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Infiltrating/Sealing Proximal Caries Lesions : A 3-year Randomized Clinical Trial


S. Martignon, K.R. Ekstrand, J. Gomez, J.S. Lara and A. Cortes
J DENT RES 2012 91: 288 originally published online 17 January 2012
DOI: 10.1177/0022034511435328

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RESEARCH REPORTS
Clinical

S. Martignon1*, K.R. Ekstrand2,


J. Gomez1, J.S. Lara1,
Infiltrating/Sealing Proximal
and A. Cortes1 Caries Lesions: A 3-year
1
Caries Research Unit UNICA, Dental Faculty, Universidad El
Bosque, Cra. 7B Bis No. 132-11, Bogotá, Colombia; and
Randomized Clinical Trial
2
Section of Cariology, Endodontics, Paediatric Dentistry and
Clinical Genetic, School of Dentistry, Faculty of Health
Sciences, University of Copenhagen, Copenhagen, Denmark;
*corresponding author, martignonstefania@unbosque.edu.co

J Dent Res 91(3):288-292, 2012

Abstract Introduction
This randomized split-mouth controlled clinical
trial aimed at assessing the therapeutic effects of
infiltration vs. sealing for controlling caries pro-
gression on proximal surfaces. Out of 90 adult
W ith modern dentistry, preservation of the dental structure and avoidance
of surgical treatment have become treatment goals (Ekstrand et al.,
2001, 2009; Kielbassa et al., 2009; Splieth et al., 2009). Consequently, suc-
students/patients assessed at university clinics and cessful non-operative treatment initiatives have been developed, such as seal-
agreeing to participate, 39, each with 3 proximal ing of proximal early lesions (Martignon et al., 2006, 2010a) and infiltration
lesions identified radiographically around the with a resin capable of effectively penetrating the lesion pores (Paris et al.,
enamel-dentin junction to the outer third of the 2007; Meyer-Lueckel and Paris, 2008). Studies in young adults (Paris et al.,
dentin, were included. Lesions were randomly 2010) and children (Ekstrand et al., 2010) have shown a significantly higher
allocated for treatment to test-A (Infiltration:
efficacy of resin infiltration on early proximal lesions after a short period of
ICON-pre-product; DMG), test-B (Sealing: Prime-
Bond-NT; Dentsply), or control-C (Placebo). time in comparison with placebo or conventional non-operative measures.
Primary outcome after 1, 2, and 3 yrs of radio- This study was conducted on young adults with the aim of comparing the
graphically observed lesion progression was therapeutic effects of infiltrating vs. sealing proximal caries lesions and pla-
assessed by an independent examiner blinded to cebo treatment after 1, 2, and 3 yrs. The outcome (lesion progression) was
groups, using pair-wise and digital-subtraction evaluated by radiographic techniques.
readings. No adverse events occurred. In 37 par-
ticipants assessed after 3 yrs, 10 lesions (A-4; B-2;
C-4) progressed deep into dentin and needed oper- Materials & Methods
ative treatment. The 3-year therapeutic effect, This split-mouth placebo-controlled randomized clinical trial was conducted
based on pair-wise radiographic readings between
on 16- to 35-year-old individuals in Bogotá, Colombia. Sample size calcula-
infiltration and placebo, was 37.8% (95%CI: 20.5-
55.2%) and that between sealing and placebo was tion was based on parameters from a previous proximal sealing study
29.7% (95%CI: 20.2-35.0%). One-year follow-up (Martignon et al., 2006): difference of control (84%) vs. test (43%) progres-
digital-subtraction readings showed significant sion percentages (41%); and proportion of discordant pairs (56%), α = 0.05,
differences in lesion progression between infiltra- 1–β = 0.8. The calculated sample size was 22 persons. With an expected 30%
tion and placebo (P = 0.0012) and between sealing drop-out after 3 yrs, at least 29 participants were to be included.
and placebo (P = 0.0269). The study showed that Ethical approval was obtained from the Ethical Board at the Universidad
infiltration and sealing are significantly better than El Bosque (IRB-089, 2008) (protocol available).
placebo treatment for controlling caries progres- The study population was comprised of students/patients from Universidad
sion on proximal lesions. No significant difference El Bosque who were approached in 2008 for participation in the 3-year study.
was seen between infiltration and sealing Exclusion criteria and study flow are outlined in Fig. 1. The study was
(ClinicalTrials.gov number CT01417832).
explained to potential participants by two of the authors (JSL, AC), who
informed them that infiltration and sealing are alternative preventive treat-
KEY WORDS: caries treatment, clinical studies/ ments for early proximal lesions, and that 2 initial bitewing radiographs
trials, radiography, resin(s), caries detection/diag- would be made to search for 3 of these lesions. Of the 680 people approached,
nosis/prevention, preventive dentistry. 90 agreed to participate (providing written informed consent) in the study and
had the first set of radiographs made.
DOI: 10.1177/0022034511435328
In all cases, participants were referred for operative treatment if needed.
Received September 28, 2011; Last revision December 06,
To be included in the study, participants were required to have at least 3 radio-
2011; Accepted December 12, 2011 graphically observed caries proximal lesions in the posterior teeth, with a
score of 3 or 4 (SM) in the following modified radiographic scoring system
© International & American Associations for Dental Research (Martignon et al., 2006): 0, no radiolucency; 1, outer half of enamel; 2, inner

288
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J Dent Res 91(3) 2012 Infiltrating vs. Sealing Proximal Caries   289

half of enamel; 3, around the enamel-


dentin junction (EDJ); 4, outer third of
dentin; 5, middle third of dentin; 6, inner
third of dentin; and 7, not assessable.
The final population was comprised of
39 individuals (117 lesions) who signed
the consent form. For these participants,
two appointments were planned.
At the first visit, standardized geo-
metrically aligned bitewing radiographs
were obtained, with individual biting
registers made with silicone impression
material. Proximal surfaces of posterior
teeth were radiographically classified by
one trained examiner (SM). If a partici-
pant had more than 3 eligible lesions, 3
were randomly selected (AC). Then, a
clinical examination was conducted to
assess DMF-T/S (D, diagnostic thresh-
old: cavitated level), and individual car-
ies risk assessment was completed with
the Cariogram program 3.0 (Bratthall et
al., 2008), including assessment of all 9
factors with the aid of a salivary test kit
(CRT®, Vivadent, Schaan, Liechtenstein).
Furthermore, the gingival ‘not-bleeding/
bleeding’ status of the papillae relative to
the selected lesions was assessed after
gentle air-probing (Ekstrand et al.,
1998). At that point, orthodontic elastic
bands were placed next to the selected
lesions.
The second appointment was two
days later. Using the ICDAS criteria
(Ismail et al., 2007), the previous exam-
iner conducted a visual-severity scoring
of the selected cleaned proximal-surface
lesions. The lesions’ activity status was Figure 1.  Study flow diagram.
assessed according to the combination of
4 indicators following a modified points system (Ekstrand et al., (Prime Bond NT®; Dentsply, York, PA, USA) (Martignon et al.,
2007): plaque-stagnation area (1-no; 2-yes); visual appearance 2006). The placebo treatment (C) consisted of a micro-brush
(1-brown-spot lesion; 3-white-spot lesion; 4-surface break- passed through the spaces between teeth for 30 sec, with the
down); tactile feeling (2-smooth; 4-rough); and papilla bleeding procedure repeated after 2 min. All individuals received routine
(0-no; 1-yes). The lesion was considered as active if the sum of instructions on flossing.
points was ≥ 8. Participants were clinically examined after 1, 2, and 3 yrs by
The 3 lesions were randomly allocated (in randomly per- one examiner (JSL) blinded to the selected treatment groups. In
muted blocks generated by SPSS) to 1 of 3 groups undisclosed cases of general presence of obvious cavitated lesions, the par-
to the participants (AC): A, Infiltration; B, Sealing; C, Placebo. ticipant was referred for operative treatment. Standardized bite-
Treatments were conducted (by SM, blinded to lesions’ scores), wing radiographs were made annually.
with rubber-dam isolation and plastic wedges. Infiltration (pro-
cedure A) was conducted with the ICON® pre-product (DMG, Radiographic Assessment
Hamburg, Germany), which, instead of the market-available
application kit, came with individual vials and a plastic-strip An independent examiner (JG) assessed the radiographs by reading
teeth separator. The procedure included: plastic-strip isolation of lesions A, B, and C in a randomized order, regardless of the par-
adjacent teeth; selected-surface etching with 15% hydrochloric ticipant number and group. Reading of images was conducted after
acid (120 sec); rinsing and drying; 95% ethanol- and air-drying; 1 yr by digital-subtraction radiography of scanned images (Image
resin infiltration with a syringe (120 sec); polymerization, and Tool®, UTHSCSA, San Antonio, TX, USA) and in terms of pair-
infiltrant re-application (30 sec) plus polymerization. The seal- wise reading of conventional radiographs with the aid of a Mattson’s
ing of the selected lesions (B) was performed with an adhesive magnifying glass (Dental X-ray, Copenhagen, Denmark). After 2

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290  Martignon et al. J Dent Res 91(3) 2012

Table.  Distribution of the Randomly Selected Lesions (A, B, C) According to Tooth Surface and Radiographic Score

Tooth 14/24 15/25 16/26 17/27 34/44 35/45 36/46 37/47 Total

Surface M D M D M D M D M D M D M D M D  

Infiltration (A)
Score 3 1 1 2 1 1 0 0 0 0 1 1 6 1 1 0 0 16
Score 4 0 1 3 6 4 1 0 0 0 0 1 3 3 1 0 0 23
Sealing (B)
Score 3 0 3 0 0 2 0 0 0 0 0 1 5 2 1 0 0 14
Score 4 0 8 5 3 2 0 0 0 0 0 1 3 1 1 1 0 25
Placebo (C)
Score 3 0 2 2 2 0 2 1 0 0 1 3 2 0 0 0 0 15
Score 4 0 2 4 5 1 2 1 0 0 1 1 4 1 2 0 0 24
Total 1 17 16 17 10 5 2 0 0 3 8 23 8 6 1 0 117

therapeutic effect (difference in the proportions of lesion progres-


sion between test and control groups) and the 95% confidence
intervals (Siegel and Castellan, 2002). In all tests, p-values less than
0.05 were considered significant.

Results
Baseline
The sample included 28 women and 11 men, with a mean age of
21 yrs (range, 16-31 yrs). The mean DF-T of the sample was 4.9
± 3.4, and the DF-S corresponded to 7.0 ± 5.9 (D-S, 0.6 ± 1.0;
F-S, 6.4 ± 6.0). No teeth were extracted due to caries (M). More
than half of the participants were classified as ‘moderate-very
high’ caries risk (moderate, 28%; high, 21%; very high, 5%),
and the rest (46%) as low caries risk.
The Table demonstrates that most of the selected lesions
Figure 2.  Radiographic pair-wise reading progression of proximal (61.5%) were radiographically classified as score 4; the majority
lesions after 1, 2, and 3 yrs.
were located in the upper teeth (58.1%), and, with respect to tooth
type, more than half were in the second premolars (54.7%).
and 3 yrs, only pair-wise radiograph readings were conducted. For The visual assessment revealed that the majority (88%) of
all readings, the examiner was blinded to whether the lesion was an the selected proximal lesions had an ICDAS score of 2 (A, 90%;
A, B, or C (placebo) lesion. For the pair-wise readings, the most B, 87%; C, 87%), followed by a score of 3 (5%). In 4 cases
recent film was coded and then read against baseline. For reproduc- (3%), the lesion could not be visually assessed. Activity was
ibility assessment, the examiner repeated 20% of radiograph read- assessed in 80/117 lesions (68.4%); in 37 cases, visual and/or
ings by both methods 1 wk after the first reading. tactile access of lesions was not possible. Of these, 64.9% were
premolar teeth. Of the 80 lesions, 26/27 in group A, 26/27 in
Statistical Analysis group B, and 24/26 in group C were assessed as active.
The intra-examiner reliability for the pair-wise and the digital-
subtraction radiographic readings was assessed by unweighted Follow-up
kappa scores (Landis and Koch, 1977). Caries experience (DMF- Only two participants (5%), one during the first and one during
T/S), individual caries risk levels, ICDAS criteria, radiographic the second year, dropped out of the study. No unwanted side-
scores, and progression status of selected lesions were reported effects (pain, vitality loss, staining) were observed. During the
descriptively. The outcome variable of lesion progression during study period, 10 cases (A-4; B-2; C-4) showed radiographic
the 1-, 2-, and 3-year study period was assessed by pair-wise radio- lesion progression reaching the middle third of dentin and were
graphic reading. Results of the digital-subtraction radiography were referred for operative treatment.
reported after 1 yr only. The placement of a restoration during the
study period was considered as lesion progression. Differences in
Pair-wise Reading of Radiographs
lesion progression between treatments at each follow-up were ini-
tially tested by the Cochran Q test (Siegel and Castellan, 2002). In Fig. 2 demonstrates the 1- (n = 38), 2- (n = 37), and 3-year pro-
case of significant difference between groups, the McNemar gression results (n = 37) of the pair-wise readings. Three-year
Change test for related groups was conducted, including the percentages were: 32% infiltrated, 41% sealed, and 70% placebo
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J Dent Res 91(3) 2012 Infiltrating vs. Sealing Proximal Caries   291

cases, with significant progression rate


differences between treatments at the 3
follow-ups (Cochrane Q test p-values <
0.01). Significant differences (McNemar
test) were observed between infiltration
and placebo after 1 (χ2= 8.643; P =
0.0033), 2 (χ2= 10.563; P = 0.0012), and
3 yrs (χ2= 10.563; P = 0.0012), and
between sealing and placebo after 3 yrs
(χ2= 4.762; P = 0.0291).
The therapeutic effects between infil-
tration and placebo were 31.6% (95%CI:
15.1-48.1%) after 1 yr, 37.8% (95%CI:
20.5-55.2%) after 2 yrs, and 37.8%
(95%CI: 20.5-55.2%) after 3 yrs.
Between sealing and placebo, the thera-
peutic effect after 3 yrs was 29.7%
(95%CI: 20.2- 35.0%).
Figure 3.  3-year radiographic behavior of test A, test B, and C (placebo) lesions.
Digital-subtraction Radiography
The 1-year follow-up digital-subtraction readings showed pro- Since only two participants left during the study, leaving 37
gression in 10 (A), 16 (B), and 24 (C) cases (Cochrane Q test; p participants, no drop-out analysis was conducted.
< 0.001), with significant differences in lesion progression The participants represented a higher socio-economic status
between infiltration and placebo (χ2= 10.563; P = 0.0012) and and a lower caries experience than a population from the same
between sealing and placebo (χ2= 4.900; P = 0.0269). age group in Bogotá (Ministerio de Salud – República de
Colombia, 1999). With the split-mouth design, individual par-
Behavior of Lesions ticipant variables (observer and information bias) were
accounted for, eliminating the concern that there would be dif-
Fig. 3 shows the pair-wise radiographic-reading behavior of the
ferences in lesion progression between the lesions selected for
lesions after 3 yrs for each group according to their baseline code
the different treatment modalities.
and their progression status. Overall, the highest lesion progres-
The caries progression protective effect of the infiltration for
sion was observed in group C, with highest progression for base-
proximal lesions is in accordance with recent studies conducted
line lesions into dentin (code 4: 74%) vs. those around the EDJ
in young adults (Paris et al., 2010) and children (Ekstrand et al.,
(code 3: 64%). Fewer lesions with a radiographic code 3 pro-
2010). The higher infiltration efficacy with digital-subtraction
gressed in group A (7%) in comparison with group B (38%),
radiography reported after 18 mos (93%) (Paris et al., 2010), in
while the trend was opposite for code 4 lesions (50% and 46%,
comparison with that of the current study (74%), might be
respectively).
related to the fact that the previous study included several
lesions located in enamel, while this study mostly included den-
Intra-reliability Radiograph Readings tin lesions (scores 3-38% and 4-62%), and it is well-known that
dentin lesions tend to progress faster than enamel lesions
The intra-reliability for the pair-wise and the subtraction radio-
(Mejàre et al., 1999; Martignon et al., 2010b).
graphic methods (kappa values) was 0.74 and 0.78, respectively.
As for the sealing, a 57% efficacy, shown in a previous
18-month study in young adults with the paired-radiograph
Discussion method (Martignon et al., 2006), is similar to that of this study
after 2 (60%) and 3 yrs (60%). Still, in this study, significant
The results of the present study strongly indicate that caries differences were observed with the pair-wise radiograph read-
infiltration is significantly more efficacious, in terms of the ings when compared with the placebo only after 3 yrs, even
capacity for beneficial change or therapeutic effect of a given though, after 1 and 2 yrs, there was a consistently lower caries
intervention, than placebo treatment for controlling the progres- progression of sealing cases in comparison with placebo cases.
sion of proximal caries lesions after 1, 2, and 3 yrs. Caries seal- In this study, all selected surfaces received a 2-day temporary
ing appeared to be significantly more efficacious than placebo separation for diagnosis purposes and to allow for creating a
after 3 yrs. Analysis of the data also showed no significant dif- working space to place either dental material on the lesion sur-
ference in efficacy between infiltration and sealing during the 3 face. These two appointments to conduct the procedure are no
yrs, even though the infiltration showed a consistently higher longer needed for the infiltrant as with the current isolation
therapeutic effect than the sealing. This statement is based on the applicator it can be done in one session.
pair-wise radiographic readings, but the same trend was seen The fact that more infiltrated than sealed lesions of score 4 pro-
from the subtraction evaluation method after 1 yr. gressed could be related to etching and/or insufficient infiltration. A

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292  Martignon et al. J Dent Res 91(3) 2012

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research, for travel expenses to discuss and/or present the study,
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