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Biomaterials

We are focussed on understanding the interface between living and synthetic


(resorbable/man-made/artificial etc.) tissues. Part of this focus is constrained by our
belief that the ultimate resorbable substrate will be a combination of polymer and
ceramic. In the most optimistic view of hard tissue replacements the monolith must be
able to function mechanically within the body during slow and measured regeneration of
natural tissue (along with the attendant need for modulus matching). Thus the patient will
stress the implant; much of the literature demonstrates that this is necessary to promote
the development of the appropriate bone structure.
Using HA particles produced utilizing the procedure of Lazic, HA-PMMA composites
were formed using standard dental techniques. These composites were then used in
studies of osteoblast-surface interaction. The degree of interaction was assessed using a
well characterized model of osteogenesis, fetal rat calvarial osteoblasts. Osteoblasts were
isolated from 21-day-old fetal rat calvariae. Following an initial treatment of calvariae for
10 minutes at 37C with 570 U/ml collagenase (Worthington Biochemical Corp.,
Freehold, NJ), the cells released from calvariae by two 10-minute and two 20-minute
sequential collagenase digestions were pooled and then filtered through both 100 mm and
37 mm Nitex filters. Cells were grown overnight at 25,000 cells/cm2 on plastic dishes
(Corning, Corning, NY). The cells were then detached, using 0.05% trypsin and 0.53 mM
EDTA in Hanks buffered salt solution (Gibco, Grand Island, NY). Cells were plated at a
density of 36,000 cells/cm2 on both the experimental (HA-PMMA) and the control
substrates. The cells were grown in alpha-Minimum Essential Medium supplemented
with 10% heat-inactivated fetal calf serum (Gibco). After confluence (3 days) the
medium was further supplemented with freshly prepared ascorbic acid (50 mg/ml) and
-glycerophosphate (3 mM) (Sigma Chemical Co., St. Louis, MO) to trigger
differentiation (contact Amr Moursi, Moursi.1@osu.edu, if this level of detail is not
exhaustive enough). The results are pictured in Figure 1.
Overall observations showed that proliferation and attachment were similar to the control.
Matrix deposition appeared to be uniform, however the micrographs (Figure 1) show that
cell-HA interactions were extensive. Osteoblast attachment to these composites was
higher than that of PMMA or dense Ti substrates.
Figure 1a). SEM micrograph of an HA-PMMA composite surface
following a 14 day exposure to calvarial osteoblast culture. The cell layer
has been removed to allow for direct observation of the effects of exposure
on the ceramic particles. The HA is visible as irregular solid pieces in the
PMMA matrix. Fine parallel lines are an artifact of the cutting operation
used to produce this surface.
Figure 1b). Micrograph of calvarial osteoblast cell layer cultured on the
HA-PMMA composite surface for 14 days. The cell layer shows evidence
of abundant attachment, proliferation and extra-cellular matrix deposition.
Correlations between the characteristics of the overall cell layer and HA
particle location have not yet been established.
Figure 1c). Higher magnification image of an HA particle embedded in the
polymer matrix. Separation of the particle from the polymer matrix is
evident. The surface of the particle is no longer visible due to deposition
of collagen and other fibrillar and globular extra-cellular matrix
components. The PMMA surrounding the particle shows much less
evidence of matrix deposition.
Figure 1d). High magnification micrograph of the exposed particle surface
covered with a network of fibrillar and globular extra-cellular matrix
components. Clearly, matrix synthesis and deposition was very strong
during the 14 day culture period. Cross-sectional TEM studies will be
necessary to observe these cell-HA interactions at a more meaningful
level.
Bone Cells
Osteoclasts
Osteoblasts
Osteocytes
Lining cells
Bone cell origins
Local regulators
Apoptosis
Introduction
There are two categories of bone cells. Osteoclasts are in the first category. They
resorb (dissolve) the bone. The other category is the osteoblast family, which
consists of osteoblasts that form bone, osteocytes that help maintain bone, and
lining cells that cover the surface of the bone.
Osteoclasts
* . . . are large cells with many nuclei.
* . . . share lineage with blood cells
(especially macrophages).
* Precursors circulate in the blood and bone
marrow.
* Mature osteoclasts are formed from fusion
of the precursors.
* This happens when !"# receptors on the
osteoclast precursors are activated by the
!"#$ligand which was secreted by
osteoblasts.
* Osteoprotegerin (OP%) is a factor in the
marrow which also binds !"#$ligand, so it
can help to regulate the osteoclast activation.
* Osteoclasts resorb the bone. They form
sealed compartments ne&t to the bone
surface and secrete acids and en'ymes which
degrade the bone. The edge ne&t to the bone
is called the ruffled border.
* !fter they finish resorbing bone, they
undergo apoptosis (programmed cell death,
sometimes called (cell suicide(). This process
is regulated by proteins from other cells.
Move your mouse over the photomicrograph below to see labels.
This picture is from the bones of a patient with very high
parathyroid hormone (PT)), so the osteoclasts are particularly easy to see.
PT) is further discussed in the hormone section.
photo courtesy of Russ Turner
Osteoblasts
*. . . are cuboidal and columnar in shape with a central nucleus
found on the bone surface.
*%ap *unctions with neighboring osteoblasts allow cells to
communicate with each other.
*They come from bone marrow precursor cells. These precursors
are capable of turning into either osteoblasts or fat cells, and
various factors determine which +ind of cells will be made. One of
the factors is called ,bfa -, which will cause the cell to
differentiate into an osteoblast.
*The *ob of osteoblasts is to ma+e the proteins that will form the
organic matri& of bone and to control minerali'ation of the bone
*They have receptors for hormones such as vitamin ., estrogen,
and parathyroid hormone.
*They secrete factors that activate osteoclasts (!"#$ligand) and
other factors which communicate with other cells.
*They secrete P)/0, a protein that helps to regulate the amount
of phosphate e&creted by the +idney.
*1hen the team of osteoblasts has finished ma+ing new bone,
some become surrounded with matri& and differentiate into
osteocytes. Others will remain on the surface of the new bone and
differentiate into lining cells. The rest undergo apoptosis (cell
suicide) and disintegrate.
Move your mouse over the photomicrograph to see labels.
photo courtesy of Russ Turner
Osteocytes
* . . . live inside the bone and have long branches which
allow them to contact each other as well as the lining cells
on the bone surface.
* . . . are in a perfect position to sense any mechanical
strain on the bone.
* . . . can secrete growth factors which activate the lining
cells or stimulate the osteoblasts.
* Their e&act role is still under investigation, but probably
the osteocytes direct bone remodeling to accomodate
mechanical strain and repair fatigue damage.
image from Jee WSS 1983 The skeletal tissues. In: Weiss L,
ed., Histology, Cell and Tissue Biology. Elseier Biomecical,
New York, NY, USA pp.200-255. Permission pending.
Lining cells
* . . . are former osteoblasts which have become flat and panca+e$shaped.
* . . . line the entire surface of the bone.
* . . . are responsible for immediate release of calcium from the bone if the blood
calcium is too low.
* . . . protect the bone from chemicals in the blood which dissolve crystals (such as
pyrophosphate).
* . . . have receptors for hormones and factors that initiate bone remodeling.
Bone cell origins
This diagram summari'es the origins and fates of the bone cells. Mesenchymal refers
to cells which were deep within the embryo during early development2 some of them
remain in the bone marrow but do not form blood cells. The hematopoietic cells form
the li3uid part of the bone marrow, and some of them circulate with the blood.
Local regulators
4one cells produce molecules (usually
proteins) that communicate with other
cells. These molecules are called growth
factors and cyto+ines. They act on nearby
cells, and thus are considered local
regulators. These factors control cell
division (proliferation), differentiation, and
survival.
Growth factors
4one morphogenetic proteins (4MPs)5
4MPs are produced in the bone or bone
marrow. They bind to 4MP receptors that
are on mesenchymal stem cells within the
bone marrow. This causes the cells to
produce ,bfa -, which is a factor that
activates the ."! so proteins can be
made $$ a process +nown as gene
transcription. 1hen ,bfa - activates the
genes, the cells differentiate into mature
osteoblasts. 1ithout ,bfa -, the cells
would turn into fat cells instead6
7nsulin$li+e growth factors (7%8s)5 These
growth factors are produced by
osteoblastic cells in response to several
bone active hormones, such as
parathyroid hormone and estrogens, or
4MPs. 7%8s accumulate in the bone matri&
and are released during the process of
bone remodeling by osteoclasts. 7%8s
stimulate osteoblastic cell replication $$ in
other words, they cause the osteoblasts to
divide, forming new cells. They may also
induce differentiation.
Cytokines
7nterleu+in$- (79$-), interleu+in$: (79$:),
and tumor necrosis factor (T"8) family of
cyto+ines5 These factors are produced by
osteoblastic cells in response to systemic
hormones or other cyto+ines. 79$: can
cause5
* 4one marrow stem cells to differentiate
into pre$osteoclasts
* ,hanges in proliferation and
differentiation of osteoblasts
* 7nhibition of apoptosis of osteoblasts
!"#9 (!"#$ligand) is a cyto+ine that
stays on the surface of osteoblast$related
cells. The cells ma+e !"#9 in response
to systemic hormones (such as
-,;<dihydro&yvitamin .=) and cyto+ines
(such as 79$:). ,ell contact between
!"#9$e&pressing osteoblastic cells and
!"#$e&pressing osteoclast precursors
induces osteoclast development, as shown
in the animation in the osteoclast section.
Apoptosis
The mature bone is always remodeling5 the old bone is resorbed and replaced with
new bone. ! team of osteoblasts and osteoclasts move along the bone, dissolving
and rebuilding. 1hat happens to the cells when they have finished rebuilding an area
of bone> The osteoclasts and most of the osteoblasts undergo a process called
apoptosis, or cell suicide. They are not +illed. There is no lac+ of o&ygen or nutrients.
There are no to&ic materials. 7nstead, there are genes in the cell which can be
activated, causing the cell to disintegrate. These genes (of course) are carefully
regulated within the cell. The factors that regulate apoptosis are currently under
investigation. ?ome are related to estrogens, or to interleu+ins. Medications which
could modify apoptosis have the potential for treating or preventing osteoporosis.
Osteoporosis forum
U*X*L Complete Health Resource :: Sick! V3
OSTEOPOROSIS
DEFINITION
The wor !osteoporosis! literall" mea#s !porous $o#es%! Osteoporosis &pro#ou#ce OSS'
tee'o'puh'RO'sis( occurs whe# $o#es $e)i# to lose some of their esse#tial eleme#ts% The
most importa#t of these eleme#ts is calcium% O*er time+ $o#e mass ecreases% ,s a result+
$o#es lose their stre#)th+ $ecome fra)ile+ a# $reak easil"% -# e.treme cases+ e*e# a
s#ee/e or a sue# mo*eme#t ma" $e e#ou)h to $reak a $o#e%
DESCRIPTION
Osteoporosis is a serious health pro$lem% ,$out 01 millio# people i# the U#ite States
ha*e the co#itio#% -t is respo#si$le for a$out 2%3 millio# fractures &$roke# $o#es( each
"ear% The most commo# locatio#s where $reaks occur are the hip+ spi#e+ a# wrist% Hip
a# spi#e i#4uries are the most serious% The" ofte# re5uire hospitali/atio# a# ma4or
sur)er"% The" ma" also lea to other serious co#se5ue#ces+ i#clui#) perma#e#t
isa$ilit" a# eath%
Osteoporosis !ords to "no#
Alendronate:
, ru) use to treat osteoporosis i# wome# who ha*e passe throu)h me#opause%
Calcitonin:
, ru) use to treat osteoporosis i# wome# who ha*e passe throu)h me#opause%
Calcium:
,# esse#tial mi#eral with ma#" importa#t fu#ctio#s i# the $o"+ o#e of which is
i# the formatio# of $o#e%
Computed tomography (CT) scan:
, ia)#ostic tech#i5ue i# which a specific re)io# of the $o" is X'ra"e from
ma#" a#)les% , computer the# com$i#es the *arious X'ra" photo)raphs%
Computerized axial tomography (CAT) scan:
,#other #ame for a compute tomo)raph" &CT( sca#%
Densitometry:
, tech#i5ue for measuri#) the e#sit" of $o#e $" taki#) photo)raphs with low'
e#er)" X ra"s from a *ariet" of a#)les arou# the $o#e%
Estrogen:
, female hormo#e with ma#" fu#ctio#s i# the $o"+ o#e of which is to keep $o#es
stro#)%
Hormone replacement therapy (HRT):
, metho of treati#) osteoporosis $" )i*i#) suppleme#tar" oses of estro)e#
a#6or other female hormo#es%
Menopause:
The perio i# a woma#7s life whe# she stops me#struati#)%
rotein:
, t"pe of chemical compou# with ma#" esse#tial fu#ctio#s i# the $o"+ o#e of
which is to $uil $o#es%
Resorption:
The process $" which the eleme#ts of $o#e are remo*e from $o#e a# retur#e
to the $o"%
To u#ersta# osteoporosis+ it is helpful to u#ersta# how $o#es form% 8o#e is li*i#)
tissue that is co#sta#tl" re#ewe i# a two'sta)e process% The first sta)e is formatio#%
9uri#) formatio#+ #ew $o#e tissue is $uilt up from #utrie#ts prese#t i# the $loostream%
The seco# sta)e is resorptio#% -# this sta)e+ $o#e cells $reak ow#% The eleme#ts of
which are retur#e to the $loo a# other $o" fluis%
:or a$out the first thirt" "ears of life+ $o#e formatio# takes place faster tha# resorptio#%
8o#es )row to $e lar)er a# stro#)er uri#) this perio% ,fter mile a)e+ resorptio#
takes place faster a# $o#es $ecome smaller a# weaker%
Osteoporosis is a co#ti#uatio# of this process% The $ala#ce $etwee# resorptio# a#
formatio# $ecomes *er" o#e'sie% ,lmost #o #ew $o#e is forme+ $ut $o#e co#ti#ues to
$e remo*e% ;he# $o#es are mae smaller a# weaker $" this mecha#ism+ the process is
calle primar" osteoporosis%
Osteoporosis ca# also occur i# a#other wa"% Some ru)s a# iseases ca# i#crease the
rate at which resorptio# occurs% The e# result is the same: $o#es $ecome smaller a#
weaker% -# this case+ howe*er+ the process is calle seco#ar" osteoporosis%
Osteoporosis occurs most commo#l" i# oler people% -t affects #earl" half of all me# a#
wome# o*er the a)e of se*e#t"'fi*e% ;ome# are fi*e times more likel" tha# me# to
e*elop the co#itio#% The" ha*e smaller+ weaker $o#es to $e)i# with+ so resorptio# of
$o#e material i# wome#7s $oies has a )reater effect tha# i# me#7s $oies%
,#other importa#t factor i# osteoporosis is me#opause% <e#opause is the perio i# a
woma#7s life whe# she stops me#struati#)% 9uri#) this perio+ she also stops prouci#)
the hormo#e estro)e#% =stro)e# helps pre*e#t the resorptio# of $o#e% ,s le*els of
estro)e# fall i# a woma#7s $o"+ she is at )reater risk for osteoporosis%
CA$SES
,s outli#e+ osteoporosis is cause whe# the rate of $o#e resorptio# $ecomes )reater tha#
the rate of $o#e formatio#% This process is a #ormal part of a)i#)% There are certai#
factors+ howe*er+ that i#crease a perso#7s risk for osteoporosis% These factors i#clue:
!ender" ;ome# are more likel" to ha*e osteoporosis tha# me#% ;ome#
commo#l" lose 3> perce#t to 3> perce#t of their $o#e mass o*er their lifetimes%
<e# lose a$out 0> perce#t to 33 perce#t of their $o#e mass%
Race" Caucasia# a# ,sia# wome# are at somewhat hi)her risk for osteoporosis
tha# are ,frica# ,merica# a# Hispa#ic wome#%
#ody structure" -#i*iuals with smaller+ thi##er $o#es are at hi)her risk for
osteoporosis%
Early menopause" ;ome# who )o throu)h me#opause earlier start losi#) $o#e
mass earlier% =arl" me#opause ma" $e cause $" a #um$er of factors+ such as
hereit"+ sur)er"+ *i)orous e.ercise+ a#ore.ia &see a#ore.ia #er*osa e#tr"(+ a#
$ulimia &see $ulimia #er*osa e#tr"(%
$i%estyle" ,lcohol co#sumptio# a# to$acco use are thou)ht to i#crease risk for
osteoporosis% Lack of e.ercise ma" ha*e the same effect%
Diet" Two importa#t #utrie#ts #eee for $o#e formatio# are protei# a# calcium%
, iet low i# either of these #utrie#ts ma" lea to osteoporosis%
S%&PTO&S
Osteoporosis is sometimes calle the !sile#t isease%! The term reflects the fact that the
co#itio# usuall" has #o s"mptoms% ?eople ofte# o#7t k#ow the" ha*e the isorer u#til
the" $reak a $o#e uri#) some mi#or accie#t%
,s osteoporosis e*elops+ cha#)es i# $o" structure ma" occur% , perso# ma" actuall"
)row shorter% This cha#)e occurs whe# *erte$rae &$o#es i#
-llustratio# of osteoporosis $o#e matri.% &@ 2AAB% Reprouce $" permissio# of
Custom <eical Stock ?hoto
%(
the spi#e( eteriorate a# collapse% Loss of *erte$rae mass ca# also result i# the co#itio#
k#ow# as !owa)er7s hump! or !wiow7s hump%! This co#itio# is characteri/e $" the
hu#ch$acke appeara#ce ofte# see# i# oler wome#%
DIA'NOSIS
The o#l" wa" to ia)#ose osteoporosis with certai#t" is with X ra"s% Ori#ar" X'ra"
tech#i5ues+ like those use for chest X ra"s+ are usuall" #ot *er" helpful% The" o #ot
show $o#e loss u#til the isease has pro)resse a# e.te#si*e ama)e has occurre%
Compute tomo)raph" &CT( sca#s ma" $e more helpful% -# a CT sca#+ a specific re)io#
of the $o" is X'ra"e from ma#" a#)les% , computer the# com$i#es the *arious X'ra"
photo)raphs% CT sca#s are #ot the $est choice for ia)#osi#) osteoporosis+ howe*er+
$ecause the" re5uire relati*el" hi)h le*els of raiatio#% ,#other commo# #ame for a CT
sca# is a computeri/e a.ial tomo)raph" &C,T( sca#%
, $etter metho for ia)#osi#) osteoporosis is e#sitometr" &pro#ou#ce 9=C'si'TO<'
i'tree(% 9e#sitometr" is also a tech#i5ue for X'ra"i#) $o#es% Howe*er+ the amou#t of
raiatio# use is *er" low% The X ra"s are take# from iffere#t a#)les a# ca# show how
much $o#e has $ee# lost%
Some octors recomme# that people $e teste o# a re)ular $asis for $o#e loss% :or
wome#+ those tests shoul $e)i# after me#opause% :or me#+ the" shoul $e)i# after the
a)e of si.t"'fi*e% Such tests are importa#t si#ce there are selom other si)#s of
osteoporosis%
TREAT&ENT
Treatme#t epe#s o# the form of osteoporosis a patie#t has% -f a patie#t has seco#ar"
osteoporosis+ treatme#t is aime at curi#) the isease that has cause osteoporosis% -# the
case of primar" osteoporosis+ meicatio#s are use to a4ust the $ala#ce $etwee# $o#e
resorptio# a# $o#e formatio#% Treatme#t ma" also $e #ecessar" for $o#e fractures
resulti#) from osteoporosis% The most commo# treatme#t for such fractures is sur)er"%
Drugs
:or wome# who ha*e )o#e throu)h me#opause+ the first li#e of treatme#t ma" $e
hormo#e replaceme#t therap" &HRT(% -# hormo#e replaceme#t therap"+ a woma# is )i*e#
the estro)e# that her $o" #o lo#)er prouces o# its ow#% The estro)e# ca# $e )i*e#
orall" &$" mouth( or $" i#4ectio#% <a#" wome# choose HRT for other reaso#s as well% -t
helps ease the s"mptoms of me#opause% -t ca# also protect a)ai#st heart isease+ the
#um$er'o#e killer of wome# i# the U#ite States% HRT oes ha*e some harmful sie
effects+ howe*er% :or e.ample+ it ma" i#crease a woma#7s risk for $reast ca#cer &see
$reast ca#cer e#tr"(%
Other meicatio#s ca# $e use to treat osteoporosis% These meicatio#s reuce the rate of
$o#e resorptio# a#6or i#crease the rate of $o#e formatio#% The two most commo# ru)s
use for these purposes are ale#ro#ate a# calcito#i#% These ru)s ma" $e )i*e# $"
i#4ectio# or i# the form of #ose spra"s%
Surgery
-# a*a#ce sta)es of osteoporosis+ ma4or fractures are commo#% -# such cases+ sur)er"
ma" $e re5uire to repair the fracture% O#e of the most commo# proceures is hip
replaceme#t sur)er"% Hip replaceme#t sur)er" is use to repair a $roke# hip% The ori)i#al
hip is remo*e a# replace with a# artificial metal a#6or plastic hip% Hip replaceme#t
sur)er" is usuall" 5uite successful% ?atie#ts ca# ofte# retur#
-llustratio# showi#) atroph" of a hip $o#e% &@ 2AA3
?atrick <c9o##el
% Reprouce $" permissio# of
Custom <eical Stock ?hoto
%(
to a relati*el" #ormal life% Howe*er+ the sur)er" carries some serious risks% The eath rate
followi#) such sur)er" ma" $e 3 perce#t to 0> perce#t )reater tha# for others of the same
a)e )roup who ha*e #ot ha sur)er"%
Alternative Treatment
The primar" approach for most alter#ati*e practitio#ers is the same as it is i# traitio#al
meici#e% The )oal is to make sure that i#i*iuals recei*e the #utrie#ts the" #ee to
$uil stro#) $o#es i# their ail" iet% This mea#s a iet rich i# calcium a# protei#+
i#clui#) foos such as air" proucts+ ark')ree# leaf" *e)eta$les+ sari#es+ salmo#+
a# almo#s% Cutritio#al suppleme#ts such as *itami# 9+ calcium+ a# ma)#esium ma"
also $e recomme#e%
Her$alists a# Chi#ese meici#e practitio#ers $elie*e that certai# her$s ca# slow the rate
of $o#e loss% ,mo#) the proucts the" recomme# are horsetail+ oat straw+ alfalfa+
licorice+ marsh mallow+ "ellow ock+ a# ,sia# )i#se#)% Homeopathic practitio#ers
recomme# mi#erals such as Calcarea carbonica or silica% , su$stitute for HRT is to
o$tai# hormo#es from #atural sources+ such as so"$ea#s a# wil "ams%
PRO'NOSIS
There is #o cure for osteoporosis% Howe*er+ it ca# $e co#trolle 5uite well o#ce it has
$ee# ia)#ose% <eicatio#s+ #utritio#al suppleme#ts+ a# a iet rich i# calcium a#
protei# ca# help slow the pro)ress of the isorer%
PRE(ENTION
To a si)#ifica#t e.te#t+ osteoporosis is a pre*e#ta$le isease% ?eople ca# take a #um$er of
steps $e)i##i#) earl" i# life to $uil stro#) $o#es% 8" co#ti#ui#) those practices as the"
)row oler+ the" ca# reuce the rate of $o#e loss% Some of these steps i#clue:
Det calcium i# foos% :oos rich i# calcium i#clue milk+ cheese+ "o)urt+ a#
other air" prouctsE )ree# leaf" *e)eta$lesE tofuE shellfishE 8ra/il #utsE sari#esE
a# almo#s%
Take calcium suppleme#ts% , perso# ca# $e certai# of )etti#) e#ou)h calcium $"
taki#) suppleme#ts i# the form of pills%
Det e#ou)h *itami# 9% Vitami# 9 helps the $o" a$sor$ calcium% The easiest wa"
to )et *itami# 9 is from su#shi#e% , fiftee#'mi#ute walk each a" usuall"
pro*ies all the *itami# 9 o#e #ees% :oos rich i# *itami# 9 i#clue li*er+ fish
oil+ a# milk fortifie with *itami# 9%
,*oi or limit smoki#) a# the use of alcohol% 8oth smoki#) a# alcohol use
seem to i#crease the rate of $o#e loss% 8" limiti#) $oth acti*ities+ the risk of
osteoporosis ma" $e reuce%
=.ercise% Re)ular e.ercise $uils stro#) $o#es% The forms of e.ercise likel" to $e
most effecti*e i#clue aero$ics+ a#ci#)+ 4o))i#)+ stair clim$i#)+ te##is+ walki#)+
a# lifti#) wei)hts% =.perts recomme# twe#t" to thirt" mi#utes of e.ercise three
to four times a week%
.ate, 4M. inde&, t$score and '$score are displayed in the upper right area of the report @!A.
The results are also graphed against age in the mid section @4A.
8or patients with more than one Osteo%ram test, multiple set of numbers show in @!A and
accordingly multiple connected dots show in the graph @4A.
The graph plots t$scores vs age, hence straight lines @,A reflect the grid of t$score. 1ith proper
curving, the curved lines @.A become the grid of '$score, and the same dot can be read as '$
score as well.
The 1orld )ealth Organi'ation (1)O) guidelines for interpreting t$score results are displayed at
the bottom @/A.
!ccording to the 1)O criteria5 normal patients have high t$scores, more than $-.B (green area
in graph)2 osteoporosis patients have low t$scores, less than $;.< (orange area in graph)2 and
patients in the mid range would classify as having osteopenia (yellow area in graph).
! summary of the patient(s condition is highlighted in blue @8A.

Terapi Sulih Hormon Tidak Seratus Persen Aman
AKHIRNYA, perempuan yang terombang-
ambing dalam keraguan apakah ia perlu
mendapatkan terapi sulih hormon (hormon
replacement therapy/HRT, mendapat
kepastian! Institut Nasional "antung, #aru-
paru, dan $arah di Amerika %erikat (A%
mengumumkan, %elasa (&/', bah(a
perempuan sehat yang men)alani HRT
dengan kombinasi hormon estrogen dan
progestin setelah menopause, bertambah
risikonya terkena kanker payudara, stroke,
penggumpalan di darah, dan penyakit
)antung!
#erempuan dian)urkan tidak memulai atau
melan)utkan terapi tersebut untuk
men*egah penyakit )antung,+ kata $r "a*,ues Rossou( dari Institut Nasional "antung, #aru-
paru, dan $arah, yang membantu penelitian epidemiologi terhadap perempuan yang
men)alani HRT di A%, seperti dikutip kantor berita Reuters!
HRT diberikan kepada para perempuan yang telah memasuki -ase menopause untuk
membantu men*egah terkena penyakit )antung dan osteoporosis! .ase menopause adalah
tahapan di mana seorang perempuan berhenti mengalami menstruasi, dan pada saat itu,
produksi hormon estrogennya )uga menurun se*ara drastis! #enurunan estrogen itulah yang
memun*ulkan ge)ala-ge)ala menopause!
/e)ala-ge)ala menopause sangat ber0ariasi dari satu perempuan ke perempuan lain, tetapi
kebanyakan perempuan mengalami yang disebut hot flashes atau hut flushing yaitu sensasi
tiba-tiba merasa panas di bagian atas tubuh yang bisa berlangsung satu menit atau lebih!
Hal ini )uga bisa ter)adi pada malam hari dan diikuti rasa dingin tiba-tiba, seperti yang ter)adi
pada saat demam! Yang )uga biasa mun*ul adalah rasa nyeri di persendian, sulit tidur
(insomnia, rasa tertekan tanpa sebab, -luktuasi suasana hati, rasa sakit saat berhubungan
intim, 0agina yang kering, sakit kepala, rasa lelah, dan banyak lagi!
#erubahan yang lebih nyata adalah menyusutnya -ungsi sistem reproduksi, berkurangnya
kekuatan otot, perubahan pada bentuk tubuh men)adi berbentuk apel (lemak di daerah
pinggang atau berbentuk pir (perlemakan di daerah pinggul dan paha, payudara tidak lagi
ken*ang, perubahan pada kulit, osteoporosis (pengeroposan tulang, meningkatnya risiko
penyakit )antung!
***
#1N12ITIAN yang dipublikasi di dalam Journal of the American Medical Association (JAMA)
3olume 455 No 6, 7' "uli 4884 (situs9 ama!ama"assn!org men)adi pukulan kedua untuk
terapi HRT! #ara dokter membuat laporan -inal yang mengon-irmasi bah(a terapi yang
mengombinasikan estrogen dan progestin tidak melindungi perempuan dari penyakit )antung
setelah menopause!
Ka)ian terhadap 7:!:88 perempuan di A% menun)ukkan bah(a terapi HRT menurunkan
risiko terkena pengeroposan tulang dan kanker usus, tetapi menaikkan risiko stroke ;7
kompas/%utta $harmasaputra
persen, serangan )antung 4& persen, dan kanker payudara 4: persen!
<enurut %u=anne .let*her <$ <%* dan /raham A >lodit= <$ $r#H dalam #ditorial di
JAMA, diperkirakan 65 persen perempuan yang memasuki tahap postmenopause di A%
menggunakan HRT! #ada tahun 4888, dokter menulis ;: )uta resep #remarin (gabungan
estrogen-estrogen, sehingga men)adi obat kedua terbesar yang pernah diresepkan di A%
dengan nilai pen)ualan lebih dari satu milyar dollar A%! #ada tahun yang sama, 44,6 )uta
resep dibuat untuk #rempro (gabungan antara estrogen-estrogen dan asam-
medroksiprogesteron! .ood and $rug Administration, A%, menyetu)ui HRT dengan indikasi
mengurangi ge)ala menopause, mengurangi risiko osteoporosis, dan men*egah penyakit
kronis seperti penyakit )antung!
%emula, HRT hanya dengan menggunakan hormon estrogen! Naiknya risiko kanker
endometrium menyebabkan HRT mengombinasikan estrogen dengan progestin untuk
perempuan yang masih memiliki rahim lengkap! %e)ak pertengahan tahun 7&58-an
penggunaan kombinasi estrogen/progestin telah meningkat se*ara mantap!
$i antara banyaknya penelitian mengenai risiko dan man-aat HRT pada perempuan sehat
yang mengalami menopause, hasilnya belum memberi kepastian!
2alu, ?omen@s Health Initiati0e (?HI membuat sebuah ka)ian pan)ang (diren*anakan
selama 5,A tahun melibatkan 7:!:85 perempuan menopause berusia A8-'& tahun dengan
rahim yang lengkap yang direkrut oleh ;8 klinik di berbagai tempat di A% antara tahun 7&&6-
7&&5!
Hasil utama penelitian yang baru ber)alan selama A,4 tahun dihentikan lebih dini dari
ren*ana semula karena hasil menun)ukkan risiko yang lebih tinggi dibandingkan
man-aatnya!
<enurut laporan ?HI dalam JAMA, hasil utama menun)ukkan meningkatnya kanker
payudara in0asi- dan penyakit )antung, ditambah stroke, emboli paru, kanker endometrial!
Karena hasil tersebut, demikian laporan ?HI, de(an pemantau data dan keselamatan
merekomendasi per*obaan pemberian estrogen/progestin 0ersus plasebo (tablet kosong
tanpa pemakai mengetahui untuk mendapat komentar obyekti- pemakai!
Hasil-hasil yang merugikan ini mun*ul dalam kurun satu sampai dua tahun setelah terapi,
tetapi risiko kanker payudara tidak mun*ul sampai tiga tahun penggunaan terapi kombinasi
hormon tersebut!
Bila diukur berdasarkan risiko absolut, demikian editorial JAMA, angkanya ke*il sa)a untuk
setiap perempuan! $ari setiap 78!888 perempuan yang men)alani terapi kombinasi, akan
ada tu)uh ke)adian penyakit )antung koroner, delapan ke)adian kanker payudara in0asi-,
delapan ke)adian stroke, delapan ke)adian emboli paru-paru, tetapi ter)adi pengurangan
enam ke)adian kanker kolorektal dan lima patah panggul! <eskipun demikian, bila dihitung
semua yang terlibat dalam penelitian A,4 tahun ini adalah 788 ke)adian per 78!888
perempuan (satu dari 788 perempuan! Angka risiko ini termasuk ke*il, tetapi penelitian
menun)ukkan risiko dari terapi ini meningkat dengan ber)alannya (aktu!
Hal penting lainnya, tu)uan utama terapi sulih hormon dalam )angka pan)ang adalah untuk
men)aga kesehatan dan men*egah penyakit! Hasil penelitian ini menun)ukkan bukti kuat
bah(a hal yang sebaliknya ter)adi untuk aspek penting kesehatan perempuan, bahkan
meskipun risiko absolutnya ke*il!
+Berdasarkan hasil riset ini, kami merekomendasikan para dokter berhenti meresepkan
pengobatan kombinasi hormon ini untuk )angka pan)ang,+ demikian disebutkan dalam
editorial JAMA!
Rossou( dalam )umpa pers %elasa lalu mengatakan, mungkin sa)a aman men)alani terapi
sulih hormon untuk )angka pendek! +Tetapi, sangat sulit untuk menetapkan apa yang
dimaksud dengan periode yang aman,+ katanya!
%ementara ini, penelitian terapi sulih hormon dengan menggunakan hanya hormon estrogen
pada perempuan yang telah diangkat rahimnya masih terus berlan)ut!
***
<1NC#AD%1 sebenarnya hanyalah sebuah tahap transisi yang harus dilalui setiap
perempuan! <enurut "ohn R 2ee <$ dan 3irginia Hopkins dalam $hat The %octor May &ot
Tell 'ou A(out Menopause (7&&&, dengan )umlah 68 )uta perempuan di A% sa)a yang
mengalami menopause dan 48 )uta lainnya akan memasuki periode menopause, tidak
mengherankan bila perusahaan -armasi membentuk *itra bah(a menopause adalah sebuah
penyakit! $engan terbentuknya *itra tersebut, maka perempuan memerlukan +obat+ ketika
memasuki -ase ini!
Banyak perempuan merasa takut men*apai masa menopause yang biasanya ter)adi pada
usia ;5-A4 tahun! %alah satu alasan mengapa banyak perempuan enggan membi*arakan
mengenai -ase menopause mereka karena ada anggapan umum bah(a ini adalah pintu
yang harus dilalui menu)u usia tua!
<enurut "ohn R 2ee <$ dan "esse Henley <$ dalam $hat 'ou May &ot Tell 'ou A(out
Premenopause, sikap negati- seperti ini akan memperburuk ge)ala pramenopause yang
disebabkan oleh emosi! %ikap ini barangkali memang bisa menghinggapi perempuan yang
belum memiliki anak dan berharap apakah mereka bisa mendapatkannya sebelum )am
biologis mereka mati!
<enurut 2ee dan Henley, hal ini tidak lain karena se*ara budaya, perempuan dilatih untuk
meyakini bah(a nilai mereka terletak pada kemampuan mereka untuk bereproduksi dan
mendukung tanpa syarat kepada laki-laki! #erempuan )uga selalu dia)arkan untuk
memberikan seluruh *intanya tanpa syarat untuk anak-anaknya!
+Hal ini memang merupakan salah satu *iri -eminin, tetapi hal ini sangat sepihak!
#erempuan yang hanya mengembangkan *iri ini tanpa membangun kesadaran tentang
dirinya, akan ketakutan menghadapi ketuaan! Ketika anak-anak meninggalkan rumah
(setelah de(asa, payudaranya mengendur, kulitnya berkeriput, apa lagi yang dimilikinyaE+
tulis 2ee dan Henley!
Keduanya mengingatkan, tidak mengherankan bila perempuan dengan sikap seperti ini
melalui proses men)adi manusia yang lebih indi0idual dan bebas bisa men)adi sesuatu yang
menakutkan!
#adahal, begitu seorang perempuan melalui -ase menopause, ia adalah seorang manusia
baru dan dia memiliki potensi untuk menemukan bagian paling kaya dalam hidupnya!
%eorang perempuan yang telah melalui satu atau dua tahun masa a(al menopause-nya
akan memandang lima tahun pertama hidupnya dengan bi)aksana dan menggabungkannya
dengan rasa kebebasan! +<enopause pernah suatu masa disebut sebagai @usia berbahaya@
karena banyak perempuan mulai menyatakan pendapatnya pada -ase tersebut! Yang
diperlukan oleh dunia adalah perempuan yang berani mengatakan isi pikirannya,+ tambah
2ee dan Henley!
Berbagai ge)ala tidak mengenakkan yang menyertai manopause seperti semburan panas,
0agina yang mengering, dan berubah-ubahnya suasana hati, menurut 2ee, umumnya
mun*ul di negara-negara Barat, dan )arang ter)adi di negara-negara Timur atau di negara-
negara berkembang!
$i negara-negara non-Barat, perempuan yang memasuki masa menopause )ustru
dipandang sebagai perempuan yang bi)aksana karena banyaknya pengalaman yang telah
dilaluinya! <ereka men)adi tempat orang men*ari nasihat di komunitasnya! <ereka kini
terbebas dari masa subur, dan tiba (aktunya untuk memberi (aktu bagi penggalian potensi
diri!
#enyebab perbedaan ini menurut 2ee dan Hopkins terletak pada makanan yang tidak
lengkap gi=i, gaya hidup yang tidak sehat, polusi lingkungan, tingkah laku budaya,
penggunaan hormon sintetis, dan iklan!
Tentang yang terakhir ini, perempuan harus bisa bersikap kritis dan mengetahui keadaan
dirinya sendiri dengan baik! Apakah kita memang benar-benar membutuhkan terapi sulih
hormon, apakah kita telah mendapatkan nasihat yang benar-benar obyekti- dan
mempertimbangkan keuntungan kita sebagai manusia, dan bukan karena ada pengaruh
perusahaan-perusahaan -armasi raksasa yang melihat keuntungan di balik pen)ualan obat-
obat terapi sulih hormonE Bila Anda ragu, )angan segan untuk meminta opini dari seorang
ahli lainnya, demi kualitas hidup kita sendiri!
***
A$A banyak *ara untuk tetap mendapatkan hidup yang tetap berkualitas setelah memasuki
masa menopause! 1laine <agee <#H R$ dalam #at $ell for a Healthy Menopause
menyebutkan antara lain )enis sayuran dan buah yang tepat akan membantu mengatasi
masalah pada masa pramenopause pada usia 68-an sampai ;A tahun, perimenopause atau
satu-dua tahun men)elang dan setelah menopause, dan saat menopause!
Tanaman yang mengandung -itoestrogen atau estrogen yang berasal dari tumbuhan akan
membantu +menangkap+ estrogen yang berlebihan saat -ase premanopause dan membantu
mengurangi risiko terkena kanker payudara yang disebabkan oleh tingginya hormon
estrogen dan rendahnya hormon progesteron, sementara pada masa perimenopause dan
pas*amenopause ketika hormon estrogen se*ara drastis berkurang produksinya,
-itoestrogen akan berlaku seperti estrogen meskipun dayanya tidak sebesar estrogen!
<akanan yang banyak mengandung -itoestrogen (terdiri dari iso-la0onoid dan lignan dan
)uga boron-yang membantu meningkatkan kadar estrogen-adalah ka*ang kedelai yang bisa
dikonsumsi dalam bentuk tempe, tahu (pilih yang tanpa penga(et atau boraks, atau susu
kedelai! %ayuran ber(arna seperti brokoli dan (ortel mengandung -itoestrogen dan boron!
Apel, kol, kembang kol, timun, ba(ang putih, ba(ang merah, ubi merah, adalah )enis-)enis
tanaman yang mengandung boron dan -itoestrogen tinggi! Namun, pada dasarnya semua
sayuran dan buah-buahan adalah sumber nutrisi yang menyehatkan! (NINDK <#
Figure 15 ?tructure of, functional domains of, and described polymorphisms in the
human estrogen receptor gene. ,oding e&ons (/) are indicated with bo&es. T!8, transcriptional
activating function.
Figure 25 .istribution of (T!) n repeat alleles in the human estrogen receptor gene in different
ethnic groups. Top5 Ma*or studies in 7talian (=C) and .utch (<-) ,aucasian populations. 4ottom5
Ma*or studies in Dapanese (E<) and ,hinese (--F) !sian populations.
Figure 35 ?tructure of, functional domains of, and described polymorphisms in the human estrogen
receptor G gene. ,oding e&ons (/) are indicated with bo&es. T!8, transcriptional activating function2
HT, untranslated region
Ho& Estrogen 'or(s
Taki#) estro)e# after me#opause
reuces a woma#7s risk of heart
isease a# osteoporosis% 8ut raises
the risk of uteri#e ca#cer a# possi$l"
$reast ca#cer%
The ideal designer
estrogen
The #ew esi)#er
estro)e#s ca# impro*e the
outlook for osteoporosis
while possi$l" loweri#)
the risk for $reast ca#cer%
-# the future+ octors
coul prescri$e estro)e#
custom' esi)#e for each
woma#7s risk profile% The
ieal woul o the
followi#):
Robin Marantz Henig is a Washington-based medical writer whose books include