arasrulyofili osteogenezi

klinikuri praqtikis erovnuli rekomendacia

(gaidlaini)

2

klinikuri praqtikis erovnuli rekomendacia (gaidlaini)

`arasrulyofili osteogenezi~ miRebulia klinikuri praqtikis

erovnuli rekomendaciebis (gaidlainebi) da daavadebaTa marTvis

saxelmwifo standartebis (protokolebi) SemuSavebis, Sefasebis

da danergvis erovnuli sabWos 2008 wlis 5 noembris #1 sxdomaze

da damtkicebulia saqarTvelos Sromis, janmrTelobisa da

socialuri dacvis ministris 2008 wlis 18 dekembris # 279/o

brZanebiT.

3

arasrulyofili osteogenezi

1. daavadebis definicia, sinonimebi, klasifikacia da terminologia

arasrulyofili osteogenezi (osteogenesis imperfecta - OI) SemaerTebeli

qsovilis memkvidreobiTi daavadebaa, romlis klinikur suraTSi wamyvania

xSiri motexilobebi, romelTac, rogorc wesi, raime cxadi uSualo mizezi

ar aqvs da arc gareSe Zalis moqmedebiT warmoebs (ris gamoc daavadebul

bavSvebs SuSis bavSvebs uwodeben). Zvlebis xSiri motexiloba da am

daavadebisaTvis damaxasiaTebeli araidentificirebuli meqanizmebi, iwvevs

sayrden-mamoZravebeli sistemis deformaciebs da funqciur SezRudvebs.

sazogadod arasrulyofili osteogenezi gamoxatul invalidobasTan aris

dakavSirebuli. igi iSviaT daavadebaTa ricxvs miekuTvneba.

jandacvis saerTaSoriso organizaciis mier arasrulyofili osteogenezi

erT-erT umZimes daavadebad aris miCneuli. daavadebis naadrevi diagnostikis

da efeqturi mkurnalobis mizniT aucilebelia saTanado diagnostikuri

kompleqsuri RonisZiebebis Catareba, gansakuTrebiT mosaxleobis im

jgufebSi, romlebic “risk-kontigentad” iTvlebian. umravles SemTxvevaSi

daavadeba dakavSirebulia Sromis da sakuTari Tavis movlis uunarobasTan.

am mZime daavadebis gavlena bavSvis organizmze, sicocxlis xarisxze da mis

sulier komfortze katastrofulia, amasTanave es gavlena ar Semoifargleba

mxolod avadmyofiT, igi vrceldeba avadmyofis ojaxze da mTlianad

sazogadoebazec.

literaturaSi es daavadeba cnobili iyo sxvadasxva saxelwodebiT:

- Tandayolili raqiti;

- fsevdoraqiti;

- muclad yofnis periodis raqiti (Lusitan); - Tandayolili osteomalacia (Caniggia,Ekman); - guves sindromi ( Hoeve); - dispalasia periostalis (Porax, Durante); - aplasia periostalis (Muller); - aplasia ossea microplastica (Reсklinghausen); - osteogenesis congenita (Kundrat); - osteomalacia congenita (Jurgens); - dausrulebeli osteogenezi;

- arasruli osteogenezi.

dReisaTvis es daavadeba warmoadgens arasrulyofil osteogenezs, romelic

sazogadoebaSi cnobilia ZiriTadad `SuSis bavSvebis~ saxeliT.

1906 wels luzerma arasrulyofili osteogenezis ori forma gamoyo:

Tandayolili - osteogenesis imperfecta congenita da mogvianebiTi - osteogenesis imperfecta tarda - formebi. es klasifikacia arsebobda mravali aTwleulis

ganmavlobaSi, romelic efuZneboda pacientis pirveli motexilobis

ganviTarebis asaks.

1979 wels avstralielma genetikosma prof. David Sillence-ma da Tanaavtorebma

es klasikuri dayofa Secvales axali klasifikaciiT, romelic 4 tips

moicavs. es klasifikacia romelic ukve orjer gadamuSavda (Sillence,1981; Sillence da Tanaavt. 1984), efuZneba genetikur tips, motexilobaTa sixSires,

4

sklerebis fers, kbilebis mdgomareobas da klinikuri ganviTarebis

prognozs.

bolo dros aRweres kidev arasrulyofili osteogenezisO(OI-s) sami tipi V,

VI daVII.

klinikuri da genetikuri gamovlinebis mxriv variaciebis mravalferovnebis

gamo, zogierT SemTxvevaSi, romelime tipisadmi zusti mikuTvneba ver

xerxdeba.

Cven vixelmZRvaneleT Tanamedrove klasifikaciiT Sillence-s mixedviT:

5

2. epidemiologia

Harmut Stoss-is monacemebiT yovel 100 000 mosaxleze daaxloebiT 4-7 SemTxveva

modis.

Sillence-is mixedviT sxvadasxva tipis arasrulyofili osteogeneziT

daavadebulTa sixSire cvalebadobs: ase - pirveli tipisaTvis 1\30 000-ze,

maSin rodesac meore tipis SemTxvevebi 1\62 000. dReisaTvis mesame da meoTxe

tipebis arasrulyofili osteogeneziT daavadebulTa zusti sixSire

ucnobia.

H.W. Lehman –is da M. Herbold-is monacemebiT yovel 10 000 mosaxleze erTi

SemTxveva modis. vinaidan arasrulyofili osteogenezis msubuqi formebi

xSirad cxovrebis gviandel etapze diagnostirdeba an saerTodac ver

dgindeba, realuri cifri kidev ufro maRalia.

zogierTi avtoris monacemebiT es daavadeba mamrobiTi sqesis

warmomadgemlebSi ufro xSiria, vidre mdedrobiTis (Friant, В.Чаклин). magram, mecnierTa didi nawili miuTiTebs, rom daavadebis ganviTareba ar aris

damokidebuli sqesze.

aSS registrirebulia 50 000 daavadebuli, germaniaSi ki – 5000-mde.

arasrulyofili osteogeneziT daavadebulTa daxmarebis asociacias `SuSis

bavSvebi~, registrirebuli yavs 70-mde daavadebuli, romelTa 90% q.

Tbilisis mosaxlea. samwuxarod saqarTvelos masStabiT sxva statistikuri

monacemebi ar arsebobs.

3. etiopaTogenezi

arasrulyofili osteogenezi ganpirobebulia I tipis kolagenis

masinTezirebeli 2 genidan erT-erTis mutaciiT, romlis damemkvidreba

xdeba rogorc autosomur–dominanturi, aseve autosomur-recesiuli

meqanizmebiT, an spontanur mutacias aqvs adgili. radgan am daavadebisaTvis

damaxasiaTebelia defeqturi kolagenis biosinTezi, amitom am bavSvebSi

osteoblastebi warmoqmnian ufro naklebi raodenobiT ujredebs vidre es

saWiroa Zvlovani qsovilis formirebisaTvis. amgvarad, Bbalansi Zvlis

Sewovasa da formirebas Soris mimarTulia Zvlis rezorbciisaken.

daavadebas safuZvlad udevs I tipis kolagenis masinTezirebeli ori genidan

erT-erTis autosomur-dominanturi mutacia. aRwerilia daaxloebiT asi

gansxvavebuli mutacia. SemTxvevaTa umravlesobaSi adgili aqvs fuZeTa

bunebrivi Tanmimdevrobis cvlilebas wertilovani mutaciis saxiT, Tumca ki,

zogjer delecia aRiniSneba (Robert Lindsay 2002).

arasrulyofili osteogenezis genetika da I tipis kolagenis bioqimiuri

anomaliebi, romlebic dakavSirebulni arian motexilobebis riskTan,

TandaTan ufro metad gasagebi xdeba, Tumca daavadebis metaboluri Sedegebi

ConCxze, iseve rogorc motexilobis ganviTarebis riski jer kidev cudadaa

Seswavlili, bavSvevSi ConCxis homeostazis Sefasebis sirTulis gamo.

mutaciis Sedegi damokidebulia aminomJavebis cvlilebebis saxeze. Secvlili

aminomJavebis ricxvsa da molekulaSi cvlilebebis lokalizaciaze. Tu

mutaciis Sedegad geni wakiTxvas aRar eqvemdebareba, anda Sesabamisi alfa-

jaWvi imdenad icvleba, rom spiralis ageba ukve SeuZlebeli xdeba, maSin

vRebulobT nulovan alels. klinikurad ki daavdeba msubuqad mimdinareobs.

6

I tipis kolageni raodenobrivad naxevrad Tu aris Semcirebuli, magram

funqciurad intaqturi cilaa da Tu spiralSi mainc xdeba defeqturi alfa-

jaWvis CarTva, daavadeba vlindeba msubuqidan letalur formamde.

I tipis arasrulyofili osteogenezis dros kolageni normaluria, magram

normaluri raodenobis mxolod 50% sinTezirdeba, maSin rodesac II, III da

IV tipis SemTxvevaSi sinTezirebuli kolageni struqturulad

aranormaluria da molekuluri defeqti aqvs (2, 10 sarw .II done).

bolo dros aRmoCenil V da VI tipis arasrulyofili osteogenezis

SemTxvevaSi ar aqvs adgili im genebis mutacias, romlebic akodireben

pirveli tipis kolagens. es sakiTxi, rogorc sxva mravali am daavdebis

Sesaxeb, jer kidev Semdgom kvlevebs saWiroebs.

rogorc Sedegi defeqturi kolagenis biosinTezisa, osteoblastebi

arasrulyofili osteogenezis mqone bavSvebSi warmoqmnian ufro naklebi

raodenobis Zvals vidre saWiroa. balansi Zvlis gawovasa da formirebas

Soris, romelic normalur bavSvebSi mimarTulia Zvlis gasqelebisaken da

trabekulebis ganmtkicebisaken, daavadebis SemTxvevaSi mimarTulia Zvlis

rezorbciisaken.

arasrulyofili osteogenezis dros adgili aqvs defeqturi kolagenis

biosinTezs, am bavSvebSi osteoblastebi warmoqmnian ufro naklebi

raodenobiT ujredebs vidre es saWiroa Zvlovani qsovilis formirebisaTvis.

amgvarad, Bbalansi Zvlis Sewovasa da formirebas Soris, romelic janmrTel

bavSvebSi mimarTulia Zvlis gasqelebisa da trabekulebis ganmtkicebisaken,

daavadebis SemTxvevaSi mimarTulia Zvlis rezorbciisaken. Txeli pirveladi

trabekulebi scildebian erTmaneTs kolagenis defeqtis gamo, isini agreTve

midrekilni arian mikrodazianebebisaken, es ukanaskneli remodelirebis

samizneebia, rac iwvevs pirveladi trabekulebis eliminaciasa da Zvlis

dasustebas. amgvarad, arasrulyofili osteogeneziT daavadebul bavSvebs

aqvT patara Txeli Zvlebi, mcire raodenobis trabekulebiT, Txeli

kortikaluri SriT da remodelirebis maRali tempiT, rasac mivyavarT

motexilobebisa da deformaciebis ganviTarebamde.

Zvlovani matriqsis arasrulfasovneba da xangrZlivi hipodinamia iwvevs

osteoporozs, romelic droTa ganmavlobaSi ufro Rrmavdeba da amwvavebs

klinikur mimdinareobas.

4. klinikuri simptomatika

arasrulyofili osteogenezis klinikuri suraTi metad variabeluria da

gansxvavdeba tipebis mixedviT. ganmeorebadi da mravlobiTi motexilobebi,

romelTac sul mciredi travmac ki iwvevs, am daavadebis damaxasiaTebeli

niSania. gamovlinebis speqtri meryeobs nayofis saSvilosnosSida

sikvdilidan minimalur klinikur niSnebamde, romelTac daavadebas verc

vuwodebT. Zalin mZime SemTxvevebSi, rogoricaa am daavadebis meore tipi,

mravlobiTi motexilobebi viTardeba ukve saSvilosnos SigniT.

arasrulyofili osteogenezis es tipi letaluri formaa.

pirveli tipi SesaZloa imdenad msubuqi iyos, rom verc ki moxdes daavadebis

diagnostika. mesame da meoTxe tipebis klinikuri suraTis gamovlinebis

simZime pirvel da meore tipebs Sorisaa.

7

daavadebis sami klasikuri simptomia: susti da advilad msxvrevadi Zvlebi,

smenis TandaTanobiTi dakargva da Tvalis skleris cisferi feri (`lurji

sklerebi~). gasaTvaliswinebelia, rom yvela pacients SesaZloa ar

aReniSnebodes samive simptomi erTad, magram Zvlebis sisuste yvelasaTvis

damaxasiaTebelia.

umravles SemTxvevaSi damaxasiaTebelia motexilobis dros mcire tkivili,

amitom motexiloba SeiZleba SeumCnevelic darCes. yvelaze xSirad xdeba

qvemo kidurebis motexilobebi. motexili Zvlebis konsolidacia xdeba ufro

swrafad, vidre janmrTel ZvalSi (Виноградова). М. Обакевич-isa da В.Н. Блохин-is monacemebiT ki Zvlebis konsolidacia gvian vadebSi xdeba. sxva mecnierebi

ki miuTiTeben, rom motexili Zvlebis Sezrda normalur vadebSi xdeba.

motexili Zvlebis konsolidacia normalurad mimdinareobs da korZi

normalurad gamoiyureba, magram gardaqmna Camoyalibebul firfitovan Zvlad

ar xdeba, ris gamoc lulovani Zvlis xelaxali motexilobebis ganviTarebis

didi albaTobaa. zogjer motexiloba ganikurneba hiperplaziuri korZis

warmoqmniT. sazogadod, rac ufro adre iwyeba motexilobebi, miT ufro

mZimed mimdinareobs daavadeba.

motexilobaTa sixSire sxvadasxvaa da meryeobs erTidan aseulebamde. am

daavadebis dros icvleba ara mxolod Zvlovani qsovili aramed yvela saxis

SemaerTebeli qsovili met-naklebad. motexilobebis garda am

paTologiisaTvis damaxasiaTebelia:

arasrulyofili osteogenezis klinikuri niSnebi

• xSiri motexilobebi (minimaluri travmisas);

• zemo da qvemo kidurebis, aseve xerxemlis deformacia

(skoliozi an kifozi);

• Tavis qalas deformacia;

• samkuTxa saxe;

• zrdaSi CamorCena;

• saxsrebis iogovani aparatis sisuste;

• Cveuli amovardnilobebi;

• kanqveSa sisxlCaqcevebi;

• cisferi sklerebi;

• smenis daqveiTeba da dakargva;

• kbilebis deformacia da cveTa;

• gulis ukmarisoba;

• guneba-ganwyobilebis labiloba;

• gaZlierebuli daRliloba;

• oflianoba;

• SeiZleba gamoiwvios invalidoba, yavarjnebis an invalidis

savarZlis gamoyeneba.

8

xazi unda gaesvas im garemoebas, rom yvela simptomis gamovlena ar aris

aucilebeli. OI-is axasiaTebs individualuri gamovlineba. mraval adamianSi

OI gamovlindeba mxolod ramodenime simptomiT.

OI –s pirveladi diagnostika /jandacvis pirveladi rgolis med-personalisTvis/

klinikuri

niSnebi

specialistTan diagnozis

dasazusteblad (jandacvis

meoradi rgoli - stacionari)

genetikuri ganwyoba anamnezSi,

OI-s arseboba

mrav.

motexil

cisferi

sklera

zrdaSi

CamorCena

deformaci

ebi

OI –s saeWvo diagnozis arseboba

rentgenologiuri

kvleva

laboratoriuli

kvlva

Cveuli

amovardni

lobebi

smenis

daqveiTeba

an

dakargva

gulis

ukmarisoba

oflianoba

kbilebis

deformacia

da cveTa

saxsrebis

iogovani

aparatis

sisuste

Cveuli

amovardnil

obebi

dakvirveba klinikur

mimdinareobaze

genetikosi

pediatri

travmatologi

orTopedi

endokrinologi

kardiologi

reabilitologi

otolaringologi

9

daavadebis Tanmxlebi garTulebebi SeiZleba iyos:

otologiuri garTulebebi:

daavadebulTa daaxloebiT naxevars smenis daqveiTeba aReniSneba. I tipis dros smenis daqveiTeba 10-20 wlis asakidan iwyeba. smenaClungobis mizezi

metwilad sasmeni Zvlebis, xSirad uzangis deformacia, motexiloba, an

fiqsaciaa, rac otosklerozisTvis aris damaxasiaTebeli. arasrulyofili

osteogenezis dros Zvlovani lokokinis TandaTanobiT atrofiasac aqvs

xolme adgili.

II da III tipis arasrulyofili osteogenezisas smenis daqveiTebis sixSire

dadgenili ar aris, IV tipis dros ki smenaClungoba pacientTa 30%-Si

aRiniSneba da ZiriTadad I tipisTvis damaxasiaTebeli darRvevebiT vlindeba.

histologiuri gamokvlevebiT, arasrulyofili osteogenezis dros smenis

aparatis Zvlovani struqturis arasakmaris osifikacias da Zvlovani

labirinTis deformacias aqvs adgili. rig SemTxvevebSi sasmen ZvlebSi

kalciumi akumulirdeba, rac Zvlebis advilad msxvrevadobas ganapirobebs.

ovalur sarkmelSi kalcitebis Calagebam uzangis fexis fiqsacia SeiZleba

ganapirobos, rac Sua yuridan SigniTa yurisaken bgeraTa gadacemas

amuxruWebs. arasrulyofili osteogenezis calkeul SemTxvevebSi

sensonervuli tipis smenis daqveiTebac aRiniSneba.

urologiuri garTulebebi:

arasrulyofili osteogenezis arsebobisas pacientebs hiperkalciuria

aReniSnebaT. magram, Tirkmlebis kenWovani daavadebebi iSviaTad viTardeba,

da Tu arsebobs isic ZiriTadad eriTrocitebis xarjze gamovlindeba.

saSarde gzebis sistemis kedlebze datvirTvasTan dakavSirebiT

ultrabgeriTi litotrifsiis gakeTeba yovelTvis ar aris naCvenebi.

SeiZleba vivaraudoT, rom defeqturi I tipis kolagenisagan Semdgari

boWkoebi kedlis daqveiTebul stabilurobas ganapirobebs. Tumca ki, zusti

monacemebi ar arsebobs.

pulmonuri garTulebebi:

gulmkerdis yafazis deformaciis gamo filtvis calkeuli ubnis ventilacia

izRudeba, viTardeba ateleqtazi, pnevmonia da bronquli xisaTvis

damaxasiaTebeli obstruqcia. calkeul SemTxvevebSi filtvis

sisxlZarRvovani kalapotis Semcirebis gamo viTardeba pulmonuri

hipertenzia, ris Sedegadac yalibdeba Cor pulmonale. ukve CvilobaSic ki,

arastabiluri kedlis mqone patara gulmkerdis yafazis gamo, romlis

sunTqviTi moZraobebic paradoqsulia, SeiZleba hipoqsemiis Setevebs hqondes

adgili (gansakuTrebiT RamiT).

kardialuri garTulebebi:

SemaerTebeli qsovilis genarlizebuli defeqtis gamo cxovrebis

ganmavlobaSi viTardeba aortis fesvis gafarToeba an gulis sarqvelebis

ukmarisoba. msubuq SemTxvevebSic ki SeiZleba ganviTardes mZime kardialuri

10

garTulebebi. pulmonuri hipertenziiT gamowveuli filtvis arteriis

sarqvlis ukmarisobas SeiZleba Tan axldes sqoliozi da morecidive

pnevmoniebi.

hiperplaziuri Zvlovani korZis Camoyalibeba:

klinikuri gamovlinebis TvalsazrisiT msubuq da saSualo simZimis

SemTxvevebSi, rodesac pacients TeTri sklerebi aqvs, zogjer swrafad

viTardeba simsivne, romelic Sedgeba umwifari Zvlis xrtilisagan da

SemaerTebeli qsovilisagan. es hiperplaziuri korZi SeiZleba Tan axldes

motexilobas an isedac ganviTardes. misi warmoqmna, agreTve SeiZleba

qirurgiulma Carevamac gamoiwvios. hiperplaziuri korZi uxSiresad grZel

lulovan Zvlebzea lokalizebuli. mkvrivi mtkivneuli simsivneebi Zlier

mxurvale da SewiTlebulia. kliniko-laboratoriulad am dros gvaqvs

leikocitozi, momatebuli eds_i, Zlier momatebuli tute fosfataza. korZis

ganviTarebam SeiZleba avadmyofis sruli imobilizacia gamoiwvios. wlebis

ganmavlobaSi xdeba Warbi qsovilis neli regresi.

5. daavadebis diferencialuri diagnozi

arasrulyofili osteogenezis dros arsebuli da misTvis damaxasiaTebeli

klinikuri niSnebis arseboba saSualebas iZleva advilad moxdes

diferencialuri diagnostika msgavsi klinikuri da laboratoriuli

niSnebis mqone sxva daavadebebTan.

arasrulyofili osteogenezis dros arasodes ar gvxvdeba

rentgenologiurad ganieri epifizaruli xazebi, romlebic damaxasiaTebelia

raqitisaTvis. aseve, kortikaluri Sre raqitis dros ganleulia

umniSvnelod, kidurebze arsebuli deformaciebi ar aris mkafiod

gamoxatuli da arsebobis SemTxvevaSi gamrudebebi gvxvdeba mxolod

frontalur sibrtyeSi. paTologiuri tipis motexilobebi iSviaTia. kefis

Zvali ki raqitis dros ufro rbilia, vidre dausrulebeli osteogenezis

dros.

arasrulyofil osteogenezTan SedarebiT osteomalacia gvxvdeba ufro

iSviaTad, ZiriTadad biWebSi. motexilobebi osteomalaciis dros TiTqmis ar

xdeba, xolo Zvlis gamrudebebi xdeba Zvlebis sirbilis gamo. avadmyofebi am

daavadebis dros adinamiurebi arian. uCivian tkivils kidurebSi msgavsad

arasrulyofili osteogenezisa.

xolo axondroplaziis dros damaxasiaTebelia mikromelia, magram ar

gvxvdeba motexilobebi, romelic damaxasiaTebelia arasrulyofili

osteogenezisaTvis. rentgenologiurad kortikaluri Sre gasqelebulia,

Zvlovani qsovili kargad aris gamoxatuli. didi mniSvneloba aqvs mtevnebis

rentgenogramebs diagnostikisaTvis, radgan axondroplaziiT daavadebulebs

aqvT mokle da ganieri falangebi. damaxasiaTebelia unagiriseburi cxviri da

saxis uxeSi nakvTebi, romelic gamorCeulad gansxvavdeba arasrulyofili

osteogenezis dros arsebuli ganleuli da nazi saxis nakvTebisa da

SedarebiT patara Tavisagan.

Tandayolili sifilisis dros motexilobebis sixSire naklebia da Zvlebis

deformaciac ar aris ise mkveTrad gamoxatuli, rogorc arasrulyofili

osteogenezis dros. damaxasiaTebelia gavrcelebuli periostaluri

11

reaqciebi. sifilisuri gumebis arsebobis dros rentgenologiurad

aRiniSneba momrgvalo feris naTeli ubnebi.

hipofosfatazia vlindeba gacilebiT gvian da damaxasiaTebelia

generalizebuli osteoporozi, qveda kidurebis, xerxemlis deformaciebi da

paTologiuri motexilobebi. daavadebebis ZiriTadi ganmasxvavebeli niSania

hipofosfataziis dros sisxlSi tutefosfatazis donis mniSvnelovani

Semcireba an sarTod ar arseboba.

marfanis sindromis dros damaxasiaTebelia araxnodaqtilia, makromakria,

Tandayolili mezodermaluri distrofia, ganviTarebis anomaliebi:

dolixocefalia prognatia; Zabriseburi an soliseburi gulmkerdi; araproporciulad

grZeli da wvrili kidurebi, TiTebi, molaylaye saxsrebi, mxedvelobis

daqveiTeba, brolebis eqtopia, miopia, sielme.

rentgenologiurad damaxasiaTebelia: Zvlis metafizebis difuzuri

osteoporozi, kortikaluri Sris ganleva, wanazardebi terfis Zvlebze.

enles-danlos sindromic genetikuri daavadebaa, romelic ganpirobebulia II

tipis kolagenis struqturis darRveviT organizmis sxvadasxva sistemaSi. igi

klinikurad gamoixateba kanis hiperelastoziT, saxsrebis dazianebiT,

molaylaye saxsrebiT da Cveuli amovardnilobebiT. rentgenologiurad

enqondraluri gaZvalebis Seneleba, Tavis qalis araswori ganviTareba,

kompaqturi Tankbilva, laviwisa da falangebis akroosteolizi, sxiv-idayvis

sinostozi, brtyel terfianoba, megaezofagusi, saylapavis divertikuli,

diafragmis Tiaqrebi.

6. gamokvlevis sqema

diagnostireba efuZneba klinikur gamovlinebebsa da funqciur gamokvlevebs.

OI-s arsebobisas (mimarTvianobis algoriTmi)

travmatologiur

-orTopediuli

klinika

anamnezi

pacientis viziti

klinikaSi yovel 6

TveSi

(aucilebelia)

Terapiuli

mkurnaloba

wonis

kontroli

bisfosfonato

Terapia

fizikaluri

kvleva

upiratesad Ca-s

Semcveli

sakvebi

samkurnalo dieta

motexilobis

arsebobisas

deformaciebis

arsebobisas

viziti

orTopedTan

dRis reJimis

optimizacia

Ca-s preparatebi

fizikuri

reabilitaciis

saWiroebis

gansazRvra

axali

klinikuri

Civilebis

gaCenis

SemTxvevaSi

damatebiTi

kvlevebis

Catareba

kompiuteruli

tomografia

gulis eleqtro da

eqokardiografia encefalografia muclis Rrus

sonografia

aucilebelia: memkvidreobiTi faqtoris gamokiTxva, sadac aucileblad unda

Sediodes kiTxvebi axlo naTesavebSi smenis daqveiTebis, motexilobebis,

arasruli denticiis, zrdaSi CamorCenis arsebobis Sesaxeb.

fizikuri gamokvleva moicavs kidurebis sigrZisa da Tavis

garSemowerilobis Sefasebas, sadac yuradReba eqceva sxeulis

proporciulobas. aRniSnuli maCvenebeli fasdeba sxeulis zeda nawilis

(Tavi, torsi, zeda kidurebi) da qveda nawilis (qveda kidurebi)

Tanafardobas. amisaTvis aucilebelia yvela nawilis segmenturi sigrZis

gazomva, raTa gamovlenil iqnas arsebuli asimetria. OI-iT daavadebulebs

umeteswilad aReniSnebaT ufro grZeli zeda kidurebi, vidre qveda kidurebi

(normasTan SedarebiT).

gulmkerdis nawili aucilebelia gamokvleuli iqnas sqoliozis, kifozis, pectus excavatum da carunatum-is arsebobaze. CvilebSi unda gaizomos

yiflibandis zoma.

radiografiuli eqspertiza unda Catardes arCeviTad ConCxis sxvadsxva

nawilze. lateraluri da antero-posteriul poziciaSi Catarebuli

gamokvlevebis dros unda yuradReba mieqces: osteoporozis, deformaciebis,

axal da Zvel motexilobebis arsebobas, metafizur naTel zonebs da

sazrdel zonebs.

pirdapir da gverdiT proeqciaSi xerxemlis gamokvlevis dros yuradReba

unda mieqces: sqoliozs, xerxemlis malebis kompresias da malTaSoris

diskebis cvlilebebs.

Tavis qalis gverdiT proeqciaSi gamokvleva aucilebelia, raTa Seswavlili

iqnas Zvlebis konsolidaciis xarisxi.

mniSvnelovania malebis sxeulis DEXA (densitometriuli kvleva ormagi

rentgeno-absorbciuli meTodiT) gamokvlevis Catareba, raTa zustad

dadgindes osteoporozis xarisxi, radgan II, III da IV tipis OI-s dros

Zvlovani matriqsis xarisxobriv defeqts aqvs adgili. aRniSnuli kvleva ki

saSualebas iZleva arapirdapiri gziT dadgindes Zvlovani qsovilis rogorc

xarisxobrivi, ise raodenobrivi cvlilebebi.

prenataluri ultrabgeriTi gamokvleva orsulobis me-18, 24-e kviraze, OI-s adreuli gamovlinebis saSualebas iZleva.

amniocenteziT SesaZlebelia dnm-is da rnm-is diagnostika, rac saSualebas

iZleva diagnozis dazustebisa.

yvela saeWvo SemTxvevaSi, rodesac ver xerxdeba diagnozis dadastureba,

aucilebelia Catardes biofsiuri kvleva. kolagenis gamokvleva da misi

histologiuri Seswavla, iZleva „kategoriuli“ diagnozis dasmis

saSualebas.

7. mkurnalobis sqema

arasrulyofili osteogenezis mkurnaloba tardeba kompleqsurad:

Terapiuli mkurnaloba, orTopediuli RonisZiebebi (konservatiuli da

qirurgiuli) da fizikuri reabilitacia.

14

gamokvlevebi Terapiis dawyebamde gamokvlevebi Terapiis Semdeg

densitometria -

rentgenografia -

dinamometria -

goniometria -

sisxlis suraTi Ca, P , kreatinini. tute fosfataza Ca, P ,

Sardi Ca, P , kreatinini Ca, P , kreatinini

Terapiuli mkurnalobisaTvis dRes-dReobiT warmatebiT gamoiyeneba

bisfosfonatebis jgufis preparatebi (1, 3-7, 14 sarw. I, II done).

Zvlovani qsovili swrafad akavebs bisfosfonatebs. intravenurad Seyvanili

dozis 20-80% koncertrirdeba Zvlis aqtiur zedapirze, xolo danarCeni

SardTan erTad gamoiyofa metabolizmis gareSe. misi gamoyofa biliaruli

sistemiT ar xdeba. peroralurad miRebuli bisfosfonatebis absorbcia

Seadgens 0,5_8% da mcirdeba saWmlis momnelebel sistemaSi sakvebis an

kalciumis arsebobis gamo, radgan isini boWaven preparats nawlavSi.

ConCxidan bisfosfonatebi gamoiyofa Zalian nela, kerZod zogierTi maTganis

naxevrad daSlis dro Seadgens daaxloebiT erT wels.

infuziis Semdeg Zvlovan qsovilSi Calagebuli bisfosfonatebi Trgunaven

Zvlis rezorbcias romelic ganpirobebulia osteoklastebiT.

meore Taobis bisfosfonatebis upiratesoba pirvel TaobebTan SedarebiT

aixsneba imiT, rom isini aaqtiureben osteoblastebis funqcionirebas.

yovelive amis Sedegad balansi Zvlis Sewovasa da formirebas Soris, anu

osteoklastebsa da osteoblastebs Soris osteoblastebis sasargeblod

gadaixreba, rac xels uwyobs Zvlovani qsovilis meti raodenobiT

warmoqmnas.

warmogidgenT arasrulyofili osteogenezis Terapiuli mkurnalobis

dReisaTvis arsebul da aprobirebul protokols. medikamenturi

mkurnalobis yvelaze efeqtur preparats warmoadgens bisfosfonatebis

jgufis warmomadgeneli pamidronati.

Terapiuli koncefcia (monrealis protokoliT)

• yoveli cikli Sedgeba pamidronatis 3 infuziisagan, romelic unda

gakeTdes zedized, 3 dRis ganmavlobaSi;

• pamidronatis piveli cikli keTdeba 3 Tvis asakSi. pirveli infuziis

dozaa – 0.25 mg/kg. xolo meorisa da mesamis – 0.5 mg/kg;

• meore da Semdgomi ciklebi sruldeba yovel 8 kviraSi erTxel, 24 Tvis

asakis miRwevamde. doza – 0.5 mg/kg, samive dRes;

• 2-dan 3-wlis asakamde: ciklis gameoreba xdeba yovel 3 TveSi erTxel.

doza – 0.75 mg/kg yovel sam dReSi erTxel;

• 3 wlis asakidan: cikli meordeba yovel oTx TveSi erTxel. doza – 1

mg/kg.

maqsimaluri doza aris 9 mg/kg weliwadSi

pamidronatis maqsimaluri doza: 60 mg/dReSi Х 3 =180 mg

15

dozirebis sqema meore da yoveli Semdgomi infuziisaTvis

(pirveli ciklis pirveli infuziisaTvis mizanSewonilia mxolod naxevari

odenobis miReba!)

bavSvis wona

kg

pamidronatis

doza

mg

0.9% Na Cl raod. romelSic unda

gaixsnas

pamidronati

ml

infuziis siCqare

(wveTebis

raodenoba

wuTSi)

3 1.5 20 5

3.5 1.8 22 5.5

4 2 25 6.5

4.5 2.3 30 7.5

5 2.5 33 8

5.5 2.8 35 9

6 3 40 10

7 3.5 45 11

8 4 50 13

9 4.5 55 14

10 5 60 15

11 5.5 70 17

12 6 75 19

13 13 80 20

infuziis periodSi:

• Zalze mniSvnelovania: infuziis xsnaris sakmarisi ganzaveba da

infuziis siCqare, rogorc cxrilSia mocemuli. zedmetma

koncentraciam nazavSi SesaZloa gamoiwvios Tirkmelebis funqciis

darRveva da infuziis maRali siCqare;

• pirveli ciklis pirveli infuziis Semdeg xSirad warmoiSoba e.w.

`reaqciis mwvave faza~, rogoricaa – sicxe, gripozuli simptomebi,

swrafi egzanTema, sunTqvis sixSiris momateba: xangrZlivoba 2 dRemde.

maRali sicxianobis dros mkurnaloba standartulia, mag:

paracetamolis sanTlebi Per Reqtum;

• hipokalcemia gansakuTrebiT xSirad gvxvdeba pirveli infuziis dros

da mis Semdeg (xSirad iwvevs saerTo kalciumis dacemas daaxloebiT

1.8-1.9 mmol-mde); amitom rekomendirebulia rZe. mxolod klinikuri

hipokalcemiis simptomatikis dros, rogoricaa kunTis tonusis

16

momateba (krunCxva) da konvulsia, aucilebelia kalciumis

substitucia. iSviaTad 1 ml 10%-iani Ca glukonati 1kg wonaze.

bisfosfonatebiT mkurnalobis optimaluri xangrZlivoba 2-3 welia.

mkurnalobis Sewyvetis Semdeg preparati kidev 2 weli kumulirdeba ZvalSi

da agrZelebs Tavis moqmedebas. swored mkurnalobis pirveli ori wlis

ganmavlobaSi klinikurad da densitometriulad vlindeba moqmedebis

maqsimaluri dadebiTi efeqti. mkurnalobis Semdgomi gagrZeleba aRar iZleva

sasurvel Sedegs da izrdeba preparatiT mkurnalobis garTulebebis gviani

gamovlenis riski. es riski ufro maRalia pamidronatis xangrZlivad

gamoyenebisas bavSvis intensiuri zrdis periodSi (pubertatuli asaki) (15, 16

sarw. II done).

aqve unda aRiniSnos, rom dadasturda faqti, rom pamidronatiT xangrZlivi

mkurnalobisas ferxdeba Zvlis konsolidacia osteotomiuri operaciebis

Semdeg (13 sarw. III done)

operaciuli mkurnalobis saWiroeba ZiriTadad vlindeba makoregirebel

operaciebSi lulovan Zvlebze, arsebuli deformaciebis gamo.

operaciuli mkurnalobis specifika da Tavisebureba mdgomareobs imaSi, rom

gamoiyeneba mxolod intramedularuli osteosinTezebi specialuri

safiqsacio saSualebebiT, yovelgvari kompresiuli firfitebisa da garegani

safiqsacio aparatebis gamoyenebis gareSe.

dReisaTvis aRniSnul daavadebas warmatebiT ikvleven da mkurnaloben

msoflios bevr ganviTarebul qveynebSi. rogoricaa: germania, kanada,

espaneTi, italia.

OI-s specifiuri klinikuri da Tvisobrivi maxasiaTeblebidan gamomdinare,

mkurnalobaSi Terapiul kursTan (bisfosfonato Terapia) erTad udidesi da

SeiZleba iTqvas gadamwyveti mniSvneloba eniWeba operaciul mkurnalobas,

riTac SesaZlebelia Tavidan iqnes acilebuli an minimumamde mainc

dayvanili am bavSvebis invalidoba (8, 17, 18 sarw. II-III done).

operaciuli mkurnalobisas gamoiyeneba ramodenime tipis Reroebi:

1. kirSner-viresis Cxirebi 2. elastiuri Reroebi (ESIN)

3. teleskopiuri Reroebi (Bailey-Dubow)

17

am safiqsacio saSualebebidan upiratesoba eniWeba teleskopiur Reroebs. is

iZleva aramarto myar fiqsacias aramed bavSvebis zrdis paralelurad

icvlis sigrZiv zomebs. ase, rom teleskopiuri Rero SesaZlebelia mozardis

sxeulSi moTavsdes xangrZlivi periodis ganmavlobaSi, ise, rom zrdis

process xeli ar SeuSalos.

warmatebiT gamoiyeneba teleskopiuri Reroebi „FASSIER-DUVAL“-is mier

mowodebuli. aRniSnul sistemas avtorebi mcire upiratesobas aniWeben sxva

teleskopiuri Reroebisagan gansxvavebiT, imis gamo rom, is orive boloTi

ixraxneba lulovani Zvlebis metafizebSi, rac Reros migrirebas TiTqmis

gamoricxavs.

18

FASSIER – DUVAL

TELESCOPIC IM SYSTEM

reabilitacias mniSvnelovani adgili ukavia arasrulyofili osteogeneziT

daavadebulTa mkurnalobaSi (9, 11 sarw. III done).

amocanebi:

• dazianebul kidurSi sisxlis mimoqcevis gaumjobeseba;

• imobilizaciisagan Tavisufal saxsrebSi moZraobis SenarCuneba;

• dazianebuli kiduris kunTebis tonusis SenarCuneba;

• yavarjnebiT gadaadgilebis swavleba TabaSiris naxveviT

imobilizaciisas (!!! – gansakuTrebuli sifrTxile);

• woliTi reJimis SemTxvevaSi (ConCxovani daWimva) profilaqtika da

brZola hipodinamiiT gamowveul adreul garTulebebTan, rogoricaa

traqeobronqiti, ateleqtazi, pnevmonia, Trombozi, nawlavebis atonia

da sxva.

19

am periodisaTvis samkurnalo fizkulturis ZiriTadi saSualebebia:

• statiuri da dinamiuri sunTqviTi varjiSebi aqcentirebuli

diafragmul sunTqvaze da gaxangrZlivebul amosunTqvaze;

• pasiuri da aqtiuri varjiSebi aradazianebuli kidurisaTvis;

• izometruli daZabvis varjiSebi (2-3 wami) aradazianebuli

kidurebisaTvis;

• ideomotoruli varjiSebi;

• damxmare saSualebebis gamoyeneba.

zemoT aRwerili Terapiuli mkurnalobis protokolis ar\ver Sesrulebis

SemTxvevaSi SesaZlebelia qvemoT moyvanili alternatiuli protokolebis

gamoyeneba

mowodebulia pamidronatiT mkurnalobis alternatiuli sqemebi:

aseve 6 wlis askis zeviT gamoiyeneba neridronati 2mg/kg intravenurad 30 wT-

is ganmavlobaSi, yovel 3 TveSi, an etidronati abebis saxiT, sxeulis wonis

Sesabamisi dozirebiT (22 - sarw. III done)

somatotropuli preparatebiT mkurnaloba grZeldeba 1 Tve. preparati

keTdeba kunTebSi, 4 erTeuli kviraSi samjer (kursze 12-15 ineqcia).

somatotropul preparatebTan erTad iniSneba antioqsidantebi, kalciumis da

fosforis marilebi, vitamini D asakis Sesabamisad, somatotropuli

preparatebis efeqtis potencirebis da mineralebis ZvalSi utilizaciis

mizniT. (21 -sarw. III done)

somatotropuli preparatebiT kursis CamTavrebis Semdeg iniSneba Zvlis

mineralizaciis stimulatorebi.

paralelurad iniSneba eleqtroforezi kalciumis marilebiT lulovan

Zvlebze, induqto- da magnitoTerapia.

pamidronatiT mkurnalobis protokoli (omaha)

► <2 wlis asaki ═0.37 mg/kg/dReSi, 3 momdevno dRe yovel 2 TveSi

► 2-3 wlis asaki ═ 0.56 mg/kg/dReSi, 3 momdevno dRe yovel 3 TveSi

► >3 wlis asaki ═0.75 mg/kg/dReSi, 3 momdevno dRe yovel 4 TveSi

4.5 mg/kg/weliwadSi

pamidronatis maqsimaluri doza:

45 mg/dReSi Х 2 =90 mg

20

8. reabilitacia / meTvalyureoba

arasrulyofili osteogeneziT daavadebuli bavSvi avadmyofobisa da

SezRuduli SesaZleblobebis arsebobis miuxedavad aucilebelia sul

moZraobaSi iyos. SiSi imisa, rom motexilobebis arsebobis sixSire

damokidebulia fizikur aqtivobaze - usafuZvloa, radgan motexilobebis

umravlesoba spontanurad viTardeba – yovelgvari Zaldatanebis gareSe. rac

ufro Zlieria kunTovani sistema Zvlis garSemo miT iSviaTad viTardeba

motexiloba.

motexilobebi, romlebic umetes wilad dabadebis Semdeg iwyeba,

ganuviTarebeli kunTovani sistema (daavadebiT ganpirobebuli da umoZraobis

xarjze) da mSoblebis SiSi, rom aqtiuri da pasiuri moZraobiT Zvlis kidev

ufro meti motexiloba gamoiwveva, arc Tu ise iSviaTad iwvevs imas, rom

arasrulyofili osteogeneziT daavadebuli Cvili bavSvebi did dros

loginSi atareben da amitom maTi normaluri, socialuri da fizikuri

ganviTareba CamorCeba:

motexilobebi hipodinamia

kunTebis sisuste fizikuri ganuviTarebloba

mSoblebis SiSi socialur ganviTarebaSi CamorCena

• SuSis bavSvebs zedmetad frTxilad ar unda movepyraT, aramed,

ramdenadac es SesaZlebelia rogorc janmrTel bavSvs ise moveqceT

da a.S.;

• maTTvis nu avirCevT viwro tansacmels. viqonioT tansacmeli

romelic advilad romelic advilad, Zaldatanebis gareSe SeiZleba

gavxadoT;

• veridoT uecar mkveTr da brunviT moZraobebs;

• ar daviWiroT xelSi bavSvi kidurebiT, aramed mis sxeulsa da Tavs

gavukeToT sayrdeni;

• rogorc ki Cvils SeeZleba moZraobis aqtiurad Sesruleba, saWiroa

amaSi xeli SevuwyoT, moZraobebi TviTon rom Seasrulos.

9. gaidlainis gadasinjvis da ganaxlebis vada

gaidlainis gadasinjvis da ganaxlebis vada sasurvelia ar aRematebodes 2

wels, radgan Zalian bevri ram arasrulyofili osteogenezis paTogenezsa

da mkurnalobaSi Seswavlis fazaSia da saWiroebs informaciis droul

moZiebasa da damuSavebas.

21

10. gaidlainis miRebis xerxi / wyaro

zemoT aRniSnuli gaidlaini damuSavda da Sejerda ZiriTadad

sazRvargareTis klinikebsa da samecniero literaturaSi moZiebuli

masalebiT (masalebs gaaCnia mtkicebulebis maRali done).

mimdinareobs kvlevebi da eqsperimentebi germaniaSi, kanadaSi, italiasa da

espaneTSi, romlebic jer ar dasrulebula.

dRes-dReobiT mowodebulia nacionaluri gaidlainebi, romlebic eyrdnoba

mimdinare kvlevebs da mudmiv ganaxlebis procesSia. (12, 19 sarw. II-III done).

11. alternatiuli gaidlaini - ar arsebobs.

12. gamoyenebuli literatura

1. Plotkin H., Rauch F., Bishop N., Monpetit K., Ruck-Gibis J., Travers R., Glorieux F.Pamidronate treatment of severe Osteogenesis Imperfecta in children under 3 years of age J Clin Endocrinol Metab 2000; 85 (5) : 1846-1850 ( sarw. I done);

2. Marlowe A. Pepin MG. Byers PH. (2002)Testing for osteogenesis imperfecta in cases of suspected non-accidental injury. Journal of Medical Genetics. 39(6):382-6. (sarw. II

done); 3. E Astrom, S Soderhall. Beneficial effect of long term intravenous bisphosphonate treatment

of osteogenesis imperfecta Arch Dis Child 2002;86:356–364 (sarw. II done; 4. Frank Rauch, Rose Travers, Horacio Plotkin, and Francis H. Glorieux .The effects of

intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta J. Clin. Invest. 110:1293–1299 (2002). (sarwm. I done);

5. Marni J. Falk, Shauna Heeger, Katherine A. Lynch, Kathleen R. DeCaro, Deborah Bohach, Karen S. Gibson and Matthew L. Warman. Intravenous Bisphosphonate Therapy in Children With Osteogenesis Imperfecta Pediatrics 2003;111;573-578 (sarw. II done);

6. Rauch F. Plotkin H. Travers R. Zeitlin L. Glorieux FH. (2003). Osteogenesis Imperfecta Types I, III, and IV: Effect of Pamidronate Therapy on Bone and Mineral Metabolism The Journal of Clinical Endocrinology & Metabolism 88(3):986–992 (sarw. I done);

7. Sakkers R. Kok D. Engelbert R. van Dongen A. Jansen M. Pruijs H. Verbout A. Schweitzer D. Uiterwaal C. (2004) Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study.. Lancet. 363(9419):1427-31 (sarw. II done);

8. Panzica M. Garapati R. Zelle B. Krettek C. Tscherne H. Pape HC. (2004) Combination of femoral fracture treatment and corrective osteotomy in a child with osteogenesis imperfecta. Archives of Orthopaedic & Trauma Surgery. 124(5):341-5. (sarw. II done);

9. Engelbert RH. Uiterwaal CS. Gerver WJ. van der Net JJ. Pruijs HE. Helders PJ. (2004) Osteogenesis imperfecta in childhood: impairment and disability. A prospective study with 4-year follow-up. Archives of Physical Medicine & Rehabilitation. 85(5):772-8.(sarw. III done);

10. Cabral WA. Marini JC. (2004) High proportion of mutant osteoblasts is compatible with normal skeletal function in mosaic carriers of osteogenesis imperfecta. American Journal of Human Genetics. 74(4):752-60 (sarw. II done);

11. Gerber, L.H., H. Binder, J.Weintrob, D.K.Grange, J. Shapiro, W.Fromherz, R.Berry, A.Gomway, S.Nason, and J.Marini. “ Rehabilitation of Children and Infants with osteogenesis imperfecta. A program for Ambulation” Clin Orthop, no.251 (1990):254-258 (sarw. III done);

22

12. Antoniazzi F., M.Mottes, P.Fraschini, P.C.Brunelli, and L.Tato. “Osteogenesis imperfecta: PPractical Treatment Guidelines”. Paediatr Drugs2, no.6(2000):465-88 (sarw.II done);

13. Craig FJ Munns,1 Frank Rauch,1 Leonid Zeitlin,1,2 Franc.ois Fassier,3 and Francis H Glorieux. Delayed Osteotomy but Not Fracture Healing in Pediatric Osteogenesis Imperfecta Patients Receiving Pamidronate JOURNAL OF BONE AND MINERAL RESEARCH Volume 19, Number 11, 2004 August 23, 2004; doi: 10.1359/JBMR.040814 (sarw. III done);

14. Anne D Letocha, Holly L Cintas, James F Troendle, James C Reynolds,Christopher E Cann, Edith J Chernoff , Suvimol C Hill, Lynn H Gerber, and Joan C Marini. Controlled Trial of Pamidronate in Children With Types III and IV Osteogenesis Imperfecta Confirms Vertebral Gains but Not Short-Term Functional Improvement JOURNAL OF BONE AND MINERAL RESEARCH Volume 20, Number 6, 2005 January 18, pages 977-986 (sarw. II done);

15. Frank Rauch, Craig Munns, Christof Land, and Francis H. Glorieux. Pamidronate in Children and Adolescents with Osteogenesis Imperfecta: Effect of Treatment Discontinuation The Journal of Clinical Endocrinology & Metabolism 91(4):1268–1274 (sarw. II done);

16. Frank Rauch, Rose Travers, and Francis H. Glorieux. Pamidronate in Children with Osteogenesis Imperfecta:Histomorphometric Effects of Long-Term TherapyThe Journal of Clinical Endocrinology & Metabolism 91(2):511–516 (sarw. II done);

17. Mehdi Aarabi, Frank Rauch, Reggie C. Hamdy, Francis Fassier. High Prevalence of Coxa Vara in Patients with Severe Osteogenesis imperfecta. J Pediatr Orthop, Volume 26, № 1, 24-28 Jan-Feb 2006 (sarw,III done);

18. L.Zeitlin, F. Fassier and F. Glorieux. Modern approach to children with osteogenesis imperfecta. Journal of Pediatrics Orthopedics B 2003 , 10: 77-87 (sarw, III done);

19. Engelbert R.H., H.E.Pruijs, F.A. Beemer, and P.J.Helders. „ Osteogenesis imperfecta in Childhood: Treatment Strategies“ Arch Phys Med Rehabil 79, no.12(1998):1590-4 (sarw. II done);

20. Panzica M. Garapati R. Zelle B. Krettek C. Tscherne H. Pape HC. (2004) Combination of femoral fracture treatment and corrective osteotomy in a child with osteogenesis imperfecta. Archives of Orthopaedic & Trauma Surgery. 124(5):341 (sarw.III done);

21. Noda H. Onishi H. Saitoh K. Nakajima H. (2002) Growth hormone therapy may increase fracture risk in a pubertal patient with osteogenesis imperfecta. Journal of Pediatric Endocrinology. 15(2):217-8.(saw, III done) ;

22. Adami S. Gatti D. Colapietro F. Fracassi E. Braga V. Rossini M. Tato L. (2003) Intravenous neridronate in adults with osteogenesis imperfecta. Journal of Bone & Mineral Research. 18(1):126-30 (sarw. III done).

13. avtorTa jgufi

arasrulyofili osteogeneziT daavadebulTa daxmarebis asociacia `SuSis bavSvebi~:

⇒ xaTuna saganeliZe _ medicinis mecnierebaTa doqtori, q.

Tbilisis samedicino akademia;

⇒ luxum Wanturia – travmatolog-orTopedi s.s. ,,travmatologi~;

⇒ maia kvirkvelia _ eqimi-reabilitologi.

eqspertebi:

⇒ dimitri wverava – profesori; Tbilisi samedicino akademia

23

⇒ irakli favleniSvili - profesori., Tbilisis saxelmwifo

universiteti;

⇒ saojaxo medicinis profesionalTa kavSiri _ irina qarosaniZe;

⇒ lela woworia _ saqarTvelos Sromis, janmrTelobisa da

socialuri dacvis saministros janmrTelobis dacvis

departamenti;

⇒ Tea TavidaSvili _ saqarTvelos Sromis, janmrTelobisa da

socialuri dacvis saministros janmrTelobis dacvis

departamenti.