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1 대한치과재료학회지 42(2) : 83-94, 2015 ISSN: (Print); (Online) Available online at QLF 와 SEM 을이용한교정환자에서불소바니쉬의법랑질탈회예방효과평가 <Abstract> 이한철, 김은정, 이재영, 백대일, 진보형 서울대학교치의학대학원예방치학교실 Preventive effect evaluation of fluoride varnish demineralization in orthodontic patients using quantitative light-induced fluorescence(qlf) and scanning electron microscope(sem) Han-Chul Lee, Eun-Jeong Kim, Jae-Young Lee, Dai-Il Paik, Bo-Hyoung Jin Dept. of Preventive and Social Dentistry, School of Dentistry, Seoul National University, Seoul, , Korea. Orthodontic appliances are induced deposition of dental plaque and make poor oral hygiene. During orthodontic therapy, appliances make opportunity of demineralization. For this reason, various fluoride-products are used to prevent such a demineralization. Among the fluoride-products, fluoride varnish are less dependent on patient cooperation and release for a long time in the form of thin films. Quantitative light-induced Fluorescence (QLF) is good to observe the enamel demineralization in vivo. Therefore, the purpose of this study was to investigate preventive effect of fluoride varnish in orthodontic patients using QLF methods and scanning electron microscope(sem). This study was conducted to test 28 teeth scheduled for premolar extraction(irb No. S-D ). An experimental group of premolars(#14 or #15, #34 or #35) was equipped with an orthodontic band after fluoride varnish applying, while a control group of premolars(#24 or #25, #44 or #45)was just equipped with an orthodontic band. Left side premolars(#24 or #25, #34 or #35) removed after 4 weeks. After remaining premolars(#14 or #15, #44 or #45) had applicated fluoride varnish at 4 weeks and evaluated effect remineralization. Comparing the demineralization amount is measured using QLF and SEM image analyzed the degree of preventive effect. There were significantly different of mineral reduction between before and after the application in the control group. However, the experimental group did not have any significant difference of mineral reduction between before and after the application. The difference between the experimental group and the control group was difference in the mandible than the maxilla. The experimental group applied fluoride varnish had less mineral decrease in demineralizing environment, this could be considered caries-resistant was larger than the control group not applied of fluoride varnish. However, there were no significant difference reapplication effect at 8 weeks. For orthodontic patients, fluoride varnish can prevent demineralization of the orthodontic devices by applying in advance. Key words: Fluoride varnish, Orthodontic patients, QLF, SEM Ⅰ. INTRODUCTION 교정장치는치면세균막의침착을유도하며, 구강위생을나 * Correspondence: 진보형서울시종로구연건동 28 서울대학교치과대학예방치학교실 Tel: , Fax: jjbh@snu.ac.kr Received: Mar 26, 2015; Revised: Apr 26, 2015; Accepted: Apr 26, 2015 쁘게만든다. 치료기간동안그리고치료예약기간의간격은 탈회진행의기회를제공하며환자자신에의한관리가잘 이루어지지않는경우브라켓주변의치태축적과치석형성이 일어나기쉽고, 이로인해치은증식, 치은염, 그리고치아우식 증등이발생할수있다. 또한치면세균막의축적으로인해 * 이논문은 2013 년도 베리콤의재원으로서울대학교산학협력단의지원을받아수행된연구사업임 (NO ).
2 교정치료를받는환자의백색반점의발생은 50% 까지보고되고있으며, 이것은밴드혹은교정장치후이미 4주에발현될수있다 (Heintz와 Georg, 1999; Evrenol 등, 1999). 백색병소의초기법랑질우식병소는우식와동이형성되기전의법랑질탈회현상이며이러한현상은이후진행우식병소로이환될수있다. 이러한초기우식과정에서법랑질표층에탈회와재광화가반복적으로이루어지는현상을보이는데 (Silverstone, 1967), O Reilly 와 Featherstone(1987) 의연구에따르면교정장치주변탈회부위에불소함유 mouth rinse를사용하여건전법랑질과초기우식병소에탈회예방효과를보여주었다. 또한 Geiger 등 (1992) 은오랜기간교정환자에게 fluoride mouth rinse를사용하게한뒤같은결과를얻었다. 불소에대한국소도포방법은교정환자의브라켓장치주변의탈회를막는용도로널리사용되고있으며 (Pithon 등, 2014), 여러가지불소국소도포방식중바니쉬의효과를비교해본연구들로 Ogaard 등 (1996) 은불소바니쉬도포유무에따라법랑질병소의형성을평가한뒤, 바니쉬사용으로병소깊이의 48% 감소를발견하였다. Shobha 등 (1987) 과 Tewari 등 (1990) 은불소겔보다불소바니쉬가더우수한우식예방효과를보았다고하였으며, Seppa 등 (1995) 은불소겔과불소바니쉬의예방효과의차이의유의성을없다고하였다. Bravo 등 (1997) 은불소바니쉬와치면열구전색제를비교한연구에서치면연구전색제가우식예방에효과적이라고하였다. 다양한불소제품 ( 전신적인형태, 겔, 바니쉬, 치약, mouth-rinse) 중에, 바니쉬가가장사용하기쉬우며환자협조도에덜의존적이다. 또한바니쉬는치아표면에부착하여얇은막의형태로오랜시간불소를방출한다 (Gorton 와 Featherstone, 2003; Todd 등, 1999). Beltran-Aguilar 등 (2000) 은불소바니쉬는의료용기구뿐아니라일상적인우식예방제재로써도승인이되었으며, 안전하고효과적이라고설명하였다. 그러므로치아우식증에이환되기쉬운고위험군환자에서의불소배합바니쉬는효과적이라할수있겠다. 환자치아의법랑질탈회정도를임상적으로평가하기용이한 Quantitative Light-Induced Fluorescence(QLF) 는비침습적인방법으로법랑질탈회량을측정할수있는 방법이다 (Jun 등, 2010; Nakata 등, 2009). 또한 Diagnodent R 보다우식관측이정확하며, confocal laser microscopy 와비교해도손색이없다고하였다 (Verdonschot 와 Angmar- Mansson, 2003). QLF는치아표면에녹청색광을비추어형광을발산하는데탈회부위에서의형광산란량이증가되어법랑질보다어두워지는특성을이용하여무기질소실량을수치화하여나타낸다 (Angmar-Månsson 과 ten Bosch, 2001). 건전한법랑질조직에서녹색이우세하게나타나고, 탈회된법랑질에서는자가형광성이감소, 그양은고안된프로그램을통해정량화되고무기질소실량 (ΔQ) 을측정할수있다 (Stookey, 2005). 본연구에서는이러한형광량변화량과무기질소실에관한진단용으로사용되는 QLF를이용하여, 4, 8주간교정환자에게불소바니쉬를적용한후법랑질의탈회예방효과와재광화정도를평가하였고, 발거된치아를 scanning electron microscope 을이용하여, 표면양상을관측하였다. Ⅱ. MATERIALS AND METHODS 이연구는소구치교정발치예정인환자 7명을대상으로실험을진행하였다. 대상자의발치예정소구치 4개씩총 28개를대상으로실험소구치군 14개에제조사에서권장하는방법인방습후 4분간브러쉬를이용하여불소바니쉬 (V-varnish, 베리콤, 한국 ) 를도포한뒤밴드를장착하였고, 대조소구치군 14개는밴드만장착한후, 4주뒤에밴드를제거한후형광량을측정하였다. 이후상악좌측소구치와하악좌측소구치는발거하여, 교정치료를진행하였고, 상악우측소구치와하악우측소구치에불소바니쉬를도포하여불소바니쉬의반복도포시효과와탈회된치아에도포시효과를평가하였다. 실험소구치군과대조소구치군의형광량비교는실험전형광량과 4주와 8주후형광량을 Quantitative Light-Induced Fluorescence(QLF, QLF Pro, Inspektor Research System BV, Amsterdam, Netherlands) 를이용하여각각측정한후탈회정도와바니쉬의예방효과정도를관찰, 비교하였고, scanning electron microscope(sem, S-4700, HITACHI, 84
3 Table 1. QLF measurement site by group QLF measurement site QLF taking after 4 weeks QLF taking after 8 weeks Upeer left premolar Banding after no treatment Premolar extraction at 4 weeks Control group Lower right premolar Banding after no treatment Banding after application fluoride varnish at 4 weeks Experimental group Upper right premolar Banding after fluoride varnish taking Banding after reapplication fluoride varnish at 4 weeks Lower left premolar Banding after fluoride varnish taking Premolar extraction at 4 weeks Tokyo, Japan) 을이용하여발거된치아의표면을관측하였다 연구대상선정기준교정진행예정인환자중소구치발치가예정된자중다음에해당하는사람을연구대상으로하였다. - 만 13세이상 55세이하로전신질환이없는자 - 소구치협면에우식병소나 white spot이없는자 - 교정장치에알러지가없는자 1.2. 연구대상제외기준 - Lὅe and Silness Gingival index 치은검사기준에따라심한치주질환이있는환자 (GI index 3) - Saliva-check mutans(gc, Tokyo, Japan) 를이용해 positive 한경우에속하는우식활성도가높은환자 - 연구에동의하지않는환자본연구는시행전서울대학교치의학대학원의임상실험연구윤리위원회 (Institutional Review Board) 에의해승인을받았다 (IRB S D ) visit 1(screening, -2주 ~0일 ) 임상시험의선정 / 제외기준에적합하다고판단되는모든 환자는시술하기전에다음의순서에따라스크리닝하였다. - 이시험에참여하는지원자는피험자동의를얻기위한설명을거쳐자유의사에의해피험자동의서에서면동의를한후시험에참여하였다. - 불소바니쉬적용의대상환자로서의적합성을파악하기위해피험자이니셜, 성별, 생년월일과같은인구학적정보와본제품에대한기왕력유무, 임신여부, 전신질환등신체상태검사와병력, 치과력을조사하였다. - 스크리닝을통하여선정 / 제외기준적합여부를평가하여시험참여가적합한경우에피험자에게정해진식별코드를부여하였다 visit 2( 적용일, 기준일 ) 스크리닝방문시실시된선정 / 제외기준에적합한피험자에한하여 Quantitative light-induced fluorescence (baseline) 를이용하여실험소구치와대상소구치의형광량을측정하였다 visit 3(28일 ±5일 ) 밴드를제거한뒤에상악우측소구치, 상악좌측소구치, 하악좌측소구치, 하악우측소구치의형광량을측정한후교정치료의진행을위하여하악좌측소구치와상악좌측소구치를발거하였고하악우측소구치와상악우측소구치 85
4 Table 2. Evaluation period in accordance with check list Check list Evaluation period Screening visit 1 (-2wks~0day) visit 2 ( 0day ) Treatment and evaluation period visit3 ( 4wks ) visit4 (8wks) Informed consent o Medical dental history taking Inclusion/Exclusive criteria judgement o o QLF taking o o o SEM taking o o 에불소바니쉬를도포하였다. 또한 4주차에발거된소구치의표면을 SEM을이용하여관측하였다 vist 4(56일 ±5일 ) visit 3 과정에서하악우측소구치와상악우측소구치의형광량을측정하였다. 또한 8주차에발거된소구치의표면을 SEM을이용하여관측하였다. 3. 통계분석실험전후의형광량변화량은 T-검정을이용하여분석하였으며, 통계적유의성판정을위한유의수준은 5% 로설정하였다. 분석은 SPSS(SPSS 19.0 for window, SPSS Inc., Chicago, IL., USA) 프로그램을이용하였다. Ⅲ. RESULTS 각교정환자들에게불소바니쉬를 4주간적용한결과형광량 (ΔF) 은 Table 3과같다. 대조군에서는불소바니쉬도포전과불소바니쉬도포 4주후의유의한차이가발생되었고, 실험군에서는도포전후의유의한차이가발생하지않았다. 대조군과실험군의형광량변화량 (ΔΔF) 을통계적으로분석해보니 4주차에서두군간의통계적으로유의한차이가발생하였다 (P<0.05). 실험군과대조군을상악과하악으로층화하여분석한결과 Table 4와 Table 5와같았다. 상악에서는대조군과실험군사이의형광량변화는통계적으로유의한차이가없었다 (P>0.05). 하악에서대조군과실험군사이의형광량변화는대조군에서형광량이감소하였고실험군에서형광량이증가하였으며, 통계적으로유의한차이가있었다 (P<0.05). 1. 불소바니쉬재도포시형광량변화량상악에서의불소바니쉬재도포시 4주에서보다 8주에서형광량이미묘하게감소하여탈회가진행되는경향으로나타났으나통계적으로유의하지않았다 (P>0.05) 하악에서 4주간탈회환경후불소바니쉬도포시 4주에서보다 8주에서형광량이증가하여재광화되는경향을보였으나, 통계적으로유의하지않았다 (P>0.05). 4주차에발거된치아의 SEM 이미지촬영결과불소바니쉬를도포한실험군에서평활한형태의상이나타난반면, 불소바니쉬를적용하지않은대조군의치면에서법랑질탈회가관찰되었다. 8주차에발거된치아의 SEM 이미지촬영결과초기와 4주차에반복적으로불소를도포한실험군에서평활한형태의상이나타났으며, 초기부터 4주차까지자연탈회된후 4주차에서만불소바니쉬를도포한대조군의법랑질표면에서평활하고재광화된형태의구상물질을확인할수있었다. 86
5 Table 3. Fluorescence difference at 4 weeks Group Name N ΔF(%)* Before treatment After treatment ΔΔF(%) Control group Upeer left ± ± ± 2.64 Lower right ± ± ± ± ± ± 2.80 Experimnetal group Upper right ± ± ± 4.47 Lower left ± ± ± ± ± ± 4.28 P-value * Values are mean ± SD Table 4. Fluorescence difference on maxilla at 4 weeks Group Name N ΔF(%)* Before treatment After treatment ΔΔF(%) Upper left ± ± ± 2.64 (Control group) Upper right ± ± ± 4.47 (Experimental group) P-value * Values are mean ± SD Table 5. Fluorescence difference on mandible at 4 weeks Group Name N ΔF(%)* Before treatment After treatment ΔΔF(%) Lower right ± ± ± 2.69 (Control group) Lower left ± ± ± 4.18 (Experimental group) P-value * Values are mean ± SD 87
6 Table 6. Fluorescence difference after reapplication on experimental group at 8 weeks Group Name N Before treatment ΔF(%)* After treatment (4 weeks) After treatment (8 weeks) Upper right ± ± ± 0.39 ΔΔF(%) ± ± 2.88 ΔΔΔF(%) ± 2.28 P-value * Values are mean ± SD ΔΔF(%) = After treatmnet ΔF(4 weeks, 8 weeks) - Before treatment ΔF ΔΔΔF(%) = ΔΔF(8 weeks) - ΔΔF(4 weeks) Table 7. Fluorescence difference after application on control group at 8 weeks Group Name N Before treatment ΔF(%)* After treatment (4 weeks) After treatment (8 weeks) Upper right ± ± ± 3.21 ΔΔF(%) ± ± 4.62 ΔΔΔF(%) ± 3.27 P-value * Values are mean ± SD ΔΔF(%) = After treatmnet ΔF(4 weeks, 8 weeks) - Before treatment ΔF ΔΔΔF(%) = ΔΔF(8 weeks) - ΔΔF(4 weeks) Figure 1. Quantitative light-induced fluorescence image on fluoride varnish reapplication group(upper right, #10). A = Baseline. B = 4 weeks. C = 8weeks. 88
7 Figure 2. Quantitative light-induced fluorescence image on fluoride application group after 4 weeks nature demineralization (lower right, #40). A = Baseline. B = 4 weeks. C = 8 weeks. Figure 3. Scanning electron micrograph of the teeth after fluoride application at 4 weeks. 1,000. A = Experimental group (lower left, #30). B = Control group (upper left, #20). Figure 4. Scanning electron micrograph of the teeth after fluoride application at 8 weeks. 1,000. C = Experimental group, fluoride varnish reapplication group after 4 weeks fluoride varnish application (upper right, #10). D = Control group, fluoride application group after 4 weeks nature demineralization (lower right, #40). 89
8 IV. DISCUSSION 본연구에서는일반적으로예방목적으로사용되는국소불소도포사용법중불소바니쉬의사용에의한법랑질탈회예방효과를 QLF와 SEM을통하여정량적, 정성적으로평가하였다. 초기치아우식병소의경우진행성우식으로이행되기전진단하는것이중요하고 (Ismail, 1997), 이러한치아우식증을관찰하기위한실험적방법으로, 편광현미경, 미세경도측정법, 주사레이저현미경등이사용되고있으나침습적인방법으로임상에서환자에게실제적으로적용하기는어렵다 (Ogaard 와 Rølla, 1992; Benson 등, 1999; Fontana 등, 1996). 따라서본연구에서사용한 QLF는전통적인검사방법보다비와동성우식및미세한병소도관찰이가능한장비로초기탐지능력이우수하며 (Kühnisch 등, 2007), Aljehani 등은교정장치가부착된치아주변의백색병소를정량화함에있어, QLF가다른우식탐지기기들보다더재현성이나정확성이뛰어난값을가진다고하였다. 또한 QLF는교정치료중인환자를비침습적으로측정할수있기때문에실제사람의구강내환경에서연구하는생체내 (in vivo) 연구에적합하게사용할수있었다. 생체내에서치질을 QLF로측정한형광량은수분의포함여부에따라빛의산란에영향을미쳐그값이달라지게되는데 (Ando 등, 2001), Ando 등 (2003) 의연구에따르면압축공기를통한건조시간이 3초이상되어야탈회된치질에서의자가형광성이뚜렷하게나타난다고하였다. 또한생체내실험의특성상측정과정에서다양한변수들이발생될수있으므로, QLF 측정후교정발치한해당치아들을 SEM 이미지촬영을통해보완적으로관찰하여, 정량적으로나온 QLF 데이터와비교해정성적인분석을추가하였다. 불소바니쉬는국소적으로적용하는불소도포방식중가장흔하게이용되는방식으로지각과민증의완화와치아우식증의예방및초기치아우식증진행억제등의효과가보고되고있다. 최근 Benson 등 (2013) 이발표한코크란리뷰에따르면일반치아및교정환자에게 6개월주기의불소바니쉬도포는초기백색병소의발생을 70% 가까이낮추는효과를가지고있으며, 미국의질병관리본부 (2001) 와미국치과의사협회 (2006) 의보고에의하면우식발생위험도가높은아동에게불소바니쉬를적용할경우우식예방효과가높은것으로나타났 다. Twetman 과 Peterson(1996) 은 4~5세아동에서불소바니쉬적용에따른우식발생억제효과를세계보건기구 (WHO) 의기준에따라연구하고불소바니쉬의우식정지효과를확인하였으며, 유치열및영구치열에서의불소바니쉬의우식정지효과및우식예방효과에관한많은연구들이진행되었고그효과가입증되었다 (ten Cate, 2013; Tufekci 등, 2011; Rogers 등, 2010). 불소바니쉬는다른불소제품에비해치아표면에부착이용이하고지속적으로불소를유리시켜항우식효과가뛰어난것으로알려져있으며, 환자의협조도에덜영향을받는것으로알려져있다 (Beltrán-Aguilar, 2000). 임상적으로권장되는불소바니쉬도포주기는미국 ADA와 CDC에서제안한최소 1년 2회이상 6개월주기로적어도 2년이상지속하는것을권장하며, 우식활성도가높은사람에게 3개월주기로적용하는것을권장하고있으나아직까지명백한적정도포주기와횟수가제시되어있지않다 (CDC, 2001; ADA, 2006). 본연구에서 QLF를이용한법랑질탈회량을살펴본결과 4주차에서대조군에서불소바니쉬를도포한실험군보다뚜렷하게형광량의소실이일어났으며, 이는불소바니쉬도포를통해교정환자에서치아우식증의예방효과가있다고결론지을수있다. 이는기존의진행된불소바니쉬의우식억제효과에관한임상연구들과같은양상을보이며 (Rechmann 등, 2013; Grover 등, 2012), 이러한정량적결과들을 SEM 이미지를통해정성적으로분석해본결과초기에불소바니쉬를도포한하악좌측소구치에서자연마모된경향성외에뚜렷한거친부분을확인할수없었지만대조군으로불소바니쉬를도포하지않은상악좌측의소구치같은경우 SEM 이미지상에서탈회된표면을확인할수있었다. 또한초기와 4주차에불소바니쉬를연속적으로재도포한상악우측의경우자연적인스크레치외의평활한면을확인할수있었으며, 초기에 4주간자연탈회시킨후 4주차에불소바니쉬를도포한하악우측소구치의경우재광화된구상형태의물질들을확인할수있었다. 불소바니쉬도포 4주후도포부위를상악, 하악으로층화하여분석해본결과상악에서의대조군과실험군의형광량변화는유의하지않은반면, 하악에서의형광량변화는대조군과실험군에서유의하게나타났다. 기존의 Wenderoth 등 (1999) 의연구에따르면상하악의탈회량은차이가발생하는데, 통 90
9 상적으로상악의전치부탈회량이하악전치부보다많으며, 부위별로는상악측절치와하악구치부에서가장많은탈회량을보이는것으로나타났다. 또한여러연구에서도전체적으로는상악이하악보다탈회량이크지만부위별로는상악전치부와하악구치부가탈회량이많으며 (Mizrahi, 1983; Mackay, 2005), 이는음식물의저류효과및여러가지요인에기인한다고하였다. 본연구에서도이러한상하악의기본적인탈회량의차이에기인하여본연구에서의상악과하악에서의형광량변화에영향을미친것으로사료된다. 불소바니쉬도포 8주후초기와 4주에반복적으로불소바니쉬를도포한상악우측부위에서탈회량이증가하는경향성을보였으나통계학적으로유의하지않았으며, 반면초기 4주간자연탈회후불소바니쉬를도포하여재광화효과를분석한하악우측부위의경우탈회량이줄어드는경향성을보였으나, 이또한통계학적으로유의하지않았다. 이는환자마다진행되는탈회정도와재광화정도가달라대상자들간의차이에대한통계적분석이용이하지않은한계점이있다. 하지만 4주간자연탈회후불소바니쉬를도포하여탈회량이줄어드는경향성을보인점은통상적으로 4주를주기로정기검진을진행하는교정치료환자들에서초기우식증발견시불소바니쉬의도포가우식증의진행을막는데도움이된다는임상적근거가될수있다고사료된다. 본연구에서는임상적한계로교정치료진행과정에영향을미치지않기위해치아의발거를진행할수밖에없었다. 이로인해 8주차에서각각상악, 하악의개별대조군이존재하지않으며, 통상적으로자연조건에서부위별, 환자별로탈회에대한민감도가달라직접적인비교를하기에한계가있었다. 따라서이러한한계점들을보완하여추후실험실내 (in vitro) 실험을통해정확한효과평가가연구되어야한다고사료되었다. V. CONCLUSIONS 교정환자에서불소바니쉬에의한예방효과를 QLF와 SEM 을이용하여확인해본결과 4주차에서대조군과실험군간의통계적으로유의한차이를볼수있었다. 대조군에서는초기에비해형광량이유의하게감소한반면불소바니쉬를도포한 실험군에서형광량소실이통계적으로유의하게나타나지않았다. 또한 SEM 이미지를통하여정성적으로분석해본결과표면상태가대조군에서탈회가일어나는양상을보였다. 따라서교정환자에서의불소바니쉬적용이초기우식증을예방할수있는효과적인방법이라할수있겠다. 또한 4주차에서자연탈회된치아와불소바니쉬를적용했던치아에불소바니쉬를적용한결과자연탈회된치아에형광량이다시회복되어재광화되는양상을보였으나통계적으로유의한차이를보이진않았다. SEM 이미지를통해정성적으로분석해본결과이미지상에재광화된입자들이나타났으나, 명확한대조군측정을위해 in vitro 에서의실험이추가적으로필요할것으로사료된다. Ⅵ. REFERENCES 1. Aljehani A, Tranaeus S, Forsberg CM, Angmar-Månsson B, Shi XQ (2004). In vitro quantification of white spot enamel lesions adjacent to fixed orthodontic appliances using quantitative light-induced fluorescence and DIAGNOdent. Acta Odontol Scand 62: American Dental Association Council on Scientific Affairs (2006). Professionally applied topical fluoride: evidence-based clinical recommendations. J Am Dent Assoc 137: Ando M, Schemehorn BR, Eckert GJ, Zero DT, Stookey GK (2003). Influence of enamel thickness on quantification of mineral loss in enamel using laser-induced fluorescence. Caries Res 37: Ando M, van Der Veen MH, Schemehorn BR, Stookey GK (2001). Comparative study to quantify demineralized enamel in deciduous and permanent teeth using laser- and light-induced fluorescence techniques. Caries Res 35: Angmar-Månsson B, ten Bosch JJ (2001). Quantitative light-induced fluorescence (QLF): a method for assessment of incipient caries lesions. Dentomaxillofac 91
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ABSTRACT QLF Concept and Clinical Implementation Department of Preventive Dentistry and Public Oral Health, College of Dentistry, Yonsei University Baek Il Kim, D.D.S., Ph.D. The leading paradigm of dentistry
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