|Year : 2013 | Volume
| Issue : 1 | Page : 10-15
Association of environmental cadmium exposure and periodontal disease
Amitha Ramesh, Anju Mary John, Biju Thomas, Rahul Bhandary
Department of Periodontics, A. B. Shetty Memorial Institute of Dental Sciences, Derlakatte, Mangalore, Karnataka, India
|Date of Web Publication||26-Nov-2013|
Anju Mary John
Department of Periodontics, A. B. Shetty Memorial Institute of Dental Sciences, Derlakatte, Mangalore - 575 018, Karnataka
Source of Support: None, Conflict of Interest: None
Background and Aims: Cadmium adversely affects bone remodeling and is therefore possible that environmental cadmium exposure may be a risk factor for periodontal disease-related bone loss. Aim of the present study was to assess the association between environmental cadmium exposure and periodontal disease. Settings and Design: The study was conducted in the Department of Periodontics, in our institution, Mangalore and sample size consisted of 100 patients (two groups of 50 patients each). Materials and Methods: Gingival Index, periodontal probing depth and clinical attachment loss was estimated to ascertain the gingival and periodontal status of subjects. Urine samples were collected from the subjects and biochemical analysis was done to estimate urine cadmium levels. Statistical Analysis: Results obtained were then statistically analyzed using Mann-Whitney U-test and correlation was done using Karl Pearson's correlation. Results: There was an increased concentration of urinary cadmium in periodontitis patients when compared with the healthy controls and there was a positive correlation between age and cadmium concentrations. Conclusion: Although information on the oral health effects of cadmium remains limited, the results of this study suggests that cadmium exposure may be an important risk factor for periodontal disease in adults.
Keywords: Cadmium exposure, inflammation, periodontal disease
|How to cite this article:|
Ramesh A, John AM, Thomas B, Bhandary R. Association of environmental cadmium exposure and periodontal disease. Int J Oral Health Sci 2013;3:10-5
| Introduction|| |
Periodontal disease is a complex, multi-factorial, chronic inflammatory disease that involves degradation of periodontal structures, including alveolar bone.  Although environmental factors have been implicated as possible risk factors, the role of environmental toxins in the etiology of this disease has received limited attention.  Cadmium is a ubiquitous toxicant in our environment. Human exposure to cadmium is possible from the number of sources, with smoking being a major contributor. Other sources of cadmium include emissions from industrial activities, including mining, smelting, fuel combustion, application of municipal sludge or phosphate fertilizer and manufacturing of batteries, pigments, stabilizers and alloys. Human exposure to cadmium is primarily through food, with low levels of cadmium found in all foods. 
Due to its high rates of soil-to-plant transport; cadmium is a contaminant found in most foodstuffs, which renders diet a primary source of exposure among non-smoking, non-occupationally exposed populations.  The pathologic effect of cadmium on bone, including the ability to promote inflammation, are pertinent to periodontal disease. Cadmium adversely affects bone remodeling and is therefore possible that environmental cadmium exposure may be a risk factor for periodontal disease-related bone loss. Hence, this study was designed to assess the association of environmental cadmium exposure and periodontal disease.
| Materials and Methods|| |
The samples were selected from the patients reported to the Department of Periodontics, out of which 100 patients fulfilled the inclusion criteria. Medical history and dental history of the subjects were determined prior to inclusion into the study and control groups.
Subjects were informed and assured about the confidentiality of the research findings and of the report. After obtaining ethical clearance from institutions ethics committee, informed consent was taken from the subjects. The subjects were randomly divided into two groups: Group A-50 subjects with healthy periodontium aged between 35 and 55 years and Group B - 50 subjects with chronic periodontitis with clinical attachment loss of >4 mm in greater than 30% of the sites examined, aged between 35 and 55 years.
Full mouth periodontal examination of the 100 study participants were performed by a single examiner. Clinical measurements of periodontal disease were done for all the present teeth in which periodontal pocket depth on six sites per tooth (mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual, distolingual) were recorded and clinical attachment loss and gingival index (Loe and Silness, 1963) were calculated. The present study focused the analysis on clinical attachment loss, which is a measure of periodontal tissue lost because of the disease process. Clinical attachment was taken as the distance from the cemento-enamel junction to the base of the sulcus measured using Williams graduated periodontal probe. This distance was calculated by subtracting the distance from the gingival margin to the cemento-enamel junction from the pocket depth. Attachment loss of >4 mm in greater than 30% of the sites examined were used as a case definition of periodontitis.
Urinary cadmium and creatinine measurements
A total volume of 10 ml sample of midstream urine was collected from the study participants. Cadmium was quantified by Zeeman effect graphite furnace atomic absorption spectrophotometer with a detection limit of approximately 0.01 ng/ml.  Urinary creatinine was obtained from the same urine specimen and measured in ml/dl. Quality control procedures call for urine specimens to be processed, stored and transported to the research laboratory for analysis as per National Center for Health Statistics quality control protocol.  A creatinine-adjusted urinary cadmium measure (μg/g) was generated by dividing urinary cadmium (ng/ml) by urinary creatinine (ml/dl). 
For estimation of creatinine corrected urinary cadmium concentration, the urine sample was first digested with concentrated nitric acid. The sample was then analyzed with the help of Zeeman effect graphite furnace atomic absorption spectrophotometer for the estimation of urinary cadmium level.
The values obtained were tabulated, mean and standard deviation calculated [Table 1]. Threshold of significance was set at when P < 0.05. Test of normality was done using Shapiro-Wilk test to determine the distribution of the parameters and the results showed that the parameters follow a non-linear distribution. Because of the non-linear distribution of the parameters, Mann-Whitney U-test, a non-parametric test was selected for further analysis. Correlation between age and cadmium levels in the entire study population and in test and control group separately was done using Karl Pearson Correlation. In the present study, statistical evaluation was performed using "R 2.15" statistical software.
| Results|| |
The median creatinine corrected urine cadmium concentration of the participants in the control group was 0.39 μg/g of creatinine, with the 25 th and the 75 th percentiles being 0.31 and 0.495 μg/g of creatinine respectively [Table 2]. Whereas, in the test group, the median value of creatinine corrected urine cadmium concentration was 0.65 μg/g of creatinine, with the 25 th and 75 th percentiles being 0.51 and 0.85 μg/g of creatinine [Chart 1]. [Additional file 1] This shows that there was an increased concentration of urinary cadmium in periodontitis patients when compared to the healthy controls which was statistically significant (P < 0.001). Correlation between age and creatinine corrected urinary cadmium levels in the entire study population was done [Table 3]. The results showed that there is a positive correlation, which is significant at the 0.01 level [Chart 2] [Additional file 2].
|Table 2: Correlation of creatinine corrected urine cadmium concentration in Cases and Controls|
Click here to view
Correlation between age and creatinine corrected urinary cadmium levels were done in the test group and control group separately [Table 4]. The results showed that there is a significant positive correlation in individuals of both the control group and the periodontitis group. In the present study, with age, there was a statistically significant increase (P < 0.001) in cadmium concentration in both the test group and the control group.
| Discussion|| |
Periodontitis is a term used to describe an inflammatory process, initiated by the plaque bio-film, that leads to the loss of periodontal attachment to the root surface and adjacent alveolar bone and which ultimately results in tooth loss.  There is an essential bacterial etiology and there are specific periodontal pathogens associated with destructive periodontal diseases. However, these pathogens do not invariably cause disease simply by their presence alone.  Environmental factors have been implicated as possible risk factors in altering periodontal disease expression. However, limited research have been conducted in determining the role of environmental toxins like cadmium in the etiology and pathogenesis of periodontal disease. 
Cadmium is one of the most toxic metals to which man can be exposed at work or in the environment. , Cadmium is primarily toxic to the proximal tubular cells where it selectively accumulates over time and may cause irreversible damage. Recent studies indicate that relatively low exposure to cadmium may also affect the skeletal tissues, , but the relationship is not well-documented. Primary source of human exposure to cadmium is through food with all foods containing low levels of cadmium.  Cadmium accumulates in the human body, particularly in the kidney, where it can remain for many years. A small portion of cadmium is slowly excreted in urine.  In people with low exposures; urinary cadmium is a biomarker for lifetime cadmium body burden. 
The objective of this study was to evaluate the association between environmental cadmium exposures, as measured by creatinine corrected urinary cadmium level and periodontal disease in the adult population. In the present study, it was found that environmental cadmium exposure, as measured by creatinine - corrected urine cadmium concentration, was associated with increased odds of prevalent periodontal disease. In examining this association, smoking and several other established risk factors for periodontal disease that may potentially confound its observed relation to cadmium exposure was adjusted.
The findings of this study are supported by the known effects of cadmium exposure on bone and other tissues. Chronic low level cadmium exposure has been linked to decreased bone mineral density and osteoporosis in a number of epidemiological studies. ,, These results have been confirmed in animal experiments where administration of low levels of cadmium over periods of up to 24 months resulted in decreased bone mineral density and increased incidence of osteoporosis.  In these experiments, the serum concentration of telopeptide of type I collagen, a marker of bone resorption, was increased, whereas the activity of serum alkaline phosphatase, a marker of bone formation was decreased, indicating a disturbance of normal bone metabolism due to cadmium exposure.
Data from a number of laboratory experiments suggests that inflammatory mediators, such as prostanoids, cytokines and matrix metalloproteinases, may be responsible for these effects. In vitro experiments have shown that cadmium exposure stimulates the production of prostaglandin E2 in osteoblast-like cells. 
The available evidence suggests that cadmium may further aggravate disturbances in the bone remodeling process that are present in periodontal disease. Given the important role of inflammation in periodontal disease, it is plausible that environmental factors, such as exposure to cadmium, that stimulate the release of inflammatory mediators may contribute to periodontal disease-related tissue destruction. 
Tobacco smoke contains many chemicals that may elevate the risk of periodontal disease.  Tobacco smoke is a major source of adult exposure to cadmium.  So particular emphasis was placed on distinguishing the relationship between cadmium and periodontitis from effects of smoking. Analysis for cigarette smoking was adjusted using self-reported smoking behavior and questionnaire recorded responses in order to identify participants with exposure to cigarette smoke in their home and workplace. The relationship between urinary cadmium and periodontal disease remained significant after considering all these variables. Without the inclusion of all tobacco variables in the present analyses, the association between urinary cadmium and periodontal disease was notably stronger [Table 3]. The results of this study was in accordance with the large cross-sectional study conducted to determine the association of environmental cadmium exposure with periodontal disease in U.S. adults. 
Furthermore, it was a concern that tobacco exposure may contain several risk factors for periodontal disease that may partially compete with cadmium, obscuring the observed association between cadmium and periodontal disease among tobacco users and those exposed to high levels of environmental tobacco smoke. It is possible that among these individuals, other constituents of tobacco smoke may promote the development of periodontal disease to such an extent that cadmium exposure no longer has a substantial impact on risk.
This finding is in accordance with the findings of the cross-sectional study conducted by Arora et al.  The results of several cross-sectional and epidemiological studies ,, also showed an increased concentration of urinary cadmium with age. Population based studies in Europe has shown that low to moderate exposure to cadmium has been associated with a decrease in bone density, an increased risk of bone fractures and height loss in women and men respectively. , In population-based studies conducted in China, forearm bone density was shown to decrease linearly with age and urinary cadmium in both sexes, suggesting a dose effect relationship between cadmium dose and bone mineral density. A marked increase in the prevalence of fractures was shown in the cadmium-polluted area in both sexes. ,
This study is limited primarily by its cross-sectional design, which prevents the establishment of a temporal relationship between cadmium exposure and periodontal disease. However, the use of urinary cadmium which is a marker of long-term exposure, allowed the consideration of the effects of cadmium exposure over periods on the order of a decade or longer.  Furthermore, it is unlikely that reverse causality (periodontal disease affecting the levels of cadmium in urine) is responsible for observed findings. In cross-sectional studies that include older adults, survival to be in cohort may be influenced by the exposure of interest; if cadmium exposure increases the risk of mortality,  any resulting bias in the findings of this study would likely be toward underestimating cadmium's association with periodontal disease.
Although this study was strengthened by the use of detailed measures of a number of important covariates, including exposure to tobacco smoke, unmeasured or mis-measured variables and relatively small sample size may have confounded the observed association between environmental cadmium exposure and periodontal disease. The results of this study suggest that environmental cadmium exposure may be an important risk factor for periodontal disease in the general population. However, the appropriate mechanism behind this association is not completely understood.
| Conclusion|| |
The findings of this study showed that environmental cadmium exposure, as measured by creatinine - corrected urine cadmium concentration, was associated with increased odds of periodontal disease, which was statistically significant and there was statistically significant increase in urinary cadmium concentration with increasing age, irrespective of the case and the controls.
Widespread exposure and increasing evidence of systemic health effects make environmental cadmium exposure a significant public health issue. Although information on the oral health effects of this toxic environmental pollutant remains limited, the results of this study suggest that cadmium exposure may be an important risk factor for periodontal disease in adults. In order to explore the actual relationship between periodontal disease status and environmental cadmium exposure and to elucidate the mechanism behind this association, further prospective studies and controlled clinical trials will be necessary.
| References|| |
|1.||Preshaw PM, Seymour RA, Heasman PA. Current concepts in periodontal pathogenesis. Dent Update 2004;31:570-2, 574. |
|2.||Barbour SE, Nakashima K, Zhang JB, Tangada S, Hahn CL, Schenkein HA, et al. Tobacco and smoking: Environmental factors that modify the host response (immune system) and have an impact on periodontal health. Crit Rev Oral Biol Med 1997;8:437-60. |
|3.||Satarug S, Baker JR, Urbenjapol S, Haswell-Elkins M, Reilly PE, Williams DJ, et al. A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett 2003;137:65-83. |
|4.||Järup L. Hazards of heavy metal contamination. Br Med Bull 2003;68:167-82. |
|5.||NCHS. NHANES III Laboratory Data File Documentation; The Third National Health and Nutrition Examination Survey, NHANES III (1988-94). Hyattsville, MD: National Centre for Health Statistics, Centers for Disease Control and Prevention; 2006. |
|6.||Claeys F, Ducoffre G, Sartor F, Roels H. Analytical quality control of cadmium and lead in blood and cadmium in urine: results of its implementation during a five-year epidemiological study. IARC Scientific Publications; 1992. p. 83-92 |
|7.||Staessen JA, Kuznetsova T, Roels HA, Emelianov D, Fagard R. Exposure to cadmium and conventional and ambulatory blood pressures in a prospective population study. Public Health and Environmental Exposure to Cadmium Study Group. Am J Hypertens 2000;13:146-56. |
|8.||Ogawa H, Yoshihara A, Amarasena N, Hirotomi T, Miyazaki H. Association between serum albumin and periodontal disease in community-dwelling elderly. J Clin Periodontol 2006;33:312-6. |
|9.||Löe H. Periodontal diseases: A brief historical perspective. Periodontol 2000 1993;2:7-12. |
|10.||Schutte R, Nawrot TS, Richart T, Thijs L, Vanderschueren D, Kuznetsova T, et al. Bone resorption and environmental exposure to cadmium in women: A population study. Environ Health Perspect 2008;116:777-83. |
|11.||Bernard A. Renal dysfunction induced by cadmium: Biomarkers of critical effects. Biometals 2004;17:519-23. |
|12.||Kjellström T. Mechanism and epidemiology of bone effects of cadmium. IARC Sci Publ 1992;15:301-10. |
|13.||Staessen JA, Roels HA, Emelianov D, Kuznetsova T, Thijs L, Vangronsveld J, et al. Environmental exposure to cadmium, forearm bone density, and risk of fractures: Prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group. Lancet 1999;353:1140-4. |
|14.||Alfvén T, Elinder CG, Hellström L, Lagarde F, Järup L. Cadmium exposure and distal forearm fractures. J Bone Miner Res 2004;19:900-5. |
|15.||ATSDR. Draft Toxicological Profile for Cadmium. Atlanta, GA: Agency for Toxic Substances and Disease Registry; 1999. |
|16.||Honda R, Tsuritani I, Noborisaka Y, Suzuki H, Ishizaki M, Yamada Y. Urinary cadmium excretion is correlated with calcaneal bone mass in Japanese women living in an urban area. Environ Res 2003;91:63-70. |
|17.||Alfvén T, Elinder CG, Carlsson MD, Grubb A, Hellström L, ersson B, et al. Low-level cadmium exposure and osteoporosis. J Bone Miner Res 2000;15:1579-86. |
|18.||Arora M, Weuve J, Schwartz J, Wright RO. Association of environmental cadmium exposure with periodontal disease in U.S. adults. Environ Health Perspect 2009;117:739-44. |
|19.||Brzóska MM, Moniuszko-Jakoniuk J. Low-level lifetime exposure to cadmium decreases skeletal mineralization and enhances bone loss in aged rats. Bone 2004;35:1180-91. |
|20.||Suzuki Y, Morita I, Ishizaki Y, Yamane Y, Murota S. Cadmium stimulates prostaglandin E2 synthesis in osteoblast-like cells, MC3T3-E1. Biochim Biophys Acta 1989;1012:135-9. |
|21.||Mortensen ME, Wong LY, Osterloh JD. Smoking status and urine cadmium above levels associated with subclinical renal effects in U.S. adults without chronic kidney disease. Int J Hyg Environ Health 2011;214:305-10. |
|22.||Lauwerys RR, Bernard AM, Roels HA, Buchet JP. Cadmium: Exposure markers as predictors of nephrotoxic effects. Clin Chem 1994;40:1391-4. |
|23.||Olsson IM, Bensryd I, Lundh T, Ottosson H, Skerfving S, Oskarsson A. Cadmium in blood and urine - Impact of sex, age, dietary intake, iron status, and former smoking - Association of renal effects. Environ Health Perspect 2002;110:1185-90. |
|24.||Akesson A, Bjellerup P, Lundh T, Lidfeldt J, Nerbrand C, Samsioe G, et al. Cadmium-induced effects on bone in a population-based study of women. Environ Health Perspect 2006;114:830-4. |
|25.||Gallagher CM, Kovach JS, Meliker JR. Urinary cadmium and osteoporosis in U.S. Women > or = 50 years of age: NHANES 1988-1994 and 1999-2004. Environ Health Perspect 2008;116:1338-43. |
|26.||Nordberg G, Jin T, Bernard A, Fierens S, Buchet JP, Ye T, et al. Low bone density and renal dysfunction following environmental cadmium exposure in China. Ambio 2002;31:478-81. |
|27.||Wang H, Zhu G, Shi Y, Weng S, Jin T, Kong Q, et al. Influence of environmental cadmium exposure on forearm bone density. J Bone Miner Res 2003;18:553-60. |
|28.||Nawrot TS, Van Hecke E, Thijs L, Richart T, Kuznetsova T, Jin Y, et al. Cadmium-related mortality and long-term secular trends in the cadmium body burden of an environmentally exposed population. Environ Health Perspect 2008;116:1620-8. |
[Table 1], [Table 2], [Table 3], [Table 4]