Effects of Risk Factors On Periodontal Disease Defined by Calibrated Community Periodontal Index and Loss of Attachment Scores
Effects of Risk Factors On Periodontal Disease Defined by Calibrated Community Periodontal Index and Loss of Attachment Scores
Effects of Risk Factors On Periodontal Disease Defined by Calibrated Community Periodontal Index and Loss of Attachment Scores
Accepted Article
Article type : Original Manuscript
Chiu-Wen Su1, Amy Ming-Fang Yen2,3, Hongmin Lai4,5 ,Yungling Lee6, Hsiu-Hsi Chen6 ,
2. School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei,
Taiwan
3. Oral Health Care Research Center, College of Oral Medicine, Taipei Medical University,
Taipei, Taiwan
City
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/odi.12678
School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, No.250,
Wuxing St., Taipei 11031, Taiwan. Tel: 02-27361661 ext 5211, Fax: 02-27362295, E-mail:
National Taiwan University, Room 533, No. 17, Hsuchow Road, Taipei, 100, Taiwan., Tel:
Abstract
Objectives: We evaluated whether and how the effects of risk factors on periodontal disease
(PD) were modified by measurement errors using community periodontal index (CPI) and
Methods: A pilot validation study was performed to estimate the rates of false negative and
false positive for both CPI and LA in 31 subjects from different regions using measurements
Taiwanese nationwide survey was conducted by enrolling 3860 participants to estimate the
effect of each risk factor on PD calibrated with both sensitivity and specificity of two indices.
ratio for smoking versus non-smoking was higher than the uncalibrated odds ratio for PD
defined by CPI (2.75(2.01, 3.77) versus 2.02(1.63, 2.52)) and LA (3.85(2.44, 6.13) versus
1.93(1.47, 2.54)) scores. Similar underestimation was noted for other risk factors.
Conclusion: The effects of risk factors on PD measured using CPI and LA in a large
Introduction
presentations varying from mild symptoms and signs (such as gingival bleeding and calculus),
to various degrees of mobility, and finally loss of tooth. To detect PD earlier, the community
periodontal index (CPI) and loss of attachment (LA) are often used to measure dental pocket
depth and destruction of supporting tissue of the teeth and reflect disease severity. More
(Haber et al, 1993; Jan Bergström and Preber, 1994; Kinane and Chestnutt, 2000; Lai et al,
While these epidemiological studies have reported the effect sizes (often reported by
odds ratio or relative risk) of risk factors associated with PD, it is argued that measurement
errors (false negative and false positive) in CPI or LA may affect these estimations. The effect
of measurement errors on the evaluation of risk factors for PD measured by CPI or LA may
not be a serious problem in clinical studies because if PD is severe, its diagnosis is unlikely to
overestimation of the effect sizes for the risk factors of interest in the setting of a community
At this time, few studies have been conducted to address this issue. A previous
and older, used CPI and LA, as measured by a group of trained general dentists, to assess the
render it a candidate study for assessing the impact of measurement errors on effect size. The
aim of this study was to apply a two-stage design: the first stage included a pilot validation
measurement errors to correct the effect sizes of the risk factors associated with PD based on
the calibrated CPI and LA measured by the same examiners in a large-scale community-based
survey to assess whether measurement errors underestimated or overestimated the effect sizes
Study design
In the current study, we used a two-stage study design to estimate sensitivity and
specificity. In the first stage, we conducted a validation study to calibrate the discrepancy in
CPI and LA measurement between the gold standard (a senior periodontist, Lai H) and
dentists after professional training in PD. The estimated sensitivity and specificity from this
pilot study were used to calibrate the association between risk factors and PD obtained from
the main study, a nationwide survey. The periodontal examination was measured by CPI
(WHO, 1997). The examination consisted of CPI scores in the following five categories:
healthy, gingival bleeding, calculus, shallow pockets of 4-5 mm and deep pockets of 6 mm or
deeper (Ainamo et al, 1982). All participants provided informed consent after receiving
sufficient information. This study was approved by the Joint Institutional Review Board of
invited to participate in a validation study comparing their measurements of CPI and LA with
those taken by a senior dentist specializing in periodontology (gold standard). Two trained
dentists selected from each area to participate in the nationwide survey (6 areas: two northern,
one central, two southern, and one eastern area of Taiwan), and one gold standard dentist
examined a total of 31 subjects; these data were included in the analysis of the intra- and
inter-rater reliability of the CPI and LA measurements. We excluded subjects that had
undergone scaling or treatment for periodontitis in two months before calibration. Each
subject was examined by both the trained general and gold standard dentists. All the teeth of
each subject were examined by the different raters at six conventional sites: mesiobuccal,
mid-buccal, disto-buccal, mesiolingual, mid-lingual, and disto-lingual. At each site, CPI and
LA score was measured and recorded. The highest score of all the sites in each sextant was
The main objective of the nationwide survey, commissioned by the Health Promotion
Administration, Ministry of Health and Welfare, Taiwan in 2008, was to explore the
prevalence and severity of periodontal disease and its association with oral hygiene, lifestyle,
one gold standard dentist to measure the sextant-level CPI and LA for 4601 subjects from
different regions. As one dentist did not complete the calibration stage, we excluded data
related to that dentist, leaving twelve dentists and one gold standard dentist and their
measurements on 3860 subjects (17,244 sextants) for inclusion in the current study. These
data were used to calculate the uncalibrated and calibrated ORs for the association between
the risk factors and PD with simultaneous consideration of the correlated properties of
sextant-level data from the same subject or the same region using the following Bayesian
Risk Factors
anthropometric measurements, such as height and weight; lifestyle factors, including cigarette
smoking, alcohol consumption, and betel-quid chewing; and personal diseases, such as type 2
diabetes mellitus. The questionnaire was administered by public health nurses between 2007
differential and non-differential. If the effect size is away from the null hypothesis (no
overestimation of effect size if uncorrected. On the other hand, if the effect size is towards the
underestimation if uncorrected.
Supplementary provides an example demonstrating how the effect size of smoking on the
odds of PD measured by CPI was substantially changed after correcting for the measurement
underestimation of the effect size of smoking, which inflated from 2 to 4.43 for the
uncalibrated and calibrated odds ratios, respectively. This Bayesian hierarchical model may
be further applied to large-scale epidemiological surveys to calibrate the odds ratios of other
risk factors.
Statistical analyses
In order to measure the impact of the risk factors on PD, the attributable proportion
(AR) and population attributable proportion (PAR) were used in the analysis. AR was defined
as the proportion of disease in the exposed group that could be attributed by a given risk
a risk factor were reduced to an alternative exposure scenario. The formula was written as
( %)×( )
Population attributable proportion=( ( %)×( ))
In the calibration study, the estimates of sensitivity and specificity comparing PD status
measured as by participating trained dentists and PD status measured by the gold standard
dentist and their confidence intervals following binomial distribution were reported. For the
level, body mass index (BMI), type 2 diabetes mellitus (DM), and lifestyle factors such as
cigarette smoking and alcohol consumption. To take into account the correlated property of
sextant-level data from the same subject or the same dentist, we applied a Bayesian
hierarchical model with the incorporation of correlated properties (Yen, 2006) and
measurement errors to estimate the calibrated odds ratio between risk factors and PD; we
applied this hierarchical univariate logistic regression model with a random intercept,
accounting for different baselines in the same cluster, to estimate the crude odds ratio (cOR)
for the effect of each risk factor on PD. The random intercept term was assumed to follow a
normal distribution centred at zero with a standard deviation, denoted by σ, which was used
to test whether the random effect is statistically significant. Finally, the hierarchical
also calculated attributable proportion (AR) and population attributable proportion (PAR) for
each risk factor given the estimated adjusted odds ratios before and after calibration. The
estimation of the hierarchical models was accomplished using the Markov chain Monte Carlo
simulation underpinning the developed Bayesian directed acyclic graphic model and
(Spiegelhalter et al, 2004). The 95% confidence interval was extracted from the posterior
distribution of each parameter and reported for the assessment of statistical significance.
Results
The overall sensitivity and specificity of CPI measurement at the sextant level were
0.73 and 0.82. The corresponding figures were 0.67 and 0.73 for LA measurement and 0.78
and 0.69 for CPI and LA. The number of sextants by status of PD with CPI and LA defined
by the gold standard and by participating trained dentists who were involved in the
nationwide survey, and the corresponding estimates of sensitivity and specificity are shown in
Supplementary sTable 1. The results show that measurement errors varied by regions and had
a wide range of positive likelihood ratios (sensitivity/false positive) from 1.12 to 7.71 for CPI
adjusted odds ratios (ORs) with PD defined by CPI ≥3 or LA≥1 as the outcome between the
uncalibrated and the calibrated models. The effect sizes for calibrated cORs for each variable
in the univariate analysis were more considerably further away from the null (cOR=1),
each variable on PD in the absence of calibration. Taking smoking as an example, the cOR
for the odds of PD for smokers vs. non-smokers was two times greater with calibration than
without calibration and increased from 3.42 (2.81, 4.17) to 6.50 (4.65, 9.39). Similar
underestimations of cORs were also noted for other variables with various extents of
non-differential misclassification.
Table 2 also shows that the influence of such non-differential misclassification on the
underestimation of effect sizes was attenuated by adjustment, but the tendency towards
for variables with (multivariate model 2) and without (multivariate model 1) incorporation of
alcohol drinking.
were noted for the association between smoking and PD in the univariate analysis (2.62 (2.19,
3.18) to 4.29 (3.22, 5.84)) and in multivariate analysis 2.02 (1.63, 2.52) to 2.75 (2.01, 3.77).
The calibrated OR was still consistently higher than the uncalibrated OR using different
cut-offs of CPI score (Supplementary sTable 2). These findings suggest such a
note that the alteration of effect size was greater than that observed using CPI alone. However,
such a change was ameliorated when all the variables were considered in the multivariate
analysis.
Table 5 shows the comparison of the proportion of risk for PD attributed to each selected
variable at individual level (AR) and population level (PAR) between the uncalibrated and the
calibrated estimates. For smoking, for example, the estimated AR and PARs increased after
calibration by 14% and 10% for CPI and by 26% and 21% for LA, respectively. The
corresponding figures for other variables were increased by 0~10% of PAR for CPI and by
measurements are subject to a dentist’s subjective judgement and periodontal expertise (such
as probing force and position). Therefore, the potential probability of measurement error for
PD is greater than for other diseases when community-based screening for early detection of
PD is conducted. This may explain why prevalence of PD varied from study to study.
As expected, the periodontal measurement errors in our validation study varied with
region. There were higher sensitivities in the northern and eastern area but more false
negative cases in the central area and two southern areas. For periodontal disease prevalence
surveys, the measurement errors exist across dentists. Therefore, before a nationwide survey,
we had conducted a validation study to assess the measurement errors in the measures for PD
and use them for calibration to improve the accuracy of PD prevalence estimation. Moreover,
the magnitude of the effects of the risk factors on periodontal disease was also affected.
The results of the effect of the calibration of the estimation of effect size for each risk
factor associated with the risk for PD was consistently demonstrated as non-differential
misclassification using either CPI or loss of attachment (LA) score. Specifically, the
calibrated OR was generally higher than the uncalibrated OR, although the underlying effect
to define PD.
The implications of our findings are two-fold for prevention and treatment of PD. First,
calibration, the contribution of this risk factor may be neglected and primary prevention of
PD may not target these risk factors. This can be easily observed from our AR and PAR
results. Second, the biased estimated odds ratio may also affect the risk stratification of PD in
the underlying population and, in turn, may lead to inaccurate individual risk prediction for
PD.
One might be interested to know whether the measurement errors are different by
different sites. Suppose senior periodontist are less likely to include such kind of gingival
recession as the outcome of CPI, the sensitivity of mid-buccal sites is supposed to be lower
than that of other sites in addition to the quality of professional training in the skills of CPI
and LA. It is interesting to assess the impact of measurement errors attributed to this drive
resulting from brushing. Unfortunately, we did not collect data at site-level and only at
sextant level in the main study and we could not re-analyse the data by sensitivity analysis
with and without excluding mid-buccal. However, we can check the influence of this concern
on measurement errors by examining sensitivity and specificity by different sites using data
other sites (47%) for the CPI measurements. The sensitivity of mid-buccal site (56%) was
lower than other sites (67%) for the LA measurements. The impact of lower sensitivity might
underestimate the effect size of the risk factors. However, the analysis of data on the main
study can be only limited to sextant-level due to unavailable information on site level. This is
one of our study limitations. Another limitation is that our periodontal measurements were
sextant-level was determined by index teeth. The highest score of all sites in each sextant was
measurement error at the sextant-level in the validation study can represent measurement
In conclusion, our study shows that the effect of measurement error on PD varied with
dentists and regions. The results of our validation study provide the basis for correcting the
effect size regarding the association between relevant correlates and PD. The estimated odds
ratio for certain risk factor (such as smoking) in association with PD was substantially
underestimated without calibration, which may also undervalue the ability of risk factor
acknowledged the support and participation of the staff of the Keelung, Taipei, Changhua,
Conflict of Interest
Author Contributions
CWS, HHC and SLC conceived the study concept and design. AMY and HL were
responsible for data analysis. AMY, HL, and YLL contributed on interpretation of the results.
CWS wrote the first draft. CWS and AMY contributed on concepts for analysis. HHC and
SLC revised the manuscript. All authors approved the MS before submission.
the World Health Organization (WHO) community periodontal index of treatment needs
Jan Bergström, Hans Preber (1994). Tobacco Use as a Risk Factor. J Periodontol 65:545-550.
Kinane DF, Chestnutt, IG (2000). Smoking and Periodontal Disease. Critical Reviews in Oral
Lai H, Lo MT, Wang PE, Wang TT, Chen TH, Wu GH (2007). A community-based
community-based integrated screening programme (KCIS No. 18). J Clin Periodontol 34:
851-859.
Lai H, Su CW, Yen AM, Chiu SY, Fann JC, Wu WY, Chuang SL, Liu HC, Chen HH, Chen
LS(2015). A prediction model for periodontal disease: modelling and validation from a
Spiegelhalter D, Thomas A, Best N, Lunn D (2004). Win BUGS User Manual Version 2.0.
Petersen PE, Ogawa H (2005). Strengthening the prevention of periodontal disease: theWHO
population-based study on the association between type 2 diabetes and periodontal disease
in 12,123 middle-aged Taiwanese (KCIS No. 21). J Clin Periodontol 36: 372-379.
Yen AM, Liou HH, Lin HL, Chen TH (2006). Bayesian random-effect model for predicting
Univariate Multivariate
Variable Uncalibrated cOR Calibrated cOR Uncalibrated aOR Calibrated aOR
(95% CI) (95% CI) (95% CI) (95% CI)
Gender
1.87 2.64 1.30 1.47
Male/ Female
(1.61, 2.19) (2.08, 3.39) (1.07, 1.57) (1.12, 1.94)
Age
1.06 1.08 1.05 1.07
per year
(1.05, 1.06) (1.07, 1.09) (1.05, 1.06) (1.06, 1.09)
Education
2.75 4.26 1.27 1.44
≤9/ >9 years
(2.33, 3.23) (3.29, 5.65) (1.04, 1.56) (1.10, 1.89)
BMI
1.56 1.99 1.10 1.15
≥25/ <25 kg/m2
(1.32, 1.86) (1.55, 2.58) (0.93, 1.32) (0.90, 1.47)
DM
1.65 2.22 0.99 1.13
pre-DM/ Normal
(1.33, 2.06) (1.62, 3.09) (0.79, 1.25) (0.82, 1.56)
3.28 6.75 1.50 2.26
DM/ Normal
(2.38, 4.56) (4.08, 11.38) (1.07, 2.10) (1.39, 3.71)
Smoking
2.62 4.29 2.02 2.75
Yes/ No
(2.19, 3.18) (3.22, 5.84) (1.63, 2.52) (2.01, 3.77)
Alcohol Drinking
0.85 0.79
Yes/ No -- --
(0.70, 1.03) (0.59, 1.08)
DIC -- -- 15917 16106.8
aOR: Adjusted Odds Ratio
cOR: Crude Odds Ratio
CPI: Community Periodontal Index
DIC: Deviance Information Criterion
Univariate Multivariate
Variable Uncalibrated cOR Calibrated cOR Uncalibrated aOR Calibrated aOR
(95% CI) (95% CI) (95% CI) (95% CI)
Gender
4.01 12.72 2.65 3.88
Male/ Female
(3.30, 4.91) (8.10, 21.50) (2.08, 3.38) (2.58, 6.06)
Age
1.09 1.19 1.07 1.15
per year
(1.08, 1.10) (1.17, 1.22) (1.06, 1.08) (1.13, 1.18)
Education
3.47 22.24 1.29 2.14
≤9/ >9 years
(2.81, 4.28) (13.08, 38.74) (1.00, 1.63) (1.44, 3.21)
BMI
1.82 3.03 0.91 0.86
≥25/ <25 kg/m2
(1.46, 2.28) (1.94, 4.79) (0.72, 1.14) (0.59, 1.23)
DM
2.07 8.35 0.96 1.51
pre-DM/ Normal
(1.56, 2.73) (4.42, 16.73) (0.72, 1.27) (0.93, 2.44)
5.13 48.86 1.49 3.24
DM/ Normal
(3.28, 8.06) (18.77, 148.86) (0.98, 2.25) (1.58, 6.84)
Smoking
4.22 16.28 1.93 3.85
Yes/ No
(3.26, 5.42) (9.23, 30.94) (1.47, 2.54) (2.44, 6.13)
Alcohol Drinking
0.84 0.52
Yes/ No -- --
(0.65, 1.09) (0.26, 0.99)
DIC -- -- 13968.3 14059.6
aOR: Adjusted Odds Ratio
cOR: Crude Odds Ratio
DIC: Deviance Information Criterion
LA: Loss of Attachment
CPI ≥3 or LA ≥1
CPI ≥3
LA ≥1
Education 0.4 1.29 22% 10% 2.14 53% 31%