- Email: [email protected]
The Prevention of Dental Caries: Ten Years Later
REVIEW H
ARTICLE
i
The prevention of dental caries: ten years later James P. Carlos, DDS
The program of the N ational Caries Program o f the N ational Institute o f D ental Research tow ard finding w ays to preven t caries on a w id esp rea d basis is assessed.
Ï
n 1971, S c h e rp 1 p u b lish ed a sem i nal p ap e r on th e p rospects for th e p re v en tio n of d en tal caries, in w h ich he su m m arized th e cu rre n t k n o w led g e of caries etiology an d speculated on the m ost p ro m isin g directio n s for futu re research. In th a t sam e year, th e N a tio n a l I n s titu te of D en tal R esearch b eg an th e N atio n al C aries Program . T his research and develo p m en t effort w as u n d erta k en for th e express p u r p o se of fin d in g cost-effective w ays to p re v e n t caries on a w id esp read basis, so th a t th is u b iq u ito u s disease could be e lim in a te d as a m ajor p u b lic h ealth problem . N ow , a d ecade later, it seem s a p p ro p riate to briefly assess th e extent to w h ic h p rogress has been m ade to w ard th a t goal. From th e outset, the N ational C aries P rogram has been organized into four areas of research strategy that follow d irec tly from th e con cep t th a t caries is of m u ltifa c to ria l etio lo g y . P ro g ram stra te g ie s in v o lv e fin d in g w ays to: co m b a t c a r ie s - in d u c in g m ic ro organism s; increase the resistan c e of th e teeth ; m odify caries-prom oting as pects of th e diet; a n d im prove delivery and ac ce p ta n ce of ca ries-p rev en tiv e m ethods. As th e im p o rta n ce of each of these strategies w as n o te d by S ch erp ,11 w ill ex am in e th e c u rren t state of d ev elo p
m e n t in ea ch . R eview p u b lic a tio n s w ill be cited w h erev er possible, as th e surge of in te rest in caries research d u r ing the last te n years is reflected in an ab u n d a n ce of relev an t n ew c o n trib u tio n s to th e scien tific literature.
C om bating caries-in d u cin g m icroorgan ism s In 1971, th e im p o rtan ce of S trep to co c c u s m u ta n s as a c a r ie s - in d u c in g p ath o g en in laboratory an im als had b ee n c le a rly e s ta b lish e d by e x p e ri m en ts w ith h am sters, rats, an d p ri m ates. T he ability of these b acteria to readily form p la q u e on sm ooth su r faces w as observed to be related , at least in part, to th e ir ability to p ro d u ce extracellular po ly sacch arid es (glucan a n d f r u c ta n ) fro m s u c ro s e . S o m e h o p ed th a t h u m a n d en tal caries could be p rev e n ted by th e u se of g lu can cleaving enzym es, su ch as dextranase; th is te ch n iq u e h ad been h ig h ly su c cessful in h am ste rs.2 U n fo rtu n a tely , th ese ex p e ctatio n s have n o t b een fulfilled. C linical trials of d extranase gels a p p lie d in m o u th p ie ce s r e s u lte d in little p ro te c tio n again st caries in c h ild re n ,3 no d oubt because of th e co m p lex ity of th e m a trix of h u m a n p la q u e relativ e to th a t in
ham sters, as w ell as to th e in ab ility to deliv er th e en zy m e w ith su fficien t fre quency. No o th er ag en t sp ecifically in te n d ed to su p p ress th e cario g en ic m icroflora h as yet rea ch ed th e stage of full-scale h u m a n te stin g in th is co u n try , b ut th e ac cu m u latio n of research k n o w ledg e about th e etio lo g ic role of bacteria in caries, an d , of co u rse, p o ssib le a n tib a c te r ia l in te r v e n tio n s , h a s p r o g ressed ex ten siv ely d u rin g th e past decade. T his is esp ecially w ell illu strated by im p ro v em en ts in o ur u n d e rsta n d in g of th e p ro cesses by w h ic h oral m icro o rg an ism s ad h e re to to o th surfaces. A l th o u g h rec en t research has confirm ed th a t su cro se-d eriv ed ex tracellu lar g lu can facilitates co lo n izatio n of sm ooth su rfa c e s by S m u t a n s , 4 w e h av e learn ed th a t other m ech an ism s in c lu d ing in terb acterial ag g reg atio n ,5 elec tro static attra c tio n ,6 sp ecific receptorty p e r e a c t i o n s , 7 th e p r e s e n c e of im m u n o g lo b u lin s in saliv a,5 an d m e ch an ical rete n tio n m ay also d eterm in e th e success or failu re of b acteria to ad h ere to teeth an d to o th er h u m an tissues. A p p re ciatio n of th e co m p lex ity of th e m icrobial etiology of d en tal caries w as fu rth e r ex ten d e d by th e rep o rt th at at least seven sero ty p es of S m u ta n s m ay b e iso lated from h u m an p la q u e,8 a l t h o u g h n o t all a p p e a r to be c a rio g en ic . In d e e d , c o n c lu siv e e v i d en ce is still lacking th a t S m u ta n s is th e p rim ary in itiato r of h u m a n caries, alth o u g h data acq u ired th u s far from b oth ep id em io lo g ic stu d ies an d a n i m al ex p e rim en ts are stro n g ly su g g es tive of th is.9 N evertheless, it has b e com e clear th a t o th er sp ecies of strepJADA, Vol. 104, February 1982 ■ 193
REVIEW
ARTICLE
Research to develop a caries vaccine has already stim ulated a m ajor expansion of know ledge about the secretory imm une system .
tococci, as w ell as of th e genera A ctin o m y cetes an d L actobacillus, are in volved in the caries process; n o t a ll of th em as pathogens, b u t certainly as co m p etitors for ecologic n ich es on the teeth. P relim inary experim ents w ith m ix ed oral flora suggest th a t th e even tu a l com position an d cariogenic p o te n tia l of plaq u e is in flu en ced n o t only by diet, b u t also by th e order in w h ich sp e c ific m ic ro o rg a n ism s a re in tr o d u c e d .10 It h as also b ee n established th a t m u ta n t form s of S m u ta n s th a t are deficient in th e ir ability to synthesize p o ly sa c c h a rid e from su g ar h av e r e d u c e d c a rio g e n ic p o te n tia l in a n i m a ls.11 T he develo p m en t of a “ safe” oral flora, w h ich co u ld successfully com pete w ith p ath o g en ic form s, th u s becom es a theoretical possibility. In h is 1971 p a p e r , S c h e r p 1 e x pressed th e prevailing view of sk e p ti cism th a t caries co u ld be prev en ted by im m u n iz a tio n , ev en th o u g h B ow en h a d already reported partial p ro tectio n ag ain st caries in m onkeys v accinated w ith S m u ta n s .12 Since then, reports from several la b o rato ries h av e co n firm ed th a t caries c a n be p artially p re v e n te d in m onkeys a n d ro d e n ts by v accin atio n w ith a variety of antigens; th e m o st co n sisten t success has been ach iev ed by intrao ral in jection w ith k illed cells of S m u tan s. E vidently, p ro tec tio n d ep en d s m a in ly on th e in d u ctio n o f elevated levels of salivary an tib o d y . T h ese s tu d ie s h av e b ee n su m m arized by B ow en.13 M ore recently, increased levels of bo th salivary a n d seru m a n tib o d ie s have been observed in h u m a n s w ho sw allo w ed capsules of k illed S m u ta n s c e lls , a n d th e a b ility of th e s e o r g anism s to colonize th e teeth of th e v a c c in a te d in d iv id u a ls w as sh a rp ly re d u c e d .14 T his is an extrem ely im p o r ta n t finding, b u t w e sh o u ld not co n c lu d e th a t a vaccine ag a in st h u m a n caries is im m inent. M uch research re m ain s to be d o n e to iden tify th e m ost p o te n t an tig en s an d th e optim al route an d frequency of vaccination, an d to establish th e safety of the p rocedure, before full-scale clin ical trials w ill be 194 ■ JADA, Vol. 104, February 1982
p o ssib le. (It is e n c o u rag in g th a t no notew orthy adverse effects have been rep o rted in th e h u n d re d s of an im als vaccinated so far.) E ven so, it can be now p red ic ted w ith som e co nfidence th a t p a rtia l p re v e n tio n , of caries by vaccination w ill becom e a reality. Re search to develop a caries v accine has already stim u la ted a m ajor ex p an sio n of know ledge ab o u t th e secretory im m u n e system , w ith b ro ad p o te n tia l a p p lic a b ility to o th e r are as of b io m edicine. M ore direct attem p ts to com bat th e cariogenic m icroflora h av e h a d less encouraging resu lts. A lth o u g h S cherp advocated “ a vig o ro u s p rogram to de velo p ra tio n a l u se of a n tim ic ro b ia l' agents to p ic ally ,” no su ch ag en ts have yet becom e av ailab le for g eneral use in caries preven tio n . T he p ro b lem is n o t p rim a rily a sc ie n tific one; th a t th e b is - b ig u a n id e , c h lo r h e x id in e , c a n p rev e n t p la q u e fo rm atio n an d caries has b een estab lish ed ,15 an d in o u r lab oratories, several an tim icro b ial agents h av e b ee n te s te d th a t a re e q u a l or su p erio r to ch lo rh e x id in e in in vitro a n d a n im a l c a rie s e x p e rim e n ts . R ather, progress h a s'b e e n reta rd e d by th e h ig h cost of th e req u ired to x icity testin g of a n ew d ru g before clin ic al trials can beg in , as w ell as th e as sociated problem s an d u n ce rtain ty of eventual reg u lato ry ap p ro v al. Efforts w ill co n tin u e to develop an tim icro b i als for use, for ex am p le, in m o u th rinses or den tifrices, b u t w e h av e a m ore realistic ap p re cia tio n of th e eco n o m ic an d re g u la to ry p ro b lem s in volved th a n w e h ad ten years ago.
Increasing the resistance of the teeth T he u se of flu o rid e in v ario u s form s co n tin u es to be th e m ost effective w ay to p re v e n t d en tal caries. C u rren tly , slig h tly m ore th a n h alf th e p o p u la tio n of th e U n ite d S tate s h a s a c ce ss to flu o rid a te d w ate r s u p p lie s b u t, b e cause m ost m etro p o litan areas h av e al ready ad o p ted flu o rid atio n , it is u n likely that th is fractio n w ill in crease
dram atically in th e im m ed iate future. E ven in o p tim ally flu o rid ated areas, it is desirable to attem p t to in crease th e level of p ro tec tio n ag ain st caries al read y attain ed . A s a con seq u en ce, flu o rid e re se a rc h d u rin g th e p a s t te n years has b een co n cen trated on th e d e v elo p m en t of m o re cost-effective w ays to d e liv e r d ie ta ry f lu o rid e s u p p le m en ts an d to p ical flu o rid es to com p le m e n t, a n d p o ssib ly su p p le m e n t, w ate r flu o rid a tio n . Som e m ajo r a d vances h av e resu lted . A d ecad e ago, it w as g en erally be lie v ed th a t th e flu o rid e io n m a in ly exerted its an ticaries effect by in c o rp o ra tio n in to e n a m e l as flu o ra p a tite , thereb y in creasin g th e resistan ce of th e to o th to ac id d isso lu tio n . S in ce th en , how ever, it h as becom e in creasin g ly ev id en t th a t other, p o ssib ly m ore im po rtan t, m e ch an ism s of flu o rid e action are o p era tiv e. E p id e m io lo g ic stu d y failed to d em o n strate co n siste n t corre latio n s b etw een caries p rev alen ce an d th e f lu o r id e c o n t e n t o f th e o u te r e n a m e l la y e r s .16 C o n v e rs e ly , v e ry sm all co n cen tratio n s of flu o rid e, co n tin u a lly p re se n t in th e m o u th , effec tiv ely p rev e n ted caries in rats, a n d th e level of p ro tec tio n w as n o t related to th e am o u n t of flu o rid e acq u ired by th e en am el.17 O th er ex p erim en ts sho w ed th a t lo w c o n c e n tra tio n s of flu o rid e w ere capable of rem in efalizin g in c i p ie n t carious le sio n s18 an d of in terfer in g w ith g ly c o ly tic a c t i v i t y a n d g ro w th of p la q u e b a c te ria .19 T h ese fin d in g s w ere in acco rd w ith rep o rts th a t caries in h u m a n s w as p artially p rev en ted b y freq u en t to p ical expo su re to lo w do ses of flu o rid e, even th o u g h in c re ase d levels of enam el flu orid e co u ld n o t be d etected .20 In th e aggregate, th is research re su lted in a ra th e r d rastic ch an g e in th e m eth o d s of to p ical flu o rid e therapy; rath e r th a n o ccasional ex p o su res of th e te eth to h ig h co n cen tratio n s of flu oride, it ap p e ared preferable to p ro v id e regular, freq u en t ex p o su re to rela tiv ely d ilu te flu o rid e so lu tio n s. T his w as confirm ed in a series of co n tro lled clin ical tria ls.21 C onsequently, th e N ational Caries Program began, in 1974, a series of d em o n stratio n program s n atio n w id e to te st th e feasibility, cost, a n d p u b lic acceptance of w eekly m o u th rin sin g in sc h o o ls w ith a n 0.2% s o lu tio n of so d iu m flu o rid e. T h e re s u lts estab lish ed th a t su c h pro g ram s w ere h ig h ly co st e ffe c tiv e .22 E stim a te s a re th a t
REVIEW
m o re th a n 13 m illio n s c h o o l-a g e d c h ild re n , m o stly in n o n flu o rid a te d a r e a s , a r e c u r r e n t l y e n r o l l e d in school-based flu o rid e rin se program s o r th e an alo g o u s p ro g ram s of d aily flu o rid e tab let ad m in istratio n . T hese ch ild ren can b e expected to average 30% to 40% few er n ew carious lesions at an an n u a l cost of as little as $0.50 per c h ild . R e ce n t re p o rts su g g e st th e se se lf-a p p lied flu o rid e p ro g ra m s m ay p ro v id e a d d e d p ro te c tio n in flu o ri d ated areas as w e ll.23 S h o u ld com m u n itie s c o n tin u e to a d o p t schoolb ased flu o rid e program s at th e p resen t rate, a m ajor im p act on th e incid en ce of c a rie s in c h ild r e n is in e v ita b le w ith in th e n ex t few years. T he d em o n
concern ab o u t th e u se of sealan ts w as d isp e lle d by th e d em o n stratio n th at, w h en sealan t w as p laced over active caries, th e lesio n s d id n o t progress an d te n d ed to becom e ste rile.27 It m u st be co n clu d ed th a t ad h esiv e se a la n ts affo rd a sim p le , safe, a n d h ig h ly effectiv e w ay to p ro te c t th e m o st v u ln e ra b le are as of th e te e th again st caries. W hy, th en , are sealan ts n o t m ore w id ely u se d in p u b lic h ea lth p rev e n tiv e p ro g ra m s? C ertain ly th e answ er involves th e cost of p rovision, as state law s restrict th e use of sealan ts to licensed d en tists or d en tal h ygienists. We h av e c a lc u la te d th a t, in a h y p o th etical p rev en tiv e program for s c h o o l c h i l d r e n , if s e a la n ts w e r e
Sealants are n ot w id ely used in pu blic health program s because o f cost; state la w s restrict the use of sealants to licen sed dentists or dental hygienists.
stratio n th a t fluoride a p p lie d d aily in gels co uld p rev e n t th e prev io u sly in tractable p roblem of extensive caries in p a tie n ts w h o se salivary fu n ctio n w as d estroyed by th e ra p eu tic irra d ia tio n 24 w as an o th er significant re su lt of recen t flu o rid e research. W e know , how ever, th a t flu o rid e is least effective in p rev e n tin g caries on th e o cclu sal surfaces of p o sterio r teeth. W h eth er th e se especially v ulnerable surfaces co u ld be p ro tected by sealing p its an d fissures w ith ad h esiv e p o ly m ers w as th e questio n stu d ied in a large series of clin ical trials th a t began in th e early 1970s. M ost stu d ies in v olved th e u se of an u ltra v io let lig h t p o ly m erized sealan t a p p lie d to enam el th a t h ad been etched w ith d ilu te acid. T he resu lts of som e of th ese stu d ies h a v e b e e n s u m m a r i z e d b y S ilv ersto n e.25 W ith careful atten tio n to th e te ch n iq u es of ap p licatio n , sealants co u ld be reta in ed in m ore th an h a lf th e treated sites for m ore th a n five years, w ith n e a r c o m p le te p r e v e n tio n of caries.26 P rotection of th e etch ed su r face from salivary co n tam in atio n w as fo u n d to be critical to successful se al a n t a p p lic a tio n , as e tc h e d surfaces w ere ra p id ly rem in eralized on contact w ith o ral flu id s. M ore re c e n t tria ls w ith ch em ically p olym erized sealants h av e also been h ig h ly successful in prev en tin g occlu sal caries.26 O ne early
ap p lied once a year to all n o n cario u s occlusal surfaces, th e cost of p rev e n t ing a single cavity co u ld ran g e from $15 to $26, d e p e n d in g on th e in h e re n t caries su sc ep tib ility of th e p o p u la tio n trea ted . It is im p ro b a b le th a t m an y c o m m u n itie s w ill a d o p t su c h p r o gram s. U n til ad h esiv e sealan ts can be legally a p p lie d by less h ig h ly train ed auxiliaries, th e ir fu ll effectiveness in ca ries p re v e n tio n is u n lik e ly to be realized. N evertheless, th e u se of seal ants is n o w reco m m en d ed in d en tal offices a n d c lin ic s, w h e re re q u ire d p erso n n e l are alread y in place. T opical flu o rid es an d sealan ts are ex te rn a lly a p p lie d p re v e n tiv e te c h n iq u es in te n d e d to in crease th e resist ance of te eth to caries. N atural host defense m ech an ism s m ay also b e o p erative in th e m o u th , a p o ssib ility th at h as receiv ed in creased atte n tio n re cen tly w ith p ro m isin g results. Efforts to prev en t caries by stim u la tio n of th e im m u n e sy ste m h av e a lre a d y b een m entioned. A lso of p o ten tial sig n ifi ca n ce are th e n o n im m u n o lo g ic a n tib acterial co m p o n en ts of saliv a in c lu d in g ly so z y m e , la c to fe rrin , lactoperoxidase, an d other salivary p ro te in s th a t m ay be b acteriacid al o r m ay regulate th e ecology of p laq u e an d the clearance of bacteria from th e m o u th .28 T his is a relativ ely n ew area of in te n sive research. W h eth er th ese factors
ARTICLE
have a key ro le in caries p rev en tio n an d , if so, w h eth e r it is p o ssib le to m a n ip u la te th e ir co n cen tratio n a n d activ ity in saliva are q u estio n s being in v es tigated.
Modifying the diet O f th e research efforts to effectively in terv en e in th e etiologic triad of d e n tal caries, th o se d irected at alterin g d ietary factors have so far m et w ith th e least success. G iven th e p ro cliv ity of a large seg m en t of th e p o p u la tio n , a n d especially of ch ild ren , for sw eet foods, it seem s fu tile to striv e for m ajor changes in d ietary habits, even th o u g h there is co m p ellin g ev id en ce th a t a sharp re d u ctio n in th e a m o u n t,29 or even in th e fre q u e n c y ,30 of su g a rs ea te n w o u ld have a salu tary im p act on caries prev a le n ce . In ste a d , re c e n t re se a rc h h as been d irec ted to id en tify in g an d d e v e lo p in g s u b s ta n c e s th a t m ig h t be a d d e d to s u g a rs to d e c re a s e th e ir cariogenicity, or th a t co u ld serve as ta s te - c o m p e t itiv e , n o n c a r io g e n ic sugar substitutes. In 1971, v a rio u s p h o s p h a te co m p o u n d s ap p eared esp ecially p ro m is ing. In m ore th a n 100 ex p erim en ts on an im als, p h o sp h a te s ad d e d to food a n d d rin k in g w ate r h a d effectiv ely p r e v e n te d m o s t c a r ie s .1 H o w ev er, m ost su b seq u en t trials in h u m an s in w h ich d ic alc iu m or d ih y d ro g en p h o s p h a te s w ere a d d e d to flo u r, b read , su g ar, ch e w in g g u m , an d breakfast cereals en d e d w ith eq uivocal results, alth o u g h th e p h o sp h a te ad d itiv e a p p eared to red u c e th e cario g en ic p o te n tia l o f c h e w in g g u m .31 S im ila rly , so d iu m trim e tap h o sp h ate , w h ich h ad been th e m ost effective co m p o u n d of those stu d ied in anim als, failed to p re v en t caries to an y sig n ifican t degree w h en given in ch ew in g gum to c h il d re n .32 It is likely th ese d isa p p o in tin g resu lts can be ex p lain ed by the fact that, in ex p erim en ts w ith anim als, th e p h o sp h a te co m p o u n d s w ere p resen t in all food a n d w ater c o n s u m e d , w h erea s, in ex p erim en ts w ith h u m an s, only in term itten t, an d p robably inad eq u ate, ex p o su re to th e co m p o u n d s w as ac c o m p lish e d . E ven so, th e id e a of a sugar ad d itiv e th a t w o u ld prev en t or atten u a te th e effect of acid p ro d u ctio n in p laq u e rem ain s an attractiv e one; p re su m a b ly th e u se of su c h a su b s ta n c e w o u ld r e q u ir e lit t l e o r n o ch an g e in food tech n o lo g y or personal Carlos : PREVENTION OF DENTAL CARIES ■ 195
REVIEW
ARTICLE
habits. T h is is an area of investigation th a t d eserv es ren e w e d a tte n tio n by b o th caries researchers and th e food in d u stry. T en years ago, it w as also th o u g h t th a t g lu cose an d fructose m ig h t be less c a rio g e n ic s u b s titu te s fo r su c ro se . T h is w as n o t su b sta n tia te d by su b se q u e n t re se a rc h in a n im a ls ,33 b u t m a n y o th e r p o s s ib ilitie s ex ist. F or exam ple, w h en young a d u lts ate diets in w h ic h all ad d ed sugars h ad been su b stitu te d by th e polyol xylitol, v ir tu a lly no caries occurred d u rin g th e 25-m onth study, in contrast to su b s ta n tia l le v e ls of c a rie s in c id e n c e am ong g roups eating diets sw eetened w ith su c ro se or g lu c o se .29 B ecause som e q u estio n s have been raise d co n cern in g its safety, xylitol is n o t yet available in th e U nited States, b u t it is w id ely u se d in confections in som e E u ro p ean countries. Of th e m any sy n th etic sw eeteners th a t h ave been identified, th e d ip e p tid e asp artam e cu rren tly appears m ost p ro m isin g as a n oncariogenic sugar su b stitu te, especially in dry foods.34 T h is c o m p o u n d is u n d e r review by th e F ood a n d D rug A d m inistration. O ther p o te n tia l ca n d id a tes of natu ral origin in c lu d e T h au m atin , a sw eet protein, a n d g ly cy rrh izin , a salt of an acid from lico rice root. Each of th e sugar su b sti tu te s c u rren tly u n d e r stu d y has one or m o re shortcom ings, such as h ig h cost or p o o r so lu b ility or therm olability, th a t w o u ld lim it its u se to certain types o f sn ack foods. T herefore, w e m ay ex p e c t a v ariety of n ew sw eeteners to ev e n tu a lly be m arketed. E ven w h e n su ita b le su g ar su b sti tu te s becom e available, it w ill n o t be feasible or d esirable to su b stitu te th em for all ad d e d sugars. Rather, it w ill be n ecessary to id en tify th o se foods that c o n t r i b u t e m o s t h e a v i l y to t h e cario g enic p o te n tia l of th e A m erican d ie t an d th a t sh o u ld therefore be given p rio rity for reform ulation. U n til re cen tly , little research data existed on th e c a rio g e n ic p o te n tia l of sp e cific com m on food item s. B ecause ethical co n sid eratio n s p rec lu d e th e ev a lu a tio n of th e cariogenicity of foods by c o n v en tio n al clin ical trials, several a t te m p ts h a v e b e e n m a d e to d e v is e screen ing system s based on in vitro, an im al, or short-term h u m a n ex p e ri m ents. T he m ost prom isin g system s rep o rted so far involve the m easu re m e n t of acid p ro d u ctio n in plaq u e in situ w h ile h u m a n volu n teers eat the 196 ■ JADA, Vol. 104, February 1982
te st foods,35 an d a h ig h ly co n tro lled a n d re p ro d u cib le rat-feeding system dev elo p ed in th e N ational Caries P ro gram laborato ries.36 T he latter te c h n iq u e p ro d u ce d data th a t can be u se d to a s s i g n to e a c h f o o d t e s t e d a “ cariogenic p o te n tia l in d e x ,” relativ e to th a t of p u re sucrose. A co m b in atio n o f th e se m e th o d s co u ld be u s e d to b e g in to d e v e lo p d a ta to id e n tif y d ietary co n stitu e n ts of greatest in te rest for caries p rev en tio n .
Improving delivery and acceptance of cariespreventive methods P rogram s to p rev e n t d e n ta l caries m u st co m p ete for in c re asin g ly scarce r e sources w ith other h ealth , p erso n al, a n d s o c ie ta l n e e d s. U n fo rtu n a te ly , d e n ta l h e a lth is ra re ly g iv e n h ig h p rio rity in su c h situ atio n s. T herefore, it is n o longer sufficient to search for caries-preventiv e m eth o d s th a t h av e a h ig h deg ree of b io lo g ic efficacy; to have any substan tial im p act on caries prevalence, p rev en tiv e m e th o d s m u st
d en tly su ch program s are rea d ily ac cep ted in b oth u rb an an d ru ral set tings. (A cceptance h as been su b stan tia lly lo w e r am o n g o ld e r c h ild re n . H ow th is gro u p can be m ore su ccess fu lly m o tiv ated is a research q u estio n th a t needs an early solution.) T h e low co st of self-ap p lied flu o rid e pro g ram s a ris e s fro m th e fac t th a t a d e q u a te su p e rv isio n can be p ro v id ed by class room teach ers or ad u lt v o lu n teers after very brief train in g . In d ee d , im p ro v in g th e cost-effectiv e n e s s o f te c h n iq u e s to p r e v e n t caries alm o st alw ays involves fin d in g w ays to red u c e th e cost of p rovision; few p rev e n tiv e m ethods, eith er av a il able or an ticip ate d , are in h e re n tly ex pen siv e. In general, m eth o d s th a t re q u ire freq u en t, one-on-one co n tact b e tw e e n th e r e c ip ie n t a n d a h ig h ly train ed p ro v id er w ill te n d to h av e poor cost-effective characteristics, as is cu r re n tly th e case w ith adh esiv e sealants. In th is reg ard , recen t research on th e ad a p ta tio n of co ntrolled, slow -release d eliv ery tech n o lo g y for in trao ral u se h as p ro d u c e d som e en co u rag in g re sults. T h e ratio n ale for slow -release
Each o f the sugar substitutes n ow under study has one or m ore shortcomings, such as high cost or poor solubility, that w ou ld lim it its use to certain types o f snack foods.
also be deliverab le to large segm ents of th e p o p u la tio n , at low cost and, p ro b a bly, w ith m in im al req u irem en ts for p o sitiv e actio n o n th e p a rt of th e in te n d e d recip ien ts. C om m unity w ater flu o rid atio n rem ain s th e arch ety p ical exam ple of a p rev en tiv e p ro g ram th a t satisfies th e se criteria, b u t other a ttra c tiv e p o ssib ilities for im proved d eliv ery system s h av e em erged d u rin g th e p ast several years. School-based, self-applied flu o rid e program s offer an in ex p en siv e w ay to pro v id e p artial p rev en tio n of caries to large n u m b ers of ch ild ren , in te rfe r in g only m in im ally w ith n o rm al ac tivities. In a series of co m m u n ity d em o n s tr a tio n s of th is te c h n iq u e c o n d u c te d b y th e N atio n al C aries P ro g ra m , m o re th a n 80% of e l ig ib le elem e n ta ry sch o o l c h ild re n p a rtic i p a te d , w ith p a re n ta l c o n s e n t; e v i
system s rests on th e assu m p tio n th a t sm all co n cen tratio n s of an active ag en t ca n p ro d u ce a th e ra p eu tic resu lt, if th e ag en t is co n stan tly p resen t at th e ta rg et site. O f equal im p o rtan ce, slow -release c h e m o th e ra p y re q u ire s o n ly o c c a sio n al co n tact w ith th e p atien t, th u s red u c in g p ro v isio n costs. A t p r e s e n t, th e m o st d e v e lo p e d slow -release system for caries p rev e n tio n is a flu o rid e -c o n ta in in g , in e rt p o ly m er d ev ice th a t can be te m p o rar ily attac h ed to p artial d en tu re s, or th o d o n tic ap p lian ces, or d irectly to a tooth. In tests w ith h u m a n volu n teers, th ese dev ices w ere w ell to lerated an d fu n ctio n ed w ith satisfactory precisio n . T h ey h av e been fabricated to release co n stan t, p red e term in e d rates of flu o rid e for u p to six m onths, an d sh o u ld be su itab le for th e d elivery of o th er an ticaries ag en ts as w ell.37
REVIEW
E v en th e m o st c o s t-e ffe c tiv e m e th o d s to p rev e n t caries w ill n o t be u se d u n le ss th e in te n d e d rec ip ien ts are aw are of th e po ten tial benefits an d seek o r ac ce p t th e req u ired regim en. Efforts to im prove th e p u b lic ’s u n d e r sta n d in g of th e causes a n d p rev en tio n of caries h ave certainly increased d u r ing rec en t years, b u t m u c h rem ains to be done. F or exam ple, there is no ap p a re n t reason except lack of k n o w l ed g e w h y all scho o lch ild ren , or at least th o se in n o n flu o rid ate d com m unities, s h o u ld n o t be p a rticip a tin g in self a p p lie d program s. T his is a short-term goal th a t is w o rth a concentrated e d u catio n al effort by th e en tire d ental p ro fession.
Conclusions By an y s ta n d a rd s, p ro g re ss to w a rd caries p rev e n tio n has been im pressive d u rin g th e p ast decade. It is arguable th a t m ore inform ation on th e precise etiology of caries an d on p o ten tial n ew p rev en tiv e m eth o d s has been acquired d u rin g th e 1970s th a n in an y com para b le p erio d previously. S u bstantial ad v an ces h ave b een m ad e to w ard th e u n d e rsta n d in g of th e com plex in te rac tio n am ong oral m icroorganism s, h o st resistan ce, an d dietary substrate in th e in itiatio n a n d progression of a caries lesion. T he various m echanism s of ac tio n of th e flu o rid e io n h av e b e e n fu rth e r elu cid ated ; vaccin atio n again st c a r ie s a n d a r e d u c tio n in th e ca rio g en ic p o te n tia l of sw ee t foods h a v e b o th b e c o m e r e a l i s t i c p o s sibilities. C o n s p ic u o u s su c ce sses h av e also b een ach iev ed in th e ap p lica tio n of ex istin g k now ledge. A t least 12 m il lio n m ore ch ild re n th an in 1971 are re c e iv in g p a rtia l p ro te c tio n a g a in st caries th ro u g h se lf-a p p lied flu o rid e program s. O ther effective p reventive m eth o d s, in c lu d in g adhesive sealants an d , p o ssibly, an tim icro b ial agents, co u ld be w id ely an d advantageously u tiliz e d if m an p o w er an d reg ulatory co n stra in ts w ere overcom e, as th e ir scien tific feasibility has, for th e m ost part, alre ad y been dem onstrated. Of course, it w o u ld be naive to p re d ic t th e early d isap p earan ce of dental caries as a m ajor h ealth problem . T h is w ill o ccur on ly gradually, an d w ill re
q u ire a m u c h m ore ex ten siv e u se of p re v e n tiv e m e th o d s— th o se a lre a d y available as w ell as th o se still b eing d eveloped by research. N evertheless, a m ajor step tow ard th e goal of caries p re v e n tio n h as a lre ad y b een tak en , an d th ere is good reaso n to expect even m ore rap id progress d u rin g th e 1980s.
Dr. Carlos is director, National Caries Program, National Institute of Dental Research, National Institutes of Health, Bethesda, Md 20205. Re quests for reprints should be sent to the author. 1. Scherp, H.W. Dental caries: prospects for prevention. Science 173:1199-1205, 1971. 2. Fitzgerald, R.J., and others. The effects of a dextranase preparation on plaque and caries in hamsters, a preliminary report. JADA 76:301-304, 1968. 3. Duany, L.F., and others. Effect of dextranase on oral health in children. J Prev Dent 2(2):23-27, 1975. 4. Gibbons, R.J., and Van Houte, J. Bacterial adherence in oral microbial ecology. Ann Rev Microbiol 29:19-44, 1975. 5. Van Houte, J. Oral bacterial colonization: mechanisms and implications. Microbial Abstr (suppl vol IJ:3-32, 1976. 6. Rolla, G,; Bonesvoll, P.; and Opermann, R. Interactions between oral streptococci and sali vary proteins. Microbiol Abstr (supp vol II):227241, 1979. 7. Gibbons, R.J. On the mechanism of bacterial attachment to teeth. Microbiol Abstr (suppl vol I):267-273, 1979. 8. Bratthall, D., and Kohler, B. Streptococcus mutans serotypes: some aspects of their identifi cation, distribution, antigenic shifts and relation ship to caries. J Dent Res 55 (special issue C):C15-21, 1976. 9. Hardie, J.M., and Bowden, G.H. The micro bial flora of dental plaque: bacterial succession and isolation considerations. Microbiol Abstr (suppl vol I):63-87, 1976. 10. Mikx, F., and others. Effect of Actinomyces viscosus on the establishment and symbiosis of Streptococcus mutans and Streptococcus sanguis in SPF rats on different sucrose diets. Caries Res 9:1-20, 1975. 11. Tanzer, J.M., and others. Diminished viru lence of glucan-synthesis defective mutants of Streptococcus mutans. Infect Immun 10:197-203, 1974. 12. Bowen, W.H. A vaccine against dental caries: a pilot study in monkeys. Br Dent J 126:159-160, 1969. 13. Bowen, W.H. Relevance of caries vaccine investigations in rodents, primates and humans: critical assessm ent. Im m un Abstr (special suppl):ll-20, 1976. 14. McGhee, J.R.; Mestecky, J.; and Arnold, R.R. Induction of secretory antibodies in humans following ingestion of Streptococcus mutans. Adv Exp Biol 107:177-184, 1978. 15. Loe, H.; von derFehr, F.R.,and Shiott, C.R. Inhibition of experimental caries by plaque pre vention. Scand J Dent Res 80:1-9, 1972.
ARTICLE
16. DePaola, P.F., and others. A pilot study of the relationship between caries experience and surface enamel fluoride in man. Arch Oral Biol 20(12):859-864, 1975. 17. Larson, R.H., and others. Caries inhibition in the rat by water-borne and enamel-borne fluo ride. Caries Res 10:321-331, 1976. 18. S ilv ersto n e , L.M. R em in eralizatio n phenomena. Caries Res 11 (suppl l):59-74,1977. 19. Hamilton, I.R. Effects of fluoride on en zymatic regulation of bacterial carbohydrate metabolism. Caries Res ll(su p p l l):262-278, 1977. 20. Shern, R.; Driscoll, W.; and Korts, D. Enamel biopsy results of children receiving fluo ride tablets. JADA 95:310-315, 1977. 21. Horowitz, H.S. The prevention of dental caries by mouthrinsing with solutions of neutral sodium fluoride. Int Dent J 23:585-590, 1973. 22. Miller, A.J., and Brunelle, J.A. Fluoride rinses. In Stewart, R.D., and others. Pediatric den tistry: scientific foundations and clinical practice. St. Louis, C. V. Mosby Co, 1982. 2 3 ..D risco ll, W .S., and o th ers. C ariespreventive effects of daily and weekly fluoride mouthrinsing in a fluoridated community.J Dent Res 60 (special issue A), abstr no. 647, 1981. 24. Dreizen, S., and others. Prevention of xerostomia-related dental caries in irradiated cancer patients. J Dent Res 56(1):99-104, 1977. 25. Silverstone, L.M. Preventive dentistry. London, Update Books, 1978, p 97. 26. Horowitz, H.S.; Heifetz, S.B.; and Poulsen, S. Retention and effectiveness of a single applica tion of an adhesive sealant in preventing occlusal caries: final report after five years of a study in Kalispell, Montana. JADA 95:1133-1139, 1977. 27. Handelmann, S.L.; Buonocore, M.G.; and Schoute, P.C. Progress report on the effect of a fissure sealant on bacteria in dental caries. JADA 87:1189-1191, 1973. 28. Mandel, I.D. Salivary factors in caries pre diction. Microbiol Abstr (suppl):147-158, 1978. 29. Scheinen, A., and Makinen, K.K. The Turku sugar studies I-XXI. Acta Odontol Scand 32:383-412, 1974. 30. Gustafsson, B.E., and others. The Vipeholm dental caries study. The effect of different levels of carbohydrate intake on caries activity in 436 individuals observed for five years. Acta Odontol Scand 11:232-364, 1954. 31. Mandel, I.D. Effect of dietary modifications on caries in humans. J Dent Res 49(suppl):12011211,1970. 32. Finn, S.B., and others. The effect of sodium trimetaphosphate (TMP) as a chewing gum addi tive on caries increments in children. JADA 96:651-655, 1978. 33. Bowen, W.H. Role of carbohydrates in den tal caries. Feeding, weight and obesity abstr (spe cial suppl):147-152, 1978. 34. Bost, R.G., and Ripper, A. Aspartame: a com m ercially feasible aspartic acid based sweetener. Feeding, weight and obesity abstr (special suppl}:269-281, 1978. 35. Muhlemann, H.R. Intra-oral radio tele metry. Int Dent J 21:456-461, 1971. 36. Bowen, W.H., and others. A method to as sess cariogenic potential of foodstuffs. JADA 100:677-681, 1980. 3 7 . M ir th , D .B ., a n d B o w e n , W .H . Chemotherapy: antimicrobials and methods of delivery. Microbial Abstr (suppl vol I):249-262, 1976.
Carlos : PREVENTION OF DENTAL CARIES « 1 9 7
ARTICLE
i
The prevention of dental caries: ten years later James P. Carlos, DDS
The program of the N ational Caries Program o f the N ational Institute o f D ental Research tow ard finding w ays to preven t caries on a w id esp rea d basis is assessed.
Ï
n 1971, S c h e rp 1 p u b lish ed a sem i nal p ap e r on th e p rospects for th e p re v en tio n of d en tal caries, in w h ich he su m m arized th e cu rre n t k n o w led g e of caries etiology an d speculated on the m ost p ro m isin g directio n s for futu re research. In th a t sam e year, th e N a tio n a l I n s titu te of D en tal R esearch b eg an th e N atio n al C aries Program . T his research and develo p m en t effort w as u n d erta k en for th e express p u r p o se of fin d in g cost-effective w ays to p re v e n t caries on a w id esp read basis, so th a t th is u b iq u ito u s disease could be e lim in a te d as a m ajor p u b lic h ealth problem . N ow , a d ecade later, it seem s a p p ro p riate to briefly assess th e extent to w h ic h p rogress has been m ade to w ard th a t goal. From th e outset, the N ational C aries P rogram has been organized into four areas of research strategy that follow d irec tly from th e con cep t th a t caries is of m u ltifa c to ria l etio lo g y . P ro g ram stra te g ie s in v o lv e fin d in g w ays to: co m b a t c a r ie s - in d u c in g m ic ro organism s; increase the resistan c e of th e teeth ; m odify caries-prom oting as pects of th e diet; a n d im prove delivery and ac ce p ta n ce of ca ries-p rev en tiv e m ethods. As th e im p o rta n ce of each of these strategies w as n o te d by S ch erp ,11 w ill ex am in e th e c u rren t state of d ev elo p
m e n t in ea ch . R eview p u b lic a tio n s w ill be cited w h erev er possible, as th e surge of in te rest in caries research d u r ing the last te n years is reflected in an ab u n d a n ce of relev an t n ew c o n trib u tio n s to th e scien tific literature.
C om bating caries-in d u cin g m icroorgan ism s In 1971, th e im p o rtan ce of S trep to co c c u s m u ta n s as a c a r ie s - in d u c in g p ath o g en in laboratory an im als had b ee n c le a rly e s ta b lish e d by e x p e ri m en ts w ith h am sters, rats, an d p ri m ates. T he ability of these b acteria to readily form p la q u e on sm ooth su r faces w as observed to be related , at least in part, to th e ir ability to p ro d u ce extracellular po ly sacch arid es (glucan a n d f r u c ta n ) fro m s u c ro s e . S o m e h o p ed th a t h u m a n d en tal caries could be p rev e n ted by th e u se of g lu can cleaving enzym es, su ch as dextranase; th is te ch n iq u e h ad been h ig h ly su c cessful in h am ste rs.2 U n fo rtu n a tely , th ese ex p e ctatio n s have n o t b een fulfilled. C linical trials of d extranase gels a p p lie d in m o u th p ie ce s r e s u lte d in little p ro te c tio n again st caries in c h ild re n ,3 no d oubt because of th e co m p lex ity of th e m a trix of h u m a n p la q u e relativ e to th a t in
ham sters, as w ell as to th e in ab ility to deliv er th e en zy m e w ith su fficien t fre quency. No o th er ag en t sp ecifically in te n d ed to su p p ress th e cario g en ic m icroflora h as yet rea ch ed th e stage of full-scale h u m a n te stin g in th is co u n try , b ut th e ac cu m u latio n of research k n o w ledg e about th e etio lo g ic role of bacteria in caries, an d , of co u rse, p o ssib le a n tib a c te r ia l in te r v e n tio n s , h a s p r o g ressed ex ten siv ely d u rin g th e past decade. T his is esp ecially w ell illu strated by im p ro v em en ts in o ur u n d e rsta n d in g of th e p ro cesses by w h ic h oral m icro o rg an ism s ad h e re to to o th surfaces. A l th o u g h rec en t research has confirm ed th a t su cro se-d eriv ed ex tracellu lar g lu can facilitates co lo n izatio n of sm ooth su rfa c e s by S m u t a n s , 4 w e h av e learn ed th a t other m ech an ism s in c lu d ing in terb acterial ag g reg atio n ,5 elec tro static attra c tio n ,6 sp ecific receptorty p e r e a c t i o n s , 7 th e p r e s e n c e of im m u n o g lo b u lin s in saliv a,5 an d m e ch an ical rete n tio n m ay also d eterm in e th e success or failu re of b acteria to ad h ere to teeth an d to o th er h u m an tissues. A p p re ciatio n of th e co m p lex ity of th e m icrobial etiology of d en tal caries w as fu rth e r ex ten d e d by th e rep o rt th at at least seven sero ty p es of S m u ta n s m ay b e iso lated from h u m an p la q u e,8 a l t h o u g h n o t all a p p e a r to be c a rio g en ic . In d e e d , c o n c lu siv e e v i d en ce is still lacking th a t S m u ta n s is th e p rim ary in itiato r of h u m a n caries, alth o u g h data acq u ired th u s far from b oth ep id em io lo g ic stu d ies an d a n i m al ex p e rim en ts are stro n g ly su g g es tive of th is.9 N evertheless, it has b e com e clear th a t o th er sp ecies of strepJADA, Vol. 104, February 1982 ■ 193
REVIEW
ARTICLE
Research to develop a caries vaccine has already stim ulated a m ajor expansion of know ledge about the secretory imm une system .
tococci, as w ell as of th e genera A ctin o m y cetes an d L actobacillus, are in volved in the caries process; n o t a ll of th em as pathogens, b u t certainly as co m p etitors for ecologic n ich es on the teeth. P relim inary experim ents w ith m ix ed oral flora suggest th a t th e even tu a l com position an d cariogenic p o te n tia l of plaq u e is in flu en ced n o t only by diet, b u t also by th e order in w h ich sp e c ific m ic ro o rg a n ism s a re in tr o d u c e d .10 It h as also b ee n established th a t m u ta n t form s of S m u ta n s th a t are deficient in th e ir ability to synthesize p o ly sa c c h a rid e from su g ar h av e r e d u c e d c a rio g e n ic p o te n tia l in a n i m a ls.11 T he develo p m en t of a “ safe” oral flora, w h ich co u ld successfully com pete w ith p ath o g en ic form s, th u s becom es a theoretical possibility. In h is 1971 p a p e r , S c h e r p 1 e x pressed th e prevailing view of sk e p ti cism th a t caries co u ld be prev en ted by im m u n iz a tio n , ev en th o u g h B ow en h a d already reported partial p ro tectio n ag ain st caries in m onkeys v accinated w ith S m u ta n s .12 Since then, reports from several la b o rato ries h av e co n firm ed th a t caries c a n be p artially p re v e n te d in m onkeys a n d ro d e n ts by v accin atio n w ith a variety of antigens; th e m o st co n sisten t success has been ach iev ed by intrao ral in jection w ith k illed cells of S m u tan s. E vidently, p ro tec tio n d ep en d s m a in ly on th e in d u ctio n o f elevated levels of salivary an tib o d y . T h ese s tu d ie s h av e b ee n su m m arized by B ow en.13 M ore recently, increased levels of bo th salivary a n d seru m a n tib o d ie s have been observed in h u m a n s w ho sw allo w ed capsules of k illed S m u ta n s c e lls , a n d th e a b ility of th e s e o r g anism s to colonize th e teeth of th e v a c c in a te d in d iv id u a ls w as sh a rp ly re d u c e d .14 T his is an extrem ely im p o r ta n t finding, b u t w e sh o u ld not co n c lu d e th a t a vaccine ag a in st h u m a n caries is im m inent. M uch research re m ain s to be d o n e to iden tify th e m ost p o te n t an tig en s an d th e optim al route an d frequency of vaccination, an d to establish th e safety of the p rocedure, before full-scale clin ical trials w ill be 194 ■ JADA, Vol. 104, February 1982
p o ssib le. (It is e n c o u rag in g th a t no notew orthy adverse effects have been rep o rted in th e h u n d re d s of an im als vaccinated so far.) E ven so, it can be now p red ic ted w ith som e co nfidence th a t p a rtia l p re v e n tio n , of caries by vaccination w ill becom e a reality. Re search to develop a caries v accine has already stim u la ted a m ajor ex p an sio n of know ledge ab o u t th e secretory im m u n e system , w ith b ro ad p o te n tia l a p p lic a b ility to o th e r are as of b io m edicine. M ore direct attem p ts to com bat th e cariogenic m icroflora h av e h a d less encouraging resu lts. A lth o u g h S cherp advocated “ a vig o ro u s p rogram to de velo p ra tio n a l u se of a n tim ic ro b ia l' agents to p ic ally ,” no su ch ag en ts have yet becom e av ailab le for g eneral use in caries preven tio n . T he p ro b lem is n o t p rim a rily a sc ie n tific one; th a t th e b is - b ig u a n id e , c h lo r h e x id in e , c a n p rev e n t p la q u e fo rm atio n an d caries has b een estab lish ed ,15 an d in o u r lab oratories, several an tim icro b ial agents h av e b ee n te s te d th a t a re e q u a l or su p erio r to ch lo rh e x id in e in in vitro a n d a n im a l c a rie s e x p e rim e n ts . R ather, progress h a s'b e e n reta rd e d by th e h ig h cost of th e req u ired to x icity testin g of a n ew d ru g before clin ic al trials can beg in , as w ell as th e as sociated problem s an d u n ce rtain ty of eventual reg u lato ry ap p ro v al. Efforts w ill co n tin u e to develop an tim icro b i als for use, for ex am p le, in m o u th rinses or den tifrices, b u t w e h av e a m ore realistic ap p re cia tio n of th e eco n o m ic an d re g u la to ry p ro b lem s in volved th a n w e h ad ten years ago.
Increasing the resistance of the teeth T he u se of flu o rid e in v ario u s form s co n tin u es to be th e m ost effective w ay to p re v e n t d en tal caries. C u rren tly , slig h tly m ore th a n h alf th e p o p u la tio n of th e U n ite d S tate s h a s a c ce ss to flu o rid a te d w ate r s u p p lie s b u t, b e cause m ost m etro p o litan areas h av e al ready ad o p ted flu o rid atio n , it is u n likely that th is fractio n w ill in crease
dram atically in th e im m ed iate future. E ven in o p tim ally flu o rid ated areas, it is desirable to attem p t to in crease th e level of p ro tec tio n ag ain st caries al read y attain ed . A s a con seq u en ce, flu o rid e re se a rc h d u rin g th e p a s t te n years has b een co n cen trated on th e d e v elo p m en t of m o re cost-effective w ays to d e liv e r d ie ta ry f lu o rid e s u p p le m en ts an d to p ical flu o rid es to com p le m e n t, a n d p o ssib ly su p p le m e n t, w ate r flu o rid a tio n . Som e m ajo r a d vances h av e resu lted . A d ecad e ago, it w as g en erally be lie v ed th a t th e flu o rid e io n m a in ly exerted its an ticaries effect by in c o rp o ra tio n in to e n a m e l as flu o ra p a tite , thereb y in creasin g th e resistan ce of th e to o th to ac id d isso lu tio n . S in ce th en , how ever, it h as becom e in creasin g ly ev id en t th a t other, p o ssib ly m ore im po rtan t, m e ch an ism s of flu o rid e action are o p era tiv e. E p id e m io lo g ic stu d y failed to d em o n strate co n siste n t corre latio n s b etw een caries p rev alen ce an d th e f lu o r id e c o n t e n t o f th e o u te r e n a m e l la y e r s .16 C o n v e rs e ly , v e ry sm all co n cen tratio n s of flu o rid e, co n tin u a lly p re se n t in th e m o u th , effec tiv ely p rev e n ted caries in rats, a n d th e level of p ro tec tio n w as n o t related to th e am o u n t of flu o rid e acq u ired by th e en am el.17 O th er ex p erim en ts sho w ed th a t lo w c o n c e n tra tio n s of flu o rid e w ere capable of rem in efalizin g in c i p ie n t carious le sio n s18 an d of in terfer in g w ith g ly c o ly tic a c t i v i t y a n d g ro w th of p la q u e b a c te ria .19 T h ese fin d in g s w ere in acco rd w ith rep o rts th a t caries in h u m a n s w as p artially p rev en ted b y freq u en t to p ical expo su re to lo w do ses of flu o rid e, even th o u g h in c re ase d levels of enam el flu orid e co u ld n o t be d etected .20 In th e aggregate, th is research re su lted in a ra th e r d rastic ch an g e in th e m eth o d s of to p ical flu o rid e therapy; rath e r th a n o ccasional ex p o su res of th e te eth to h ig h co n cen tratio n s of flu oride, it ap p e ared preferable to p ro v id e regular, freq u en t ex p o su re to rela tiv ely d ilu te flu o rid e so lu tio n s. T his w as confirm ed in a series of co n tro lled clin ical tria ls.21 C onsequently, th e N ational Caries Program began, in 1974, a series of d em o n stratio n program s n atio n w id e to te st th e feasibility, cost, a n d p u b lic acceptance of w eekly m o u th rin sin g in sc h o o ls w ith a n 0.2% s o lu tio n of so d iu m flu o rid e. T h e re s u lts estab lish ed th a t su c h pro g ram s w ere h ig h ly co st e ffe c tiv e .22 E stim a te s a re th a t
REVIEW
m o re th a n 13 m illio n s c h o o l-a g e d c h ild re n , m o stly in n o n flu o rid a te d a r e a s , a r e c u r r e n t l y e n r o l l e d in school-based flu o rid e rin se program s o r th e an alo g o u s p ro g ram s of d aily flu o rid e tab let ad m in istratio n . T hese ch ild ren can b e expected to average 30% to 40% few er n ew carious lesions at an an n u a l cost of as little as $0.50 per c h ild . R e ce n t re p o rts su g g e st th e se se lf-a p p lied flu o rid e p ro g ra m s m ay p ro v id e a d d e d p ro te c tio n in flu o ri d ated areas as w e ll.23 S h o u ld com m u n itie s c o n tin u e to a d o p t schoolb ased flu o rid e program s at th e p resen t rate, a m ajor im p act on th e incid en ce of c a rie s in c h ild r e n is in e v ita b le w ith in th e n ex t few years. T he d em o n
concern ab o u t th e u se of sealan ts w as d isp e lle d by th e d em o n stratio n th at, w h en sealan t w as p laced over active caries, th e lesio n s d id n o t progress an d te n d ed to becom e ste rile.27 It m u st be co n clu d ed th a t ad h esiv e se a la n ts affo rd a sim p le , safe, a n d h ig h ly effectiv e w ay to p ro te c t th e m o st v u ln e ra b le are as of th e te e th again st caries. W hy, th en , are sealan ts n o t m ore w id ely u se d in p u b lic h ea lth p rev e n tiv e p ro g ra m s? C ertain ly th e answ er involves th e cost of p rovision, as state law s restrict th e use of sealan ts to licensed d en tists or d en tal h ygienists. We h av e c a lc u la te d th a t, in a h y p o th etical p rev en tiv e program for s c h o o l c h i l d r e n , if s e a la n ts w e r e
Sealants are n ot w id ely used in pu blic health program s because o f cost; state la w s restrict the use of sealants to licen sed dentists or dental hygienists.
stratio n th a t fluoride a p p lie d d aily in gels co uld p rev e n t th e prev io u sly in tractable p roblem of extensive caries in p a tie n ts w h o se salivary fu n ctio n w as d estroyed by th e ra p eu tic irra d ia tio n 24 w as an o th er significant re su lt of recen t flu o rid e research. W e know , how ever, th a t flu o rid e is least effective in p rev e n tin g caries on th e o cclu sal surfaces of p o sterio r teeth. W h eth er th e se especially v ulnerable surfaces co u ld be p ro tected by sealing p its an d fissures w ith ad h esiv e p o ly m ers w as th e questio n stu d ied in a large series of clin ical trials th a t began in th e early 1970s. M ost stu d ies in v olved th e u se of an u ltra v io let lig h t p o ly m erized sealan t a p p lie d to enam el th a t h ad been etched w ith d ilu te acid. T he resu lts of som e of th ese stu d ies h a v e b e e n s u m m a r i z e d b y S ilv ersto n e.25 W ith careful atten tio n to th e te ch n iq u es of ap p licatio n , sealants co u ld be reta in ed in m ore th an h a lf th e treated sites for m ore th a n five years, w ith n e a r c o m p le te p r e v e n tio n of caries.26 P rotection of th e etch ed su r face from salivary co n tam in atio n w as fo u n d to be critical to successful se al a n t a p p lic a tio n , as e tc h e d surfaces w ere ra p id ly rem in eralized on contact w ith o ral flu id s. M ore re c e n t tria ls w ith ch em ically p olym erized sealants h av e also been h ig h ly successful in prev en tin g occlu sal caries.26 O ne early
ap p lied once a year to all n o n cario u s occlusal surfaces, th e cost of p rev e n t ing a single cavity co u ld ran g e from $15 to $26, d e p e n d in g on th e in h e re n t caries su sc ep tib ility of th e p o p u la tio n trea ted . It is im p ro b a b le th a t m an y c o m m u n itie s w ill a d o p t su c h p r o gram s. U n til ad h esiv e sealan ts can be legally a p p lie d by less h ig h ly train ed auxiliaries, th e ir fu ll effectiveness in ca ries p re v e n tio n is u n lik e ly to be realized. N evertheless, th e u se of seal ants is n o w reco m m en d ed in d en tal offices a n d c lin ic s, w h e re re q u ire d p erso n n e l are alread y in place. T opical flu o rid es an d sealan ts are ex te rn a lly a p p lie d p re v e n tiv e te c h n iq u es in te n d e d to in crease th e resist ance of te eth to caries. N atural host defense m ech an ism s m ay also b e o p erative in th e m o u th , a p o ssib ility th at h as receiv ed in creased atte n tio n re cen tly w ith p ro m isin g results. Efforts to prev en t caries by stim u la tio n of th e im m u n e sy ste m h av e a lre a d y b een m entioned. A lso of p o ten tial sig n ifi ca n ce are th e n o n im m u n o lo g ic a n tib acterial co m p o n en ts of saliv a in c lu d in g ly so z y m e , la c to fe rrin , lactoperoxidase, an d other salivary p ro te in s th a t m ay be b acteriacid al o r m ay regulate th e ecology of p laq u e an d the clearance of bacteria from th e m o u th .28 T his is a relativ ely n ew area of in te n sive research. W h eth er th ese factors
ARTICLE
have a key ro le in caries p rev en tio n an d , if so, w h eth e r it is p o ssib le to m a n ip u la te th e ir co n cen tratio n a n d activ ity in saliva are q u estio n s being in v es tigated.
Modifying the diet O f th e research efforts to effectively in terv en e in th e etiologic triad of d e n tal caries, th o se d irected at alterin g d ietary factors have so far m et w ith th e least success. G iven th e p ro cliv ity of a large seg m en t of th e p o p u la tio n , a n d especially of ch ild ren , for sw eet foods, it seem s fu tile to striv e for m ajor changes in d ietary habits, even th o u g h there is co m p ellin g ev id en ce th a t a sharp re d u ctio n in th e a m o u n t,29 or even in th e fre q u e n c y ,30 of su g a rs ea te n w o u ld have a salu tary im p act on caries prev a le n ce . In ste a d , re c e n t re se a rc h h as been d irec ted to id en tify in g an d d e v e lo p in g s u b s ta n c e s th a t m ig h t be a d d e d to s u g a rs to d e c re a s e th e ir cariogenicity, or th a t co u ld serve as ta s te - c o m p e t itiv e , n o n c a r io g e n ic sugar substitutes. In 1971, v a rio u s p h o s p h a te co m p o u n d s ap p eared esp ecially p ro m is ing. In m ore th a n 100 ex p erim en ts on an im als, p h o sp h a te s ad d e d to food a n d d rin k in g w ate r h a d effectiv ely p r e v e n te d m o s t c a r ie s .1 H o w ev er, m ost su b seq u en t trials in h u m an s in w h ich d ic alc iu m or d ih y d ro g en p h o s p h a te s w ere a d d e d to flo u r, b read , su g ar, ch e w in g g u m , an d breakfast cereals en d e d w ith eq uivocal results, alth o u g h th e p h o sp h a te ad d itiv e a p p eared to red u c e th e cario g en ic p o te n tia l o f c h e w in g g u m .31 S im ila rly , so d iu m trim e tap h o sp h ate , w h ich h ad been th e m ost effective co m p o u n d of those stu d ied in anim als, failed to p re v en t caries to an y sig n ifican t degree w h en given in ch ew in g gum to c h il d re n .32 It is likely th ese d isa p p o in tin g resu lts can be ex p lain ed by the fact that, in ex p erim en ts w ith anim als, th e p h o sp h a te co m p o u n d s w ere p resen t in all food a n d w ater c o n s u m e d , w h erea s, in ex p erim en ts w ith h u m an s, only in term itten t, an d p robably inad eq u ate, ex p o su re to th e co m p o u n d s w as ac c o m p lish e d . E ven so, th e id e a of a sugar ad d itiv e th a t w o u ld prev en t or atten u a te th e effect of acid p ro d u ctio n in p laq u e rem ain s an attractiv e one; p re su m a b ly th e u se of su c h a su b s ta n c e w o u ld r e q u ir e lit t l e o r n o ch an g e in food tech n o lo g y or personal Carlos : PREVENTION OF DENTAL CARIES ■ 195
REVIEW
ARTICLE
habits. T h is is an area of investigation th a t d eserv es ren e w e d a tte n tio n by b o th caries researchers and th e food in d u stry. T en years ago, it w as also th o u g h t th a t g lu cose an d fructose m ig h t be less c a rio g e n ic s u b s titu te s fo r su c ro se . T h is w as n o t su b sta n tia te d by su b se q u e n t re se a rc h in a n im a ls ,33 b u t m a n y o th e r p o s s ib ilitie s ex ist. F or exam ple, w h en young a d u lts ate diets in w h ic h all ad d ed sugars h ad been su b stitu te d by th e polyol xylitol, v ir tu a lly no caries occurred d u rin g th e 25-m onth study, in contrast to su b s ta n tia l le v e ls of c a rie s in c id e n c e am ong g roups eating diets sw eetened w ith su c ro se or g lu c o se .29 B ecause som e q u estio n s have been raise d co n cern in g its safety, xylitol is n o t yet available in th e U nited States, b u t it is w id ely u se d in confections in som e E u ro p ean countries. Of th e m any sy n th etic sw eeteners th a t h ave been identified, th e d ip e p tid e asp artam e cu rren tly appears m ost p ro m isin g as a n oncariogenic sugar su b stitu te, especially in dry foods.34 T h is c o m p o u n d is u n d e r review by th e F ood a n d D rug A d m inistration. O ther p o te n tia l ca n d id a tes of natu ral origin in c lu d e T h au m atin , a sw eet protein, a n d g ly cy rrh izin , a salt of an acid from lico rice root. Each of th e sugar su b sti tu te s c u rren tly u n d e r stu d y has one or m o re shortcom ings, such as h ig h cost or p o o r so lu b ility or therm olability, th a t w o u ld lim it its u se to certain types o f sn ack foods. T herefore, w e m ay ex p e c t a v ariety of n ew sw eeteners to ev e n tu a lly be m arketed. E ven w h e n su ita b le su g ar su b sti tu te s becom e available, it w ill n o t be feasible or d esirable to su b stitu te th em for all ad d e d sugars. Rather, it w ill be n ecessary to id en tify th o se foods that c o n t r i b u t e m o s t h e a v i l y to t h e cario g enic p o te n tia l of th e A m erican d ie t an d th a t sh o u ld therefore be given p rio rity for reform ulation. U n til re cen tly , little research data existed on th e c a rio g e n ic p o te n tia l of sp e cific com m on food item s. B ecause ethical co n sid eratio n s p rec lu d e th e ev a lu a tio n of th e cariogenicity of foods by c o n v en tio n al clin ical trials, several a t te m p ts h a v e b e e n m a d e to d e v is e screen ing system s based on in vitro, an im al, or short-term h u m a n ex p e ri m ents. T he m ost prom isin g system s rep o rted so far involve the m easu re m e n t of acid p ro d u ctio n in plaq u e in situ w h ile h u m a n volu n teers eat the 196 ■ JADA, Vol. 104, February 1982
te st foods,35 an d a h ig h ly co n tro lled a n d re p ro d u cib le rat-feeding system dev elo p ed in th e N ational Caries P ro gram laborato ries.36 T he latter te c h n iq u e p ro d u ce d data th a t can be u se d to a s s i g n to e a c h f o o d t e s t e d a “ cariogenic p o te n tia l in d e x ,” relativ e to th a t of p u re sucrose. A co m b in atio n o f th e se m e th o d s co u ld be u s e d to b e g in to d e v e lo p d a ta to id e n tif y d ietary co n stitu e n ts of greatest in te rest for caries p rev en tio n .
Improving delivery and acceptance of cariespreventive methods P rogram s to p rev e n t d e n ta l caries m u st co m p ete for in c re asin g ly scarce r e sources w ith other h ealth , p erso n al, a n d s o c ie ta l n e e d s. U n fo rtu n a te ly , d e n ta l h e a lth is ra re ly g iv e n h ig h p rio rity in su c h situ atio n s. T herefore, it is n o longer sufficient to search for caries-preventiv e m eth o d s th a t h av e a h ig h deg ree of b io lo g ic efficacy; to have any substan tial im p act on caries prevalence, p rev en tiv e m e th o d s m u st
d en tly su ch program s are rea d ily ac cep ted in b oth u rb an an d ru ral set tings. (A cceptance h as been su b stan tia lly lo w e r am o n g o ld e r c h ild re n . H ow th is gro u p can be m ore su ccess fu lly m o tiv ated is a research q u estio n th a t needs an early solution.) T h e low co st of self-ap p lied flu o rid e pro g ram s a ris e s fro m th e fac t th a t a d e q u a te su p e rv isio n can be p ro v id ed by class room teach ers or ad u lt v o lu n teers after very brief train in g . In d ee d , im p ro v in g th e cost-effectiv e n e s s o f te c h n iq u e s to p r e v e n t caries alm o st alw ays involves fin d in g w ays to red u c e th e cost of p rovision; few p rev e n tiv e m ethods, eith er av a il able or an ticip ate d , are in h e re n tly ex pen siv e. In general, m eth o d s th a t re q u ire freq u en t, one-on-one co n tact b e tw e e n th e r e c ip ie n t a n d a h ig h ly train ed p ro v id er w ill te n d to h av e poor cost-effective characteristics, as is cu r re n tly th e case w ith adh esiv e sealants. In th is reg ard , recen t research on th e ad a p ta tio n of co ntrolled, slow -release d eliv ery tech n o lo g y for in trao ral u se h as p ro d u c e d som e en co u rag in g re sults. T h e ratio n ale for slow -release
Each o f the sugar substitutes n ow under study has one or m ore shortcomings, such as high cost or poor solubility, that w ou ld lim it its use to certain types o f snack foods.
also be deliverab le to large segm ents of th e p o p u la tio n , at low cost and, p ro b a bly, w ith m in im al req u irem en ts for p o sitiv e actio n o n th e p a rt of th e in te n d e d recip ien ts. C om m unity w ater flu o rid atio n rem ain s th e arch ety p ical exam ple of a p rev en tiv e p ro g ram th a t satisfies th e se criteria, b u t other a ttra c tiv e p o ssib ilities for im proved d eliv ery system s h av e em erged d u rin g th e p ast several years. School-based, self-applied flu o rid e program s offer an in ex p en siv e w ay to pro v id e p artial p rev en tio n of caries to large n u m b ers of ch ild ren , in te rfe r in g only m in im ally w ith n o rm al ac tivities. In a series of co m m u n ity d em o n s tr a tio n s of th is te c h n iq u e c o n d u c te d b y th e N atio n al C aries P ro g ra m , m o re th a n 80% of e l ig ib le elem e n ta ry sch o o l c h ild re n p a rtic i p a te d , w ith p a re n ta l c o n s e n t; e v i
system s rests on th e assu m p tio n th a t sm all co n cen tratio n s of an active ag en t ca n p ro d u ce a th e ra p eu tic resu lt, if th e ag en t is co n stan tly p resen t at th e ta rg et site. O f equal im p o rtan ce, slow -release c h e m o th e ra p y re q u ire s o n ly o c c a sio n al co n tact w ith th e p atien t, th u s red u c in g p ro v isio n costs. A t p r e s e n t, th e m o st d e v e lo p e d slow -release system for caries p rev e n tio n is a flu o rid e -c o n ta in in g , in e rt p o ly m er d ev ice th a t can be te m p o rar ily attac h ed to p artial d en tu re s, or th o d o n tic ap p lian ces, or d irectly to a tooth. In tests w ith h u m a n volu n teers, th ese dev ices w ere w ell to lerated an d fu n ctio n ed w ith satisfactory precisio n . T h ey h av e been fabricated to release co n stan t, p red e term in e d rates of flu o rid e for u p to six m onths, an d sh o u ld be su itab le for th e d elivery of o th er an ticaries ag en ts as w ell.37
REVIEW
E v en th e m o st c o s t-e ffe c tiv e m e th o d s to p rev e n t caries w ill n o t be u se d u n le ss th e in te n d e d rec ip ien ts are aw are of th e po ten tial benefits an d seek o r ac ce p t th e req u ired regim en. Efforts to im prove th e p u b lic ’s u n d e r sta n d in g of th e causes a n d p rev en tio n of caries h ave certainly increased d u r ing rec en t years, b u t m u c h rem ains to be done. F or exam ple, there is no ap p a re n t reason except lack of k n o w l ed g e w h y all scho o lch ild ren , or at least th o se in n o n flu o rid ate d com m unities, s h o u ld n o t be p a rticip a tin g in self a p p lie d program s. T his is a short-term goal th a t is w o rth a concentrated e d u catio n al effort by th e en tire d ental p ro fession.
Conclusions By an y s ta n d a rd s, p ro g re ss to w a rd caries p rev e n tio n has been im pressive d u rin g th e p ast decade. It is arguable th a t m ore inform ation on th e precise etiology of caries an d on p o ten tial n ew p rev en tiv e m eth o d s has been acquired d u rin g th e 1970s th a n in an y com para b le p erio d previously. S u bstantial ad v an ces h ave b een m ad e to w ard th e u n d e rsta n d in g of th e com plex in te rac tio n am ong oral m icroorganism s, h o st resistan ce, an d dietary substrate in th e in itiatio n a n d progression of a caries lesion. T he various m echanism s of ac tio n of th e flu o rid e io n h av e b e e n fu rth e r elu cid ated ; vaccin atio n again st c a r ie s a n d a r e d u c tio n in th e ca rio g en ic p o te n tia l of sw ee t foods h a v e b o th b e c o m e r e a l i s t i c p o s sibilities. C o n s p ic u o u s su c ce sses h av e also b een ach iev ed in th e ap p lica tio n of ex istin g k now ledge. A t least 12 m il lio n m ore ch ild re n th an in 1971 are re c e iv in g p a rtia l p ro te c tio n a g a in st caries th ro u g h se lf-a p p lied flu o rid e program s. O ther effective p reventive m eth o d s, in c lu d in g adhesive sealants an d , p o ssibly, an tim icro b ial agents, co u ld be w id ely an d advantageously u tiliz e d if m an p o w er an d reg ulatory co n stra in ts w ere overcom e, as th e ir scien tific feasibility has, for th e m ost part, alre ad y been dem onstrated. Of course, it w o u ld be naive to p re d ic t th e early d isap p earan ce of dental caries as a m ajor h ealth problem . T h is w ill o ccur on ly gradually, an d w ill re
q u ire a m u c h m ore ex ten siv e u se of p re v e n tiv e m e th o d s— th o se a lre a d y available as w ell as th o se still b eing d eveloped by research. N evertheless, a m ajor step tow ard th e goal of caries p re v e n tio n h as a lre ad y b een tak en , an d th ere is good reaso n to expect even m ore rap id progress d u rin g th e 1980s.
Dr. Carlos is director, National Caries Program, National Institute of Dental Research, National Institutes of Health, Bethesda, Md 20205. Re quests for reprints should be sent to the author. 1. Scherp, H.W. Dental caries: prospects for prevention. Science 173:1199-1205, 1971. 2. Fitzgerald, R.J., and others. The effects of a dextranase preparation on plaque and caries in hamsters, a preliminary report. JADA 76:301-304, 1968. 3. Duany, L.F., and others. Effect of dextranase on oral health in children. J Prev Dent 2(2):23-27, 1975. 4. Gibbons, R.J., and Van Houte, J. Bacterial adherence in oral microbial ecology. Ann Rev Microbiol 29:19-44, 1975. 5. Van Houte, J. Oral bacterial colonization: mechanisms and implications. Microbial Abstr (suppl vol IJ:3-32, 1976. 6. Rolla, G,; Bonesvoll, P.; and Opermann, R. Interactions between oral streptococci and sali vary proteins. Microbiol Abstr (supp vol II):227241, 1979. 7. Gibbons, R.J. On the mechanism of bacterial attachment to teeth. Microbiol Abstr (suppl vol I):267-273, 1979. 8. Bratthall, D., and Kohler, B. Streptococcus mutans serotypes: some aspects of their identifi cation, distribution, antigenic shifts and relation ship to caries. J Dent Res 55 (special issue C):C15-21, 1976. 9. Hardie, J.M., and Bowden, G.H. The micro bial flora of dental plaque: bacterial succession and isolation considerations. Microbiol Abstr (suppl vol I):63-87, 1976. 10. Mikx, F., and others. Effect of Actinomyces viscosus on the establishment and symbiosis of Streptococcus mutans and Streptococcus sanguis in SPF rats on different sucrose diets. Caries Res 9:1-20, 1975. 11. Tanzer, J.M., and others. Diminished viru lence of glucan-synthesis defective mutants of Streptococcus mutans. Infect Immun 10:197-203, 1974. 12. Bowen, W.H. A vaccine against dental caries: a pilot study in monkeys. Br Dent J 126:159-160, 1969. 13. Bowen, W.H. Relevance of caries vaccine investigations in rodents, primates and humans: critical assessm ent. Im m un Abstr (special suppl):ll-20, 1976. 14. McGhee, J.R.; Mestecky, J.; and Arnold, R.R. Induction of secretory antibodies in humans following ingestion of Streptococcus mutans. Adv Exp Biol 107:177-184, 1978. 15. Loe, H.; von derFehr, F.R.,and Shiott, C.R. Inhibition of experimental caries by plaque pre vention. Scand J Dent Res 80:1-9, 1972.
ARTICLE
16. DePaola, P.F., and others. A pilot study of the relationship between caries experience and surface enamel fluoride in man. Arch Oral Biol 20(12):859-864, 1975. 17. Larson, R.H., and others. Caries inhibition in the rat by water-borne and enamel-borne fluo ride. Caries Res 10:321-331, 1976. 18. S ilv ersto n e , L.M. R em in eralizatio n phenomena. Caries Res 11 (suppl l):59-74,1977. 19. Hamilton, I.R. Effects of fluoride on en zymatic regulation of bacterial carbohydrate metabolism. Caries Res ll(su p p l l):262-278, 1977. 20. Shern, R.; Driscoll, W.; and Korts, D. Enamel biopsy results of children receiving fluo ride tablets. JADA 95:310-315, 1977. 21. Horowitz, H.S. The prevention of dental caries by mouthrinsing with solutions of neutral sodium fluoride. Int Dent J 23:585-590, 1973. 22. Miller, A.J., and Brunelle, J.A. Fluoride rinses. In Stewart, R.D., and others. Pediatric den tistry: scientific foundations and clinical practice. St. Louis, C. V. Mosby Co, 1982. 2 3 ..D risco ll, W .S., and o th ers. C ariespreventive effects of daily and weekly fluoride mouthrinsing in a fluoridated community.J Dent Res 60 (special issue A), abstr no. 647, 1981. 24. Dreizen, S., and others. Prevention of xerostomia-related dental caries in irradiated cancer patients. J Dent Res 56(1):99-104, 1977. 25. Silverstone, L.M. Preventive dentistry. London, Update Books, 1978, p 97. 26. Horowitz, H.S.; Heifetz, S.B.; and Poulsen, S. Retention and effectiveness of a single applica tion of an adhesive sealant in preventing occlusal caries: final report after five years of a study in Kalispell, Montana. JADA 95:1133-1139, 1977. 27. Handelmann, S.L.; Buonocore, M.G.; and Schoute, P.C. Progress report on the effect of a fissure sealant on bacteria in dental caries. JADA 87:1189-1191, 1973. 28. Mandel, I.D. Salivary factors in caries pre diction. Microbiol Abstr (suppl):147-158, 1978. 29. Scheinen, A., and Makinen, K.K. The Turku sugar studies I-XXI. Acta Odontol Scand 32:383-412, 1974. 30. Gustafsson, B.E., and others. The Vipeholm dental caries study. The effect of different levels of carbohydrate intake on caries activity in 436 individuals observed for five years. Acta Odontol Scand 11:232-364, 1954. 31. Mandel, I.D. Effect of dietary modifications on caries in humans. J Dent Res 49(suppl):12011211,1970. 32. Finn, S.B., and others. The effect of sodium trimetaphosphate (TMP) as a chewing gum addi tive on caries increments in children. JADA 96:651-655, 1978. 33. Bowen, W.H. Role of carbohydrates in den tal caries. Feeding, weight and obesity abstr (spe cial suppl):147-152, 1978. 34. Bost, R.G., and Ripper, A. Aspartame: a com m ercially feasible aspartic acid based sweetener. Feeding, weight and obesity abstr (special suppl}:269-281, 1978. 35. Muhlemann, H.R. Intra-oral radio tele metry. Int Dent J 21:456-461, 1971. 36. Bowen, W.H., and others. A method to as sess cariogenic potential of foodstuffs. JADA 100:677-681, 1980. 3 7 . M ir th , D .B ., a n d B o w e n , W .H . Chemotherapy: antimicrobials and methods of delivery. Microbial Abstr (suppl vol I):249-262, 1976.
Carlos : PREVENTION OF DENTAL CARIES « 1 9 7