Saliva- A Tool for Diagnosis in Periodontal Disease

M. Abiramidevi; Visalakshi Nagappan; P. Arun Kumar Prasad

doi:10.18311/jade/2018/20883

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Review

4 (

); 1-7

doi:

10.18311/jade/2018/20883

Saliva- A Tool for Diagnosis in Periodontal Disease

M. Abiramidevi¹, Visalakshi Nagappan², P. Arun Kumar Prasad³

1Intern, Department of Periodontics, K.S.R Institute of Dental Science and Research, K. S. R Kalvi Nagar, Tiruchengode – 637215, Tamil Nadu, India, ksrdentalcollege@yahoo.co.in, doctorabi004@gmail.com

2Postgraduate Student, Department of Periodontics, K.S.R Institute of Dental Science and Research, K. S. R Kalvi Nagar, Tiruchengode – 637215, Tamil Nadu, India, ksrdentalcollege@yahoo.co.in, doctorabi004@gmail.com

3Professor, Department of Periodontics, K.S.R Institute of Dental Science and Research, K. S. R Kalvi Nagar, Tiruchengode – 637215, Tamil Nadu, India, ksrdentalcollege@yahoo.co.in, doctorabi004@gmail.com

*Author for correspondence

Received: 2018-03-01, Accepted: 2018-03-01, Published: 2018-06-30

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This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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This article was originally published by Informatics Publishing and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Periodontitis, a chronic inflammatory condition involving tooth supporting structures that results in connective tissue loss and progressive bone loss. Careful diagnosis and treatment plan is inevitable for the successful clinical outcome. Investigation of biomarkers specific to certain periodontal disease in saliva gains more clinical interest in the present era. The gratification towards saliva has been increased over GCF due to its ease and non-invasive methods of collection compared to GCF. Saliva contains numerous biomarkers which is an emerging chair side diagnostic tool that will play a major role for the future investigators. This article aims at reviewing the biomarkers present in the saliva pertaining to particular periodontal diseases and its activity.

Keywords

Periodontitis

Salivary Biomarkers

Salivary Enzymes

Show Related Articles from PubMed

1. Introduction

Successful periodontal therapy relays on early diagnosis and severity of a disease¹. Periodontitis, which is a most common periodontal disease category, is a irreversible inflammatory chronic condition that persuades to formation of probing pocket depth, progressive attachment loss, with loss of collagen fibres and can progress to bone loss if left untreated². Traditional diagnostic parameters fails to assess patients who are highly susceptible to periodontitis. The diagnostic use of saliva has attracted the attention of clinical investigators due to its non-invasiveness and ease of collection.

2. Emerging Diagnostic Tool-Saliva

Saliva plays a major role in lubrication, chewing, swallowing, digestion and protection of oral mucosa⁴. Local and general health of the human body is reflected as an essential biomarker in the saliva. Although gingival crevicular fluid plays a potential role in early diagnosis of periodontal disease progression³, the invasive and complex collecting procedure offers a technical challenge to the clinician.

3. Gratification of Saliva over Gingival Crevicular Fluid⁵

Painless collection process
Less distress to patient
Simple to collect and non-invasive
Convenient for multi sampling
Cost effective for screening large population
Cheap technology for laboratorial diagnosis
Easy to store
Less time consuming
Less blood contamination

4. Salivary Biomarkers in Periodontal Diseases

A biomarker is a substance used as an indicator for early disease detection and disease progression in diagnosis of oral diseases⁶. The bacterial products released during periodontal disease progression activate the immune response and triggers the various inflammatory cells such as polymorphonuclear neutrophils, monocytes, macrophages. Thus resulting in the release of various cytokines (prostaglandin E2, tumor necrosis factor and interleukins) and inflammatory markers in serum and saliva. Consequently the release of matrix metalloproteinases and collagen destructive enzymes leads to the extra cellular matrix degradation, a trespasser for periodontal disease progression.

The various salivary biomarkers² includes

Markers affecting dental biofilm
1. Specific marker
2. Non specific
Systemicbiomarkers to periodontal infection
Markers of periodontal soft tissue inflammation
Markers of alveolar bone loss
Salivary enzymes and ions
Growth factor as a salivary biomarker
Epithelial keratins
Hormones
Inflammatory cells and bacteria
Volatiles and oxidative stress marker

4.1 Markers Affecting Dental Biofilm

4.1.1 Specific Marker

Immunoglobulin interferes in adherence of bacterial metabolism in chronic and aggressive periodontitis. Increased concentration of immunoglobulin in patients with periodontitis has been clinically evident. Higher salivary constituents of various immunoglobulins such as IgA, IgG, IgM specific to certain periodontal pathogens are observed as a salivary parameter in patients with periodontitis compared to Non-periodontitis individuals. Especially, level of IgA has been greatly detected and their levels decreased significantly following non-surgical periodontal therapy.

4.1.2 Non Specific Biomarker (Table 1)

Table 1: Nonspecific biomarkers in periodontitis

Protein Markers	Nature of the Biomarker	Mechanism	Activity in Periodontitis
Mucins⁷	Glycoproteins(MG1,MG2) helps in maintaining the viscoelasticity of saliva	Interferes with attachment of A. actinomycetemcomitans	MG2 level declined in saliva with increased periodontal pathogens
Lactoferrin^2,7	Iron binding glycoprotein	Inhibit the growth of bacterial by lowering the iron content	i)Upregulated in gingival inflammation ii)Higher concentration in periodontal disease
Histatin^2,7	Salivary protein with antimicrobial properties	i) Neutralizes enzymes and lipopolysaccharides in gram negative bacteria ii) Inhibits the histamine expressed	Decreases the role of histamine
Fibronectin⁷	Glycoprotein	Improves the attachment and colonisation of bacteria	Additive role in repair and healing process
Cystatins⁷	Proteolytic enzyme released by bacteria inflammatory cells, osteoclast, fibroblast	Collagenolytic activity causing tissue destruction	Modulating enzyme activity in periodontium
Platelet Activating Factor (PAF)⁷	Stimulates the phospholipid and triggers the inflammation	Release of inflammatory mediators	Positive correlation between PAF and periodontal inflammation
Proline⁷	Amino acid	Degradation of amino acid	Both positive and negative correlation exist

4.2 Systemic Biomarker - C-Reactive Protein

Periodontal inflammation causes stimulation of circulatory cytokines such as tumour necrosis factor α, interleukin-1 which inturn induces the liver to produce C-reactive protein into the circulation. Salivary C-reactive protein is appreciated in chronic and aggressive periodontitis and act as inflammatory marker².

4.3 Markers Present in Inflamed Periodontium

Prostaglandin E2 is the major mediator of periodontal disease and act as a potent biomarker of soft tissue inflammation (figure 1). PGE2 stimulates the fibroblast and osteoblast to produce MMP’S which is again a potential biomarker of tissue destruction².

4.4 Markers Expressed in Alveolar Bone Loss

MMPs are responsible for tissue destruction and remodelling. Periodontal collagens are broken down by collagenases. MMP8 levels are most prevalent in active disease progression of patients with gingivitis and periodontitis. Also in patient with peri-implantitis the peri-implant sulcular fluid demonstrates an elevated level of MMP8. The need for future longitudinal studies in the salivary level of MMP8 in periodontitis patient is inevitable^2,7.

Gelatinase (MMP9) is a collagenase produced by neutrophils and has a pivotal role in degradation of collagenous intercellular ground substance. MMP9 increased in patients with periodontitis has been reported in the literature by Teng et al⁸.

Collagenase (MMP13) is another collagenolytic MMP found to be elevated in patients with periodontitis and peri-implantitis⁷.

Increase in concentration of telopeptide, osteocalcin, osteopontin in GCF of patients with progressive periodontal disease has been reported⁷.

4.5 Salivary Enzymes and Ions

The major salivary enzymes which act as potential biomarkers include lysozyme and peroxidase. Lysozymes are capable of breaking chemical bond in bacterial cell wall and hydrolyze the glycosidic linkages and distrupts the bacterial cell wall. Low level salivary lysozyme with high level of salivary peroxidase is considered as a factor for periodontal disease⁷.

Increased salivary calcium demonstrated in the saliva of patient with periodontal disease has been reported in the literature by Sewon et al⁹.

4.6 Growth Factor as a Salivary Biomarker

Growth factor act as remarkable biomarker in inflammation and wound healing. Higher levels of growth factor were detected in whole saliva of patient with periodontitis⁷.

4.7 Epithelial Keratins

Morgan et al., demonstrated the epithelial cells lining the mucosa can be demonstrated in patients saliva with periodontitis¹⁰.

4.8 Hormones

High salivary cortisol level has been demonstrated in patients with periodontitis along with emotional stress, poor oral hygiene, smoking⁷.

4.9 Inflammatory Cells and Bacteria

Increased orogranulocytic migration rate in the presence of oral inflammation has been reported by Raeste et al¹¹. Klinkhammer et al., developed the orogranulocytic migration rate¹².

Asikainen et al., Umeda et al., demonstrated the presence of microorganisms in the whole saliva¹³. Dejong et al., concluded saliva as a culture medium for Streptococcus and Actinomyces in his study¹⁴.

4.10 Volatiles and Oxidative Stress Marker

Hydrogen peroxide, methyl mercaptans are the known volatile sulphur compounds which act as a diagnostic marker in periodontal disease.

This results due to excessive free radicals or diminished antioxidant system. Oxidative stress leads to DNA damage including oxidation of nucleosides (8-hydroxy deoxy guanosine) which is a potent biomarker of oxidative stress. Biomarkers ellicited in periodontitis has been summarized in (Table 2).

Table 2. Summary of studies involving biomarkers in periodontitis

Authors	Aim	Outcome
Baltacioglu et al¹⁷	Evaluation of lipid peroxidation(malondialdehyde) level and total oxidant/antioxidant in patients serum and saliva	Salivary MDA level, TOS, TAOS are elevated in periodontitis group than control group
Priscila et al¹⁸	Compared the salivary concentration of matrix metalloproteinase 8, interleukin 6,osteoprotegrin in periodontitis patients with or without diabetes	Salivary IL-6 concentration is increased in both the groups while salivary MMP8 and OPG are elevated in patients with diabetes and periodontal inflammation
Ghallab et al¹⁹	Investigated the salivary soluble CD44 profiles of smoking and non-smoking patients with and without periodontitis in counter to SRT	Baseline salivary soluble CD44 elevated in smokers compared with non-smoking periodontitis group
Gursoy et al²⁰	Concentration of ICTP, MMP8, MMP14 and TIMP1 were analysed to detect potential markers of periodontitis	MMP8,MMP14,TIMP1 and ICTP are highly susceptible in advanced periodontitis patients
Al-Rawi et al²¹	Comparison of relationship between resist in and period onto pathogenic bacterial levels in obese adults, obese patients with type 2 diabetes and healthy controls	obese individuals with type 2 diabetes exhibited high level of salivary resist in
Nomura et al²²	Evaluated the level of alanine amino transferase,alkaline phosphatase and free haemoglobinas biomarker also the count of P. intermedia, P. gingivalis, T. forsythia in stimulated saliva	Low P. Gingivalis and ALT act as a potential indicator for the progression of periodontal disease
Bertl et al²³	Assessed the effect of non surgical periodontal therapy on salivary malotonin levels	Decreased salivary malotinin levels are the baseline which progressively increased at the end of the study
Novacovic et al²⁴	Investigated the impact of nonsurgical periodontal treatment and salivary antioxidants(albumins, uricacid, superoxide dismutase, glutathione peroxidase) and evaluated their capacity as a biomarker	All the clinical parameters except attachment level were remarkably decreased after SRP
Ramseier et al²⁵	Microbially derived biomarkers of plaque biofilm and saliva is determined	MMP-8,9and osteoprotegerin along with red-complex anaerobic bacteria were detected.
Miller et al²⁶	Conducted the study to determine the correspondence between periodontal disease and levels of IL-1ß, MMP8, OPG in saliva of patients with moderate to severe periodontitis	Salivary MMP8 and IL-1ß are visible to serve as biomarker of periodontal disease
Banasova et al²⁷	Compared oxidative stress salivary markers and feature of salivary DNA to the patients with chronic periodontitis and free control groups	Salivary thiobarbiturics acid reacting substances were higher in periodontitis subjects than controls and no differences found regarding salivary DNA
Sexton et al²⁸	Assessed the salivary biomarkers (IL-1ß,IL-8,MIP1α, MMP8, OPG,TNF-α) of periodontitis patients	Salivary biomarker level of IL-1ß, MMP8, OPG and MIP1α reflected the disease severity
Tabari et al²⁹	Evaluated the salivary concentration of visfatin level in patients with chronic periodontitis	Increased concentration of salivary visfatin level were significantly higher in periodontitis group
Arroyave et al³⁰	Determined the difference in salivary concentration of sRANKL, osteoprotegrin and its ratio in periodontal disease	Higher salivary concentration of sRANKL, osteoprotegrin and its ration in periodontitis patients
Yesica et al³¹	Investigated the salivary levels of 8-hydroxy-2-deoxy guanosine and human neutrophil elastase complex as salivary biomarker in patient with chronic periodontitis	Increased salivary levels 8-hydroxy-2-deoxy guanosine and human neutrophil elastase in chronic periodontitis patient

5. Forthcoming Biomarker in Saliva for Periodontitis

5.1 Salivary Proteome

A varying group of proteins manifested by a genome or a cell or a tissue or an organism referred as proteome. Mass spectrometry and shot gun proteomics are techniques that are used to identify proteomes².

5.2 Salivary Transcriptome

Transcriptome refers to an RNA molecules present in a single cell or a group of cells. Li et al., demonstrated the elevated RNA molecules in saliva of patients with oral cancer tissues¹⁵.

Zudakov et al., demonstrated the five salivary RNA markers (SPRR1A SPRR3, KRT6A, KRT13, KRT4) lasted till 180days in the saliva and blood samples¹⁶.

6. Conclusion

Thus biomarkers which are present in the saliva act as effective diagnostic tool because of its ease of collection, cost and chair side diagnostic tool. But still a lot more research efforts are necessary to determine the sensitivity and specificity of salivary biomarker and to increase the availability of routine detection methods³².

References

Javaid MA, Ahmed AS, Durand R, Tran SD. Saliva as a diagnostic tool for oral and systemic disease. J Oral Biol Craniofac Res. 2016;6(1):66-75.
[CrossRef] [PubMed] [Google Scholar]
Giannobile WV, Beikler T, Kinney JS, Rameseier CA, Morelli T, Wong DT. Saliva as a diagnostic tool for periodontal disease: Current state and future directions. Periodontology. 2000-2009;50(1):52-64.
[CrossRef] [PubMed] [Google Scholar]
Rocha FRG, de Molon RS, Tonotto MR, Munoz SCSPEM, Sampaio JEC. Use of salivary biomarker for diagnosis of periodontal disease activity: A literature review. World Journal of Dentistry. 2013;4(4):250-5.
[CrossRef] [Google Scholar]
Kaczor-Urbanowicz KE, Carreras-Presas CMCM, Aro K, Tu M, Garcia-Godoy F, Wong DTW. Saliva diagnostics-current views and directions. Exp Biol Med (Maywood). 2017;242(5):459-72.
[CrossRef] [PubMed] [Google Scholar]
Vijayalakshmi BM, Basavaraddi SM, Burde K, Horatti P. Saliva-A diagnostic tool. IOSR Journal of Dental and Medical Sciences. 2013;11(6):96-9.
[Google Scholar]
Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463-6.
[CrossRef] [PubMed] [Google Scholar]
Patil PB, Patil B. Saliva: A diagnostic biomarker of periodontal disease. J Indian Soc Periodontol. 2011;15(4):310-7.
[CrossRef] [PubMed] [Google Scholar]
Teng YT, Sodek J, Mc Cullouch CA. Gingival crevicular fluid gelatinase and its relationship to periodontaldisease in human subjects. J Periodontal Res. 1992;27(5):544-52.
[CrossRef] [PubMed] [Google Scholar]
Sewon L, Karjalainen SM, Sainio M, Seppa O. Calcium and other salivary factors in periodontitis affected subjects prior to treatment. J Clin Periodontol. 1995;22(4):267-70.
[CrossRef] [PubMed] [Google Scholar]
Morgan PR, Shirlaw PJ, Johnson NM, Leigh IM, Lane EB. Potential applications of anti-keratin antibodies in oral diagnosis. J Oral Pathol. 1987;16(4):212-22.
[CrossRef] [PubMed] [Google Scholar]
Raeste AM, Aura A. Rate of migration of oral leukocytesin-patients with periodontitis. Scand J Dent Res. 1978;86(1):43-51.
[PubMed] [Google Scholar]
Klinkhammer JM. Quantitative evaluation of gingivitis and periodontal disease (I): The orogranulocyte migratory rate Periodontics. . 1968;6(5):207-11.
[Google Scholar]
Asikainen S, Alaluusua S, Saxen L. Recovery of A actinomycetemcomitans from teeth, tongue and saliva. J Periodontal. 1991;62(3):203-6.
[CrossRef] [PubMed] [Google Scholar]
De Jong MH, van der Hoeven JS, van Os JH, Olijve JH. Growth of oral streptococcus species and actinomycesvicosus in human saliva. App Environ Microbiol. 1984;47(5):901-4.
[PubMed] [Google Scholar]
Li Y, St John MA, Zhou X, Kim Y, Sinha U, Jordan RC, et al. Salivary transcriptome diagnostics for oral cancer detection. Clin Cancer Res. 2004;10(24):8442-50.
[CrossRef] [PubMed] [Google Scholar]
Zubakov D, Hanekamp E, Kokshoorn M, van Ijcken W, Kayer M. Stable RNA markers for identification of blood and saliva stains revealed from whole genome expression analysis of time-wise degraded samples. Int J Legal Med. 2008;122(2):135-42.
[CrossRef] [PubMed] [Google Scholar]
Baltacioglu E, Yuva P, Aydm G, Alver A, Kahraman C, Karabulut E, Aklam FA. Lipid peroxidation levels and total oxidant/antioxidant status in serum and saliva from patients with chronic and aggressive periodontitis. Oxidative stress index: A new biomarker for periodontal disease? J Periodontol. 2014;85(10):1432-41.
[CrossRef] [PubMed] [Google Scholar]
Costa PP, Trevisan GL, Macedo GO, Palioto DB, Souza SLS, Grisi MFM, Novaes AB Jr, Taba M Jr. Salivary interleukin-6, matrix metalloproteinase-8 and osteoprotegerin in patients with periodontitis and diabetes. J Periodontol. 2010;81(3):384-91.
[CrossRef] [PubMed] [Google Scholar]
Kaur S, Narayanswamy S, Ramesh AV. Comparative evaluation of salivary soluble CD44 levels in periodontal health and disease. Journal of Indian Society of Periodontology. 2014;18(6):734.
[Google Scholar]
Gursoy UK, Kononen E, Pradhan-Palikhe P, Tervahartiala T, Pussinen PJ, Suominen-taipale L, Sora T. Salivary MMP-8, TMP-1, and ICTP as markers of advanced periodontitis. J Clin Periodontal. 2010;37(6):487-93.
[CrossRef] [PubMed] [Google Scholar]
Al-Rawi N, Al-Marzooq F. The relation between periodontopathogenic bacterial levels and resistin in the saliva of obese type 2 diabetic patients. Journal of Diabetes Research 2017
[CrossRef] [PubMed] [Google Scholar]
Nomura Y, Shimada Y, Hanadaa N, Numabec Y, Kamoic K, Sato T, Gomie K, Arai T, Inagaki K, Fukuda M, Noguchi T, Yoshie H. Salivary biomarkers for predicting the progression of chronic periodontitis. Archives of Oral Biology. 2012;57(4):413-20.
[CrossRef] [PubMed] [Google Scholar]
Bertl K, Schoiber A, Haririan H, Laky M, Steiner I, Rausch WD. Non-surgical periodontal therapy influences salivary melatonin levels. Clinical Oral Investigations. 2013;17(4):1219-25.
[CrossRef] [PubMed] [Google Scholar]
Novakovic N, Todorovic T, Rakic M, Milinkovic I, Dozic I, Jankovic S, Aleksic Z, Cakic S. Salivary antioxidants as periodontal biomarkers in evaluation of tissue status and treatment outcome. J Periodont Res. 2014;49(1):129-36.
[CrossRef] [PubMed] [Google Scholar]
Ramseier CA, Kinney JS, Herr AE, Braun T, Sugai JV, Shelburne CA, Rayburn LA, Tran HM, Singh AK, Giannobile WV. Identification of pathogen and host-response markers correlated with periodontal disease. J Periodontol. 2009;80(3):436-46.
[CrossRef] [PubMed] [Google Scholar]
Miller CS, King CP Jr, Langub C, Kryscio RJ, Thomas MV. Salivary biomarkers of existing periodontal disease: A cross-sectional study. J Am Dent Assoc. 2006;137(3):322-9.
[CrossRef] [PubMed] [Google Scholar]
Baňasová L, Kamodyová N, Janšáková K, Tóthova L, Stanko P, Turňa J, Celec P. Salivary DNA and markers of oxidative stress in patients with chronic periodontitis. Clinical Oral Investigations. 2015;19(2):201-7.
[CrossRef] [PubMed] [Google Scholar]
Sexton WM, Lin Y, Kryscio RJ, Dawson III DR, Ebersole JL, Miller CS. Salivary biomarkers of periodontal disease in response to treatment. J Clin Periodontol. 2011;38(5):434-41.
[CrossRef] [Google Scholar]
Tabari ZA, Azadmehr A, Nohekhan A, Naddafpour N, Ghaedi FB. Salivary visfatin concentrations in patients with chronic periodontitis. J Periodontol. 2014;85(8):1081-5.
[CrossRef] [PubMed] [Google Scholar]
Tobon-Arroyave SI, Isaza-Guzman DM, Restrepo-Cadavid EM, Zapata-Molina SM, Martınez-Pabon MC. Association of salivary levels of the bone remodelling regulators sRANKL and OPG with periodontal clinical status. J Clin Periodontol. 2012;39(12):1132-40.
[CrossRef] [Google Scholar]
Villa-Correa YA, Isaza-Guzmán DM, Tobón-Arroyave SI. Prognostic Value of 8-Hydroxy-2'-Deoxyguanosine and Human Neutrophil Elastase/α1-Proteinase Inhibitor Complex as Salivary Biomarkers of Oxidative Stress in Chronic Periodontitis. Journal of periodontology. 2015;86(11):1260-7.
[CrossRef] [Google Scholar]
Podzimek S, Vondrackova L, Duskova J, Janatova T, Broukal Z. Salivary markers for periodontal and general disease. Disease Markers 2016
[CrossRef] [PubMed] [Google Scholar]

Show Sections

[1] Javaid MA, Ahmed AS, Durand R, Tran SD. Saliva as a diagnostic tool for oral and systemic disease. J Oral Biol Craniofac Res. 2016;6(1):66-75.
[CrossRef] [PubMed] [Google Scholar]

[2] Giannobile WV, Beikler T, Kinney JS, Rameseier CA, Morelli T, Wong DT. Saliva as a diagnostic tool for periodontal disease: Current state and future directions. Periodontology. 2000-2009;50(1):52-64.
[CrossRef] [PubMed] [Google Scholar]

[3] Rocha FRG, de Molon RS, Tonotto MR, Munoz SCSPEM, Sampaio JEC. Use of salivary biomarker for diagnosis of periodontal disease activity: A literature review. World Journal of Dentistry. 2013;4(4):250-5.
[CrossRef] [Google Scholar]

[4] Kaczor-Urbanowicz KE, Carreras-Presas CMCM, Aro K, Tu M, Garcia-Godoy F, Wong DTW. Saliva diagnostics-current views and directions. Exp Biol Med (Maywood). 2017;242(5):459-72.
[CrossRef] [PubMed] [Google Scholar]

[5] Vijayalakshmi BM, Basavaraddi SM, Burde K, Horatti P. Saliva-A diagnostic tool. IOSR Journal of Dental and Medical Sciences. 2013;11(6):96-9.
[Google Scholar]

[6] Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463-6.
[CrossRef] [PubMed] [Google Scholar]

[7] Patil PB, Patil B. Saliva: A diagnostic biomarker of periodontal disease. J Indian Soc Periodontol. 2011;15(4):310-7.
[CrossRef] [PubMed] [Google Scholar]

[8] Teng YT, Sodek J, Mc Cullouch CA. Gingival crevicular fluid gelatinase and its relationship to periodontaldisease in human subjects. J Periodontal Res. 1992;27(5):544-52.
[CrossRef] [PubMed] [Google Scholar]

[9] Sewon L, Karjalainen SM, Sainio M, Seppa O. Calcium and other salivary factors in periodontitis affected subjects prior to treatment. J Clin Periodontol. 1995;22(4):267-70.
[CrossRef] [PubMed] [Google Scholar]

[10] Morgan PR, Shirlaw PJ, Johnson NM, Leigh IM, Lane EB. Potential applications of anti-keratin antibodies in oral diagnosis. J Oral Pathol. 1987;16(4):212-22.
[CrossRef] [PubMed] [Google Scholar]

[11] Raeste AM, Aura A. Rate of migration of oral leukocytesin-patients with periodontitis. Scand J Dent Res. 1978;86(1):43-51.
[PubMed] [Google Scholar]

[12] Klinkhammer JM. Quantitative evaluation of gingivitis and periodontal disease (I): The orogranulocyte migratory rate Periodontics. . 1968;6(5):207-11.
[Google Scholar]

[13] Asikainen S, Alaluusua S, Saxen L. Recovery of A actinomycetemcomitans from teeth, tongue and saliva. J Periodontal. 1991;62(3):203-6.
[CrossRef] [PubMed] [Google Scholar]

[14] De Jong MH, van der Hoeven JS, van Os JH, Olijve JH. Growth of oral streptococcus species and actinomycesvicosus in human saliva. App Environ Microbiol. 1984;47(5):901-4.
[PubMed] [Google Scholar]

[15] Li Y, St John MA, Zhou X, Kim Y, Sinha U, Jordan RC, et al. Salivary transcriptome diagnostics for oral cancer detection. Clin Cancer Res. 2004;10(24):8442-50.
[CrossRef] [PubMed] [Google Scholar]

[16] Zubakov D, Hanekamp E, Kokshoorn M, van Ijcken W, Kayer M. Stable RNA markers for identification of blood and saliva stains revealed from whole genome expression analysis of time-wise degraded samples. Int J Legal Med. 2008;122(2):135-42.
[CrossRef] [PubMed] [Google Scholar]

[17] Baltacioglu E, Yuva P, Aydm G, Alver A, Kahraman C, Karabulut E, Aklam FA. Lipid peroxidation levels and total oxidant/antioxidant status in serum and saliva from patients with chronic and aggressive periodontitis. Oxidative stress index: A new biomarker for periodontal disease? J Periodontol. 2014;85(10):1432-41.
[CrossRef] [PubMed] [Google Scholar]

[18] Costa PP, Trevisan GL, Macedo GO, Palioto DB, Souza SLS, Grisi MFM, Novaes AB Jr, Taba M Jr. Salivary interleukin-6, matrix metalloproteinase-8 and osteoprotegerin in patients with periodontitis and diabetes. J Periodontol. 2010;81(3):384-91.
[CrossRef] [PubMed] [Google Scholar]

[19] Kaur S, Narayanswamy S, Ramesh AV. Comparative evaluation of salivary soluble CD44 levels in periodontal health and disease. Journal of Indian Society of Periodontology. 2014;18(6):734.
[Google Scholar]

[20] Gursoy UK, Kononen E, Pradhan-Palikhe P, Tervahartiala T, Pussinen PJ, Suominen-taipale L, Sora T. Salivary MMP-8, TMP-1, and ICTP as markers of advanced periodontitis. J Clin Periodontal. 2010;37(6):487-93.
[CrossRef] [PubMed] [Google Scholar]

[21] Al-Rawi N, Al-Marzooq F. The relation between periodontopathogenic bacterial levels and resistin in the saliva of obese type 2 diabetic patients. Journal of Diabetes Research 2017
[CrossRef] [PubMed] [Google Scholar]

[22] Nomura Y, Shimada Y, Hanadaa N, Numabec Y, Kamoic K, Sato T, Gomie K, Arai T, Inagaki K, Fukuda M, Noguchi T, Yoshie H. Salivary biomarkers for predicting the progression of chronic periodontitis. Archives of Oral Biology. 2012;57(4):413-20.
[CrossRef] [PubMed] [Google Scholar]

[23] Bertl K, Schoiber A, Haririan H, Laky M, Steiner I, Rausch WD. Non-surgical periodontal therapy influences salivary melatonin levels. Clinical Oral Investigations. 2013;17(4):1219-25.
[CrossRef] [PubMed] [Google Scholar]

[24] Novakovic N, Todorovic T, Rakic M, Milinkovic I, Dozic I, Jankovic S, Aleksic Z, Cakic S. Salivary antioxidants as periodontal biomarkers in evaluation of tissue status and treatment outcome. J Periodont Res. 2014;49(1):129-36.
[CrossRef] [PubMed] [Google Scholar]

[25] Ramseier CA, Kinney JS, Herr AE, Braun T, Sugai JV, Shelburne CA, Rayburn LA, Tran HM, Singh AK, Giannobile WV. Identification of pathogen and host-response markers correlated with periodontal disease. J Periodontol. 2009;80(3):436-46.
[CrossRef] [PubMed] [Google Scholar]

[26] Miller CS, King CP Jr, Langub C, Kryscio RJ, Thomas MV. Salivary biomarkers of existing periodontal disease: A cross-sectional study. J Am Dent Assoc. 2006;137(3):322-9.
[CrossRef] [PubMed] [Google Scholar]

[27] Baňasová L, Kamodyová N, Janšáková K, Tóthova L, Stanko P, Turňa J, Celec P. Salivary DNA and markers of oxidative stress in patients with chronic periodontitis. Clinical Oral Investigations. 2015;19(2):201-7.
[CrossRef] [PubMed] [Google Scholar]

[28] Sexton WM, Lin Y, Kryscio RJ, Dawson III DR, Ebersole JL, Miller CS. Salivary biomarkers of periodontal disease in response to treatment. J Clin Periodontol. 2011;38(5):434-41.
[CrossRef] [Google Scholar]

[29] Tabari ZA, Azadmehr A, Nohekhan A, Naddafpour N, Ghaedi FB. Salivary visfatin concentrations in patients with chronic periodontitis. J Periodontol. 2014;85(8):1081-5.
[CrossRef] [PubMed] [Google Scholar]

[30] Tobon-Arroyave SI, Isaza-Guzman DM, Restrepo-Cadavid EM, Zapata-Molina SM, Martınez-Pabon MC. Association of salivary levels of the bone remodelling regulators sRANKL and OPG with periodontal clinical status. J Clin Periodontol. 2012;39(12):1132-40.
[CrossRef] [Google Scholar]

[31] Villa-Correa YA, Isaza-Guzmán DM, Tobón-Arroyave SI. Prognostic Value of 8-Hydroxy-2'-Deoxyguanosine and Human Neutrophil Elastase/α1-Proteinase Inhibitor Complex as Salivary Biomarkers of Oxidative Stress in Chronic Periodontitis. Journal of periodontology. 2015;86(11):1260-7.
[CrossRef] [Google Scholar]

[32] Podzimek S, Vondrackova L, Duskova J, Janatova T, Broukal Z. Salivary markers for periodontal and general disease. Disease Markers 2016
[CrossRef] [PubMed] [Google Scholar]

Saliva- A Tool for Diagnosis in Periodontal Disease

Abstract

Keywords

Periodontitis

Salivary Biomarkers

Salivary Enzymes

1. Introduction

2. Emerging Diagnostic Tool-Saliva

3. Gratification of Saliva over Gingival Crevicular Fluid5

4. Salivary Biomarkers in Periodontal Diseases

4.1 Markers Affecting Dental Biofilm

4.1.1 Specific Marker

4.1.2 Non Specific Biomarker (Table 1)

4.2 Systemic Biomarker - C-Reactive Protein

4.3 Markers Present in Inflamed Periodontium

4.4 Markers Expressed in Alveolar Bone Loss

4.5 Salivary Enzymes and Ions

4.6 Growth Factor as a Salivary Biomarker

4.7 Epithelial Keratins

4.8 Hormones

4.9 Inflammatory Cells and Bacteria

4.10 Volatiles and Oxidative Stress Marker

5. Forthcoming Biomarker in Saliva for Periodontitis

5.1 Salivary Proteome

5.2 Salivary Transcriptome

6. Conclusion

References

Suggested read for related articles:

3. Gratification of Saliva over Gingival Crevicular Fluid⁵