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Journal of Dental Research
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Clinical

Longitudinal Relationship between Root Caries and Serum Albumin

A. Yoshihara1,*, N. Takano1, T. Hirotomi1, H. Ogawa1, N. Hanada2 and H. Miyazaki1

1 Division of Preventive Dentistry, Department of Oral Health Science, Graduate School of Medical and Dental Sciences, Niigata University, 2-5274 Gakkocho-Dori, Niigata, 951-8514, Japan; and
2 Department of Oral Health, National Institute of Public Health, 2-3-6 Minami, Wako, 351-0197, Japan

Correspondence: * corresponding author, akihiro{at}dent.niigata-u.ac.jp


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Serum albumin levels are a practical marker of general health status in the elderly and have been used to determine the severity of an underlying disease and the risk for death. This longitudinal study evaluated the relationship between serum albumin levels and root caries. A total of 266 persons with at least 1 tooth at baseline underwent a baseline examination and then annual investigations for 6 years. Multiple linear regression analysis was used to assess the relationship between changes in serum albumin levels and the number of root caries lesions over 6 years, after adjustment for confounding factors. Change in the number of root caries lesions was significantly associated with change in serum albumin concentrations. The standardized coefficient was –0.148 (p = 0.024). We can confirm that serum albumin concentration correlates with root caries events. From these data, we conclude that persons with hypoalbuminemia are at high risk for root caries.

Key Words: root caries • geriatric dentistry • serum albumin


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Serum albumin levels are a practical marker of general health status in the elderly and have been used to determine the severity of an underlying disease and the risk for death (Phillips et al., 1989; Shibata et al., 1991). Many conditions, such as inflammatory states, liver diseases, and renal diseases, lead to decreased serum albumin levels (Herrmann et al., 1992; Rigaud et al., 2000; Walrand et al., 2000). Moreover, malnutrition can be monitored by the examination of serum albumin levels (Magagnotti et al., 2000; Giordano et al., 2001; Don and Kaysen, 2004). Recently, studies have shown that serum albumin levels are associated with general health status among the elderly (Corti et al., 1994; Baumgartner et al., 1996). Hypoalbuminemia occurs in a variety of diseases, and is associated with an increased rate of complications during hospitalization. In addition, serum albumin is a possible index of intrinsic aging (Shibata et al., 1991).

In contrast, aging is known to lead to an increase in some oral conditions, such as gingival recession and root caries. Several risk factors for the development of root caries have been identified, including past caries, periodontal status, and salivary levels of cariogenic bacteria (Scheinin et al., 1994; Lawrence et al., 1995; Locker et al., 1996; Powell et al., 1998). Furthermore, some reports indicate a link between general health and dental caries. For example, the composite dental index, which combines caries, periodontitis, and edentulousness, has been linked to ischemic events in persons with coronary heart disease (Mattila et al., 1995). Furthermore, it has been shown that increased dental caries may be associated with an increased immune response (Tenovuo et al., 1990).

Previously, we showed an association between serum albumin levels and root caries in a cross-sectional study of elderly persons (Yoshihara et al., 2003). However, because of the cross-sectional design, we could not confirm a clear relationship between serum albumin concentrations and root caries. This longitudinal study evaluated the relationship between serum albumin concentrations and root caries in elderly persons, after adjustment for confounding factors.


    MATERIALS & METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Participants
A longitudinal study was conducted in older adults residing in Niigata City, Japan. Initially, questionnaires were sent to all 4542 residents aged 70 years (born in 1927). Of these, 600 people were randomly selected, to provide approximately the same number of each gender for the baseline survey. Participants were asked to sign consent forms regarding the protocol, which was approved by the Ethics Committee of Niigata University School of Dentistry.

Participants were assessed according to the TMIG-Index of Competence subscale questionnaires. The TMIG-Index of Competence is used to assess functional capacity in older persons. The ability to perform a given function is indicated by `Yes’ or `No’. The highest score on the TMIG-Index subscales is 13 (Koyano et al., 1991). The mean score of the TMIG-Index subscales of participants in this study was 11.9 ± 1.4. The results of this assessment pointed to a high level of competence among participants in this study.

Dental examinations were carried out at baseline and once a year for 6 yrs (1998–2004), that is, 7 times in 6 yrs.

Measurements
Root Caries Events
Four trained and experienced dentists assessed dental caries, including root caries. The examinations were conducted with the use of mirrors and ball-point periodontal probes under artificial light, without bite-wing radiographs. Root caries was diagnosed based on the criteria of the World Health Organization (1997). First, it was determined whether a given surface was exposed or not. An exposed root surface was defined as having at least 1 mm of visible root surface between the gingival crest and the cemento-enamel junction or the restoration margin. All exposed root surfaces were examined and recorded. Root decay was defined as a lesion detected on an exposed root surface that felt soft or leathery when probed. For a single instance of decay affecting both the crown and the root, the likely site of origin of the lesion was recorded as "decayed". When it was not possible to judge the site of origin, both the crown and the root were recorded as "decayed".

We tracked root caries incidence only on surfaces that were neither decayed nor filled at baseline examination. Whenever root decay was detected on a root surface that had previously been sound or non-exposed, it was counted as a disease event. Disease events were counted each year. Surfaces where disease events occurred once were excluded from additional-year evaluations. Finally, the number of surfaces on which a disease event occurred over the 6 yrs was converted into the number of teeth on which a disease event occurred in a given participant.

Interexaminer reliability for surfaces was assessed for the four examiners using 18 volunteer patients in the University Hospital before and during the survey. We calculated a kappa score using 5 codes (Sound, Filled, Decayed, Filled [with decay], and Bridge abutment: Special crown or Veneer/implant). The kappa values between each pair of examiners were 0.84–0.97.

Periodontal Disease Events
The periodontal examination included the assessment of attachment level at 6 sites around each tooth. Probing was performed with the use of a pressure-constant probe (Vivacare TPS Probe®, Schaan, Liechtenstein) and a probing force of 20 g. The periodontal examination was carried out by four trained dentists under sufficient illumination using artificial light. At first, the difference between attachment level at baseline and at follow-up for each site was calculated with site-level data. If the difference was ≥ 3 mm, it was counted as a periodontal disease event. Surfaces where disease events occurred once were excluded from additional-year assessments. Data were rounded off from site-level to tooth-level. Finally, the number of teeth with an event per person was calculated.

Interexaminer reliability for attachment was assessed for the four examiners using 18 volunteer patients in the University Hospital before and during the survey. As determined by replicate examinations of attachment level, the percent agreement (± 1 mm) ranged from 70.0% to 100%. The kappa (± 1 mm) ranged from 0.62 to 1.00.

Composition and Blood Measurements
Anthropometric evaluation included measurements of weight and height for the calculation of body mass index (BMI). BMI is defined as the individual’s body weight divided by the square of his/her height. In addition, serum albumin and immunoglobulin G (IgG) concentrations were measured at a commercial laboratory (BML, Inc., Tokyo, Japan). Serum albumin concentration ≤ 4.0 g/dL was defined as low according to a previous report (Phillips et al., 1989).

Statistical Analysis
For descriptive data (BMI, serum IgG levels, and the number of periodontal disease events), statistical differences between the number of root caries events were evaluated by analysis of variance (ANOVA) and Scheffé’s multiple comparison test for the individuals with instances with zero root caries. Means and standard deviations were used to characterize continuous variables. In addition, we compared the number of root caries events over 6 yrs between persons with serum albumin concentrations ≤ 4.0 g/dL at baseline and those of persons with serum albumin concentrations > 4.0 g/dL at baseline, using the paired Student’s t test. Subsequently, we selected persons with serum albumin concentrations > 4.0 g/dL at baseline and divided them into two groups: those with serum albumin concentrations ≤ 4.0 g/dL after 6 yrs and those with serum albumin concentrations > 4.0 g/dL after 6 yrs. We then compared the number of root caries events between these two groups.

Finally, we performed multiple linear regression analysis to assess the relationship between changes in serum albumin concentrations and the number of root caries events over 6 yrs, after controlling for periodontal disease events over 6 yrs, changes in BMI over 6 yrs, changes in serum IgG concentrations over 6 yrs, gender, the remaining number of teeth at baseline, the number of sites with ≥ 4 mm attachment level at baseline, and the number of decayed and filled surfaces at baseline. The level of significance was set at p < 0.05 for these tests. All calculations and statistical analyses were performed with the STATATM software package (Stata Corp., College Station, TX, USA).


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In this study, 334 people dropped out during the study. Serum albumin concentrations at baseline were 4.3 ± 0.2 g/dL for study participants and 4.3 ± 0.3 g/dL for the group who dropped out during the study. There was no significant difference between the two groups (p = 0.168; Student’s t test). In addition, 36 people died during the study. Serum albumin concentrations at baseline for these persons were 4.1 ± 0.3 g/dL. The difference in serum albumin concentrations at baseline between study participants and those who died during the study was statistically significant (p < 0.001; Student’s t test).

Of 600 participants, 266 persons who had at least 1 tooth at baseline and participated in all annual investigations (7 times in total), from baseline to 6 yrs, were included in the analysis. Baseline characteristics of the participants were: serum albumin levels, 4.3 ± 0.2 g/dL; serum IgG levels, 1483.9 ± 288.2 mg/dL; BMI, 22.4 ± 2.9 kg/m2; the number of remaining teeth, 19.4 ± 8.2; the number of untreated and treated surfaces, 2.3 ± 3.2; and the number of sites with ≥ 4 mm attachment levels, 29.1 ± 25.7. Root caries developed in 52.3% of the participants over the six-year study. Serum IgG concentrations and periodontal disease events showed significantly high values, with an increase in root caries events assessed by ANOVA (p = 0.013 for serum IgG; p = 0.007 for periodontal disease events). However, these differences were not significant according to the Scheffé multiple comparison test for the participants with instances with zero root caries (Table 1Go).


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Table 1. Distribution of Root Caries Events and Association with Changes in BMI, IgG, and Periodontal Disease Events over 6 yrs (1998–2004)
 
In addition, persons with lower serum albumin concentrations (≤4.0 g/dL) at baseline had a significantly higher number of root caries events over 6 yrs compared with persons with high serum albumin concentrations (> 4.0 g/dL) at baseline (1.8 ± 2.2 vs. 1.1 ± 1.6, respectively; p = 0.031, Student’s t test) (Fig. 1Go). We divided persons with serum albumin concentrations > 4.0 g/dL at baseline into two groups: those with serum albumin concentrations ≤ 4.0 g/dL after 6 yrs and those with serum albumin concentrations > 4.0 g/dL after 6 yrs. The mean number of root caries events for 6 yrs was 1.6 ± 2.1 for the persons with serum albumin concentrations ≤ 4.0 g/dL after 6 yrs, compared with 1.0 ± 1.4 for those with serum albumin concentrations > 4.0 g/dL after 6 yrs (p = 0.009, Student’s t test) (Fig. 2Go).


Figure 1
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Figure 1. Number of root caries events based on serum albumin concentrations at baseline.

 

Figure 2
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Figure 2. Number of root caries events based on serum albumin concentrations after 6 yrs. Subjects with serum albumin concentrations > 4.0 g/dL at baseline and with serum albumin concentrations ≤ 4.0 g/dL after 6 yrs: n = 52. Subjects with serum albumin concentrations > 4.0 g/dL at baseline and with serum albumin concentrations > 4.0 g/dL after 6 yrs: n = 180. Subjects with serum albumin concentrations ≤ 4.0 g/dL at baseline and with serum albumin concentrations ≤ 4.0 g/dL after 6 yrs: n = 20. Subjects with serum albumin concentrations ≤ 4.0 g/dL at baseline and with serum albumin concentrations > 4.0 g/dL after 6 yrs: n = 14.

 
According to the results of multiple regression analysis, the number of root caries events, the change in BMI, serum IgG concentrations over 6 yrs, gender, and the number of sites with ≥ 4 mm attachment level at baseline were significantly associated with the change in serum albumin concentrations over 6 yrs (Table 2Go).


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Table 2. Relationship between the Number of Root Caries Events and Change in Serum Albumin Concentration over 6 yrs by Multiple Regression Analysise
 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
There was no significant difference in serum albumin concentrations at baseline between the study participants and those who dropped out. Therefore, we thought that the participants in this study were representative of the community. In addition, serum albumin concentrations ≤ 4.0 g/dL were defined as low according to Phillips’ report (Phillips et al., 1989). In the latter report, serum albumin concentrations were divided into 6 categories (< 4.0, 4.0-, 4.2-, 4.4-, 4.6-, 4.8-). There was a gradual increase in mortality rate with decreasing serum albumin concentrations. Persons with serum albumin levels < 4.0 g/dL had a crude all-cause mortality rate 6 times that of persons with a serum albumin concentration of 4.8 g/dL or higher. Therefore, we designated serum albumin concentrations as low (≤4.0 g/dL) and high (> 4.0 g/dL) in this study.

To our knowledge, this is the first longitudinal study to clarify the relationship between root caries and serum albumin levels in elderly persons. In this study, the number of root caries events over 6 yrs was significantly associated with the change in serum albumin concentrations over this period, after adjustment for confounding factors by multiple regression analysis. The standardized coefficient of the number of root caries events was –0.148 (p = 0.024). We can confirm that serum albumin concentration correlates with root caries events. Accordingly, these longitudinal findings support the results of a previous cross-sectional study indicating an association between oral health status and serum albumin levels (Yoshihara et al., 2003).

Serum albumin levels provide an index of the severity of an underlying disease. Many conditions, such as malnutrition, inflammatory disorders, liver disease, and renal diseases, reduce serum albumin levels. In these cases, persons with hypoalbuminemia and malnutrition are likely to have decreased immunocompetence, with an increased risk of infection (Goubran Botros et al., 1996).

In our study, the root caries events showed a direct relationship with increasing levels of IgG. In addition, a statistically significant association was found between IgG and serum albumin. Serum albumin concentrations fall as a result of a variety of infections. According to previous reports, serum IgG levels increase with the presence of dental caries (Parkash et al., 1994; de Soet et al., 2003). The nature of the human immune response to dental caries suggests that Streptococcus mutans and serum antibodies may play a major role in the pathogenesis of dental caries (Chia et al., 2000). Furthermore, there was a significant relationship between serum albumin and serum IgG levels (Goubran Botros et al., 1996).

Individuals with high root caries experience (> 7) had more periodontal disease events in our study than those with zero root caries, even if it was not significant by Scheffé’s multiple comparison test. According to our previous study, having 1 or more instances of root caries was significantly associated with a mean loss of attachment (Takano et al., 2003). Gingival recession or pocket depth was reported as a risk predictor or risk marker for root caries (Lawrence et al., 1995; Mack et al., 2004). Most lesions occurred on exposed root surfaces.

In this study, BMI was a significant factor associated with serum albumin levels (standardized coefficient, 0.177; p = 0.004) by multiple regression analysis, though there was no significant relation between root caries events and changes in BMI. According to a previous report, even if BMI or albumin levels were lower in the edentulous than in the dentate group, caries was not related to malnutrition (Mojon et al., 1999). Our results support this previous finding.

We conclude that persons with hypoalbuminemia are at high risk for root caries. Furthermore, it is possible that root caries may influence the immune response in the elderly.


    ACKNOWLEDGMENTS
 
This work was supported by a Grant-in-Aid from the Ministry of Health and Welfare of Japan (H 16-Iryo-001), and from the Ministry of Education, Science, Sports and Culture of Japan (Grant No. 17592177).

Received for publication April 2, 2006. Revision received June 4, 2007. Accepted for publication June 5, 2007.


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  • Baumgartner RN, Koehler KM, Romero L, Garry PJ (1996). Serum albumin is associated with skeletal muscle in elderly men and women. Am J Clin Nutr 64:552–558.[Abstract/Free Full Text]
  • Chia JS, Chang WC, Yang CS, Chen JY (2000). Salivary and serum antibody response to Streptococcus mutans antigens in humans. Oral Microbiol Immunol 15:131–138.[Medline] [Order article via Infotrieve]
  • Corti MC, Guralnik JM, Salive ME, Sorkin JD (1994). Serum albumin level and physical disability as predictors of mortality in older persons. J Am Med Assoc 272:1036–1042.[Abstract/Free Full Text]
  • de Soet JJ, Schriks MC, Kratz E, Poland DC, van Dijk W, van Amerongen WE (2003). Dental caries related to plasma IgG and alphal-acid glycoprotein. Caries Res 37:79–84.[Medline] [Order article via Infotrieve]
  • Don BR, Kaysen G (2004). Serum albumin: relationship to inflammation and nutrition. Semin Dial 17:432–437.[CrossRef][Medline] [Order article via Infotrieve]
  • Giordano M, De Feo P, Lucidi P, DePascale E, Giordano G, Cirillo D, et al. (2001). Effects of dietary protein restriction on fibrinogen and albumin metabolism in nephrotic patients. Kidney Int 60:235–242.[CrossRef][Medline] [Order article via Infotrieve]
  • Goubran Botros H, Gregoire C, Rabillon J, David B, Dandeu JP (1996). Cross-antigenicity of horse serum albumin with dog and cat albumins: study of three short peptides with significant inhibitory activity towards specific human IgE and IgG antibodies. Immunology 88:340–347.[Medline] [Order article via Infotrieve]
  • Herrmann FR, Safran C, Levkoff SE, Minaker KL (1992). Serum albumin level on admission as a predictor of death, length of stay, and readmission. Arch Intern Med 152:125–130.[Abstract/Free Full Text]
  • Koyano W, Shibata H, Nakazato K, Raga H, Suyama Y (1991). Measurement of competence: reliability and validity of the TMIG Index of Competence. Arch Gerontol Geriatr 13:103–116.[Medline] [Order article via Infotrieve]
  • Lawrence HP, Hunt RJ, Beck JD (1995). Three-year root caries incidence and risk modeling in older adults in North Carolina. J Public Health Dent 55:69–78.[Medline] [Order article via Infotrieve]
  • Locker D, Ford J, Leake JL (1996). Incidence of and risk factors for tooth loss in a population of older Canadians. J Dent Res 75:783–789.
  • Mack F, Mojon P, Budtz-Jorgensen E, Kocher T, Splieth C, Schwahn C, et al. (2004). Caries and periodontal disease of the elderly in Pomerania, Germany: results of the Study of Health in Pomerania. Gerodontology 21:27–36.[Medline] [Order article via Infotrieve]
  • Magagnotti C, Orsi F, Bagnati R, Celli N, Rotilio D, Fanelli R, et al. (2000). Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) in humans. Int J Cancer 88:1–6.[Medline] [Order article via Infotrieve]
  • Mattila KJ, Valtonen VV, Nieminen M, Huttunen JK (1995). Dental infection and the risk of new coronary events: prospective study of patients with documented coronary artery disease. Clin infect Dis 20:588–592.[Medline] [Order article via Infotrieve]
  • Mojon P, Budtz-Jorgensen E, Rapin CH (1999). Relationship between oral health and nutrition in very old people. Age Ageing 28:463–468.[Abstract/Free Full Text]
  • Parkash H, Sharma A, Banerjee U, Sidhu SS, Sundaram KR (1994). Humoral immune response to mutans streptococci associated with dental caries. Natl Med J India 7:263–266.[Medline] [Order article via Infotrieve]
  • Phillips A, Shaper AG, Whincup PH (1989). Association between serum albumin and mortality from cardiovascular disease, cancer, and other causes. Lancet 16:1434–1436.
  • Powell LV, Leroux BG, Persson RE, Kiyak HA (1998). Factors associated with caries incidence in an elderly population. Community Dent Oral Epidemiol 26:170–176.[Medline] [Order article via Infotrieve]
  • Rigaud D, Hassid J, Meulemans A, Poupard AT, Boulier A (2000). A paradoxical increase in resting energy expenditure in malnourished patients near death: the king penguin syndrome. Am J Clin Nutr 72:355–360.[Abstract/Free Full Text]
  • Scheinin A, Pienihakkinen K, Tiekso J, Holmberg S, Fukuda M, Suzuki A (1994). Multifactorial modeling for root caries prediction: 3-year follow-up results. Community Dent Oral Epidemiol 22:126–129.[Medline] [Order article via Infotrieve]
  • Shibata H, Naga H, Ueno M, Nagai H, Yasumura S, Koyano W (1991). Longitudinal changes of serum albumin in elderly people living in the community. Age Ageing 20:417–420.[Abstract/Free Full Text]
  • Takano N, Ando Y, Yoshihara A, Miyazaki H (2003). Factors associated with root caries incidence in an elderly population. Community Dent Health 20:217–222.[Medline] [Order article via Infotrieve]
  • Tenovuo J, Lehtonen OP, Aaltonen AS (1990). Caries development in children in relation to the presence of mutans streptococci in dental plaque and of serum antibodies against whole cells and protein antigen I/II of Streptococcus mutans. Caries Res 24:59–64.[Medline] [Order article via Infotrieve]
  • Walrand S, Chambon-Savanovitch C, Felgines C, Chassagne J, Raul F, Normand B, et al. (2000). Aging: a barrier to renutrition? Nutritional and immunologic evidence in rats. Am J Clin Nutr 72:816–824.[Abstract/Free Full Text]
  • World Health Organization (1997). Oral Health Surveys: basic methods. 4th ed. Geneva: World Health Organization, pp. 21–52.
  • Yoshihara A, Hanada N, Miyazaki H (2003). Association between serum albumin and root caries in community-dwelling older adults. J Dent Res 82:218–222.

Journal of Dental Research, Vol. 86, No. 11, 1115-1119 (2007)
DOI: 10.1177/154405910708601118


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This Article
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