The Journal of Bone and Joint Surgery 83:501 (2001)

2001 The Journal of Bone and Joint Surgery, In!

Titanium Particles Stimulate Bone Resorption by
Inducing Differentiation of Murine Osteoclasts
Yanming Bi, PhD, R Renee !anDeMotter, MS, "shraf " Ragab, MD, !ictor M
#oldberg, MD, $ames M "nderson, MD, PhD and %d&ard M #reenfield, PhD
In"e#tigation $erfor%ed at the &e$art%ent# of 'rtho$aedi# and (athology, )a#e *e#tern +e#er"e
,ni"er#ity, )le"eland, 'hio
-an%ing Bi, (h& +! +enee .an &e /otter, /S 0#hraf 0! +aga1, /& .itor /! 2old1erg, /& Ja%e# /!
0nder#on, /&, (h& 3d4ard /! 2reenfield, (h& &e$art%ent# of 'rtho$aedi# (-!B!, +!+!.!&!/!, 0!0!+!,
.!/!2!, and 3!/!2!) and (athology (J!/!0!), )a#e *e#tern +e#er"e ,ni"er#ity, 11100 3ulid 0"enue,
)le"eland, '5 6610785000! 38%ail addre## for 3!/! 2reenfield: e%g39$o!4ru!edu
:o 1enefit# in any for% ha"e 1een reei"ed or 4ill 1e reei"ed fro% a o%%erial $arty related diretly or
indiretly to the #u1;et of thi# artile! <und# 4ere reei"ed in total or $artial #u$$ort of the re#earh or
linial #tudy $re#ented in thi# artile! The funding #oure# 4ere :ational In#titute# of 5ealth 2rant#
0+63=7>, 5?3386>, and 0+0=505!
Ba@ground:

?oo#ening of ortho$aedi i%$lant# i# %ediated 1y yto@ine# that eliit

1one re#or$tion
and are $rodued in re#$on#e to $hagoyto#i# of

i%$lant8deri"ed 4ear $artile#! Thi#
aelerated 1one re#or$tion ould

1e due to inrea#ed o#teola#ti ati"ity, #ur"i"al, or
differentiation! 0lthough

a nu%1er of in vitro #tudie# ha"e #ho4n that 4ear $artile#

inrea#e o#teola#ti ati"ity, the inrea#e 4a# le## than t4ofold

in all a#e#! The o1;eti"e
of the urrent #tudy 4a# to te#t

the hy$othe#i# that 4ear $artile# #ti%ulate 1one
re#or$tion

1y induing o#teola#t differentiation!

/ethod#:

)onditioned %edia 4ere $re$ared fro% %urine %arro4 ell# or

hu%an $eri$heral 1lood
%onoyte# inu1ated in the $re#ene or

a1#ene of titaniu% $artile#! The effet# of
onditioned %edia

on o#teola#t differentiation 4ere eAa%ined 4ith u#e of a reently

de"elo$ed a##ay in 4hih o#teola#t $reur#or# are o8ultured

4ith %e#enhy%al
#u$$ort ell#!

+e#ult#:

The $re#ent #tudy #ho4ed that titaniu% $artile# indued 1oth %urine

%arro4 ell# and
hu%an $eri$heral 1lood %onoyte# to $rodue fator#

that #ti%ulated o#teola#t
differentiation! The %ean inrea#e in

o#teola#t differentiation 4a# 2>!3 B >!68fold! The
#ti%ulation

of o#teola#t differentiation led to a $arallel inrea#e in

1one re#or$tion! The
a%ount of #ti%ulation 4a# regulated in

a do#e8de$endent %anner 1y the onentration of
1oth titaniu% $artile#

and onditioned %edia! The #ti%ulation of o#teola#t
differentiation reCuired

interation# 1et4een the ell# and the $artile# the%#el"e# and,

therefore, 4a# not due to %etal ion#, #olu1le onta%inant# relea#ed

fro% the $artile#, or
#u1%iro%eter $artile#! In ontra#t, onditioned

%edia fro% ontrol ell# inu1ated in
the a1#ene of titaniu%

$artile# had no deteta1le effet on any of the eAa%ined
$ara%eter#!

)onlu#ion#:

The $re#ent #tudy #ho4ed that titaniu% $artile# #ti%ulate in vitro

1one re#or$tion
$ri%arily 1y induing o#teola#t differentiation! In

ontra#t, the titaniu% $artile# had
only #%all effet# on o#teola#t ati"ity

or #ur"i"al!

)linial +ele"ane:

The $re#ent #tudy $ro"ide# #trong #u$$ort for the hy$othe#i# that

o#teola#t
differentiation i# an i%$ortant fator in the de"elo$%ent of

a#e$ti loo#ening! The
de"elo$%ent of thera$euti inter"ention# to

redue o#teola#t differentiation %ay 1e a
u#eful a$$roah for i%$ro"ing

the $erfor%ane of ortho$aedi i%$lant#!