical
p oblem in pa ien s wi h me al-on-me al hip P oh heses? Med J Aus 2011;
194: 649-51.
McMinn D J W, Snell K I E, Daniel J, T eacy R B C, Pynsen P B, Riley
R D. Mo ali y and implan e ision a es o hip a h oplas y in pa ien s
wi h os eoa h i is: egis y based coho s udy. BMJ 2012; 344: e3319 doi:
10.1136/bmj.e3319
Mäkelä K T, Visu i T, Pulkkinen P, Eskelinen A, Remes V, Vi olainen P, Jun-
nila M, Pukkala E. Risk o cance wi h me al-on-me al hip eplacemen s:
popula ion based s udy. BMJ 2012; 345: e4646 doi: 10.1136/bmj.e4646
Na ional Join Regis y o England and Wales (NJR England-Wales). 8 h
Annual Repo 2011.
Ny en O, McLaughlin J K, G idley G, Ekbom A, Johnell O J, F aumeni J F,
e al. Cance isk a e hip eplacemen wi h me al implan s: a popula ion-
based coho s udy in Sweden. J Na l Cance Ins 1995; 87 (1): 28-33.
Oldenbu g M, Wegne R, Bau X. Se e e cobal in oxica ion due o p os hesis
wea in epea ed o al hip a h oplas y. J A h oplas y 2009; 24: e15-e20.
Olsen J O, McLaughlin J K, Ny en O, Mellamkjae L, Lipwo h L, Blo W
J, e al. Hip and knee implan a ions among pa ien s wi h os eoa h i is and
isk o cance : a eco d-linkage s udy om Denma k. In J Cance 1999;
81: 719-22.
Onega T, Ba on J, MacKenzie T. Cance a e o al join a h oplas y: a me a-
analysis. Cance Epidemiol Bioma ke s P e 2006; 15: 1532-7.
Ramiah R D, Ashmo e A M, Whi ley E, Bannis e G C. Ten-yea li e expec-
ancy a e p ima y o al hip eplacemen . J Bone Join Su g (B ) 2007; 89:
1299-302.
Rizze i M C, Libe ini P, Za a ini G, Ca alani S, Pazzaglia U, Apos oli P,
Pado ani A. Loss o sigh and sound. Could i be he hip? Lance 2009; 21:
373(9668):1052.doi: 10.1016/S0140-6736(09)60490-6
Seppänen M, Mäkelä K, Vi olainen P, Remes V, Pulkkinen P, Eskelinen A.
Hip esu acing a h oplas y–sho e m su i o ship o 4,401 hip om he
Finnish A h oplas y Regis e . Ac a O hop 2012; 83: 207-13.
Smi h A J, Dieppe P, Po e M, Blom A W. Risk o cance in i s se en yea s
a e me al-on-me al hip eplacemen compa ed wi h o he bea ings and
gene al popula ion: linkage s udy be ween he Na ional Join Regis y o
England and Wales and hospi al episode s a is ics. BMJ 2012; 344: e2383
doi: 10.1136/bmj.e2383
So os J G, Towe S S. Sys emic disease a e hip eplacemen : ae omedical
implica ions o a h op os he ic cobal ism. A ia Space En i on Med 2013;
84: 242-5.
S a is ics Finland. Causes o dea h. Heal h 1999; 3: 18–21.
S eens W, on Foe s e G, Ka ze A. Se e e cobal poisoning wi h loss o
sigh a e ce amic-me al pai ing in a hip-a case epo . Ac a O hop 2006;
77: 830-2.
S ephensen S, Swa z Laus en G, Thomsen H S, Bje egaa d B. Liposa coma
in associa ion wi h o al hip eplacemen . In O hop 1999; 23: 187-9.
Teppo L, Pukkala E, Leh onen M. Da a quali y and quali y con ol o a popu-
la ion-based cance egis y. Expe ience in Finland. Ac a Oncol 1994; 33:
365-9.
Towe S S. A h op os he ic cobal ism: neu ological and ca diac mani es a-
ions in wo pa ien s wi h me al-on-me al A h oplas y. A case epo . J
Bone Join Su g (Am) 2010; 92: 2847-51.
Towe S S. A h op os he ic cobal ism associa ed wi h me al on me al hip
implan s. BMJ 2012; 344: e430 doi: 10.1136/bmj.e430
Downloaded by [Tampe e Uni e si y] a 02:14 23 June 2016
38 Ac a O hopaedica 2014; 85 (1): 32–38
Visu i T, Pulkkinen P, Tu ula K B, Paa olainen P, Kosken uo M. Li e expec-
ancy a e hip a h oplas y. Case-con ol s udy o 1018 cases o p ima y
a h osis. Ac a O hop Scand 1994; 65: 9-11.
Visu i T, Pukkala E, Paa olainen P, Pulkkinen P, Riska E B. Cance isk
a e me al on me al and polye hylene on me al o al hip a h oplas y. Clin
O hop (Suppl) 1996; (329): S280-9.
Visu i T, Pukkala E, Pulkkinen P, Paa olainen P. Dec eased cance isk in
pa ien s who ha e been ope a ed on wi h o al hip and knee a h oplas y o
p ima y os eoa hosis. Ac a O hop Scand 2003; 74: 351-60.
Visu i T, Pulkkinen P, Paa olainen P. Malignan umo s a he si e o o al hip
p os hesis. Analy ic e iew o 46 cases. J A h oplas y 2006; 21: 311-23.
Visu i T, Pulkkinen P, Paa olainen P, Pukkala E. Cance isk is no inc eased
a e con en ional hip a h oplas y. a na iowide s udy om he Finnish
A h oplas y Regis e wi h ollow-up o 24,636 pa ien s o a mean o 13
yea s. Ac a O hop 2010a; 81: 77-81.
Visu i T, Bo g H, Pulkkinen P, Paa olainen P, Pukkala E. A e ospec i e com-
pa a i e s udy o mo ali y and causes o dea h among pa ien s wi h me al-
on-me al and me al-on-polye hylene o al hip p os heses in p ima y os eo-
a h i is a e a long- e m ollow-up. BMC Muskuloskel Dis 2010b; 11: 78.
Zy iel M G, B and J M, O e gaa d C B, Cheung A C, Tu geon T R, Syed K
A. Fa al ca diomyopa hy a e e ision o al hip eplacemen o ac u e o
a ce amic line . Bone Join J 2013; 95: 31-7.
Downloaded by [Tampe e Uni e si y] a 02:14 23 June 2016