Salivary diagnostics for periodontal

diseases
William V. Giannobile, DDS, DMSc

eriodontal diseases are chronic infectious diseases driven by microbial biofilms that populate
tooth root surfaces.1 Periodontitis is a leading
cause of tooth loss in adults, affecting more than
50 percent of the U.S. population.2 Chronic periodontal
infections activate the patients host response to liberate a myriad of metabolic byproducts at the interface
between the tooth and the periodontal pocket. This
process leads to the release of destructive cellular
enzymes, cytokines, chemokines and other mediators of
tissue destruction. Periodontitis is implicated in a
variety of polygenic diseases, such as rheumatoid
arthritis,3 cardiovascular disease4,5 and stroke.6 The
bacterial biofilm serves as a long-term delivery system
for oral microorganisms that adhere to teeth, leading to
a repeated microbial challenge and downstream effects
on the hosts local and systemic immunity.6,7
The authors of a recent systematic review suggested
that host-derived diagnostics are at an early stage of
development.8 Several challenges remain regarding the
use of saliva as a medium for determining periodontal
disease, including factors such as diurnal variation,
drug influences and salivary flow rates.9,10 Despite
some of these challenges and limitations, opportunities
in clinical periodontics exist with regard to the identification, monitoring and tracking of disease progression
in patients through salivary diagnostics (Figure 1).11,12
Periodontal disease progression involves infection,
inflammation and subsequent alveolar bone loss. Biological phenotypes may be of value because they capture the microbial and inflammatory burden affecting
periodontitis progression at the individual patient
level. These phenotypes are important for the development of disease classifications, for the rational design
of targeted therapeutic drugs, and for oral diagnostics
for periodontal disease classification and subsequent
treatment.13,14 Furthermore, periodontal disease
activity is not well defined because clinicians often use

6S JADA 143(10 suppl)

http://jada.ada.org

AB STRACT
Background and Overview. The use
of salivary diagnostics continues to develop
and advance the field of risk determination
for periodontal diseases. Researchers are
investigating genetic, microbial and protein
biomarkers with the objective of translating
findings to such aspects of clinical care as
broad patient screening, monitoring and
treatment planning.
Methods. In this review, the author
briefly explores currently available salivary
diagnostics used to identify bacteria prevalent in periodontal disease, and focuses on
the future development and use of a variety
of rapid disease detection platforms, such as
lab-on-a-chip, as a point-of-care device for
identification of patients risk.
Conclusions and Clinical Implications. Several diagnostic tests are commercially available, and point-of-care tests are
under development. However, challenges
remain regarding the introduction of these
technologies to clinical practice and adoption by dental practitioners for promotion of
personalized oral health care.
Key Words. Salivary diagnostics; personalized medicine; personalized health care;
pharmacogenomics; periodontitis; lab-on-achip; biofilms.
JADA 2012;143(10 suppl):6S-11S.
Dr. Giannobile is the Najjar Endowed Professor and the chair,
Department of Periodontics and Oral Medicine, and the director,
Michigan Center for Oral Health Research, School of Dentistry,
University of Michigan, 1011 N. University Ave., Ann Arbor, Mich.
48109-1078, e-mail william.giannobile@umich.edu. Address
reprint requests to Dr. Giannobile.

October 2012

Copyright 2012 American Dental Association. All rights reserved.

Inherited/Acquired
Genetic Factors

Biological Onset
of Disease

Disease Detection
by Screening Test

Anatomical Loss
of Tooth Support

Genetic Tests

Microbial Tests

Salivary Protein
Biomarkers

Clinical Examination or
Intraoral Imaging

Detectable Subclinical Phase

Figure 1. Timeline of periodontal disease progression. Researchers and clinicians can identify inherited or acquired risk factors by using
genetic tests for periodontal disease susceptibility. The biological onset of periodontal diseases is initiated by pathogens that can be
identified by means of microbial tests (cultures or genes). Screening tests for disease detection can involve the use of salivary protein
biomarkers. The clinical diagnosis of disease includes indicators such as pocket depth or radiographic evidence of bone loss.

error-prone measures, including pocket depth,

clinical attachment level and bone level, making
determinations of clinical progression difficult.15
Given the localized nature and proximity of
periodontal lesions within the oral cavity, saliva
is a natural biological fluid for measurement of
microbial and protein biomarkers of the disease
process.12 Recent data pertaining to the use of
genetic, microbial16 and protein saliva-based
byproducts support the predictive value to forecast gingival inflammation17 or periodontal bone
destruction in the clinical setting.18,19
Researchers have demonstrated salivas ease
of use in point-of-care (POC) applications for
multiple diseases.20 However, with regard to
periodontal disease, a large body of research has
focused on gingival crevicular fluid (GCF) biomarkers that reveal local disease status but represent an approach that is technically difficult
(that is, difficulty in accessing all tooth sites,
salivary contamination or bleeding from the
sites) to implement clinically.21,22 Saliva is more
readily available and easier to collect than is
GCF.
Substantial clinical information is available
pertaining to the use of matrix metalloproteinase8 (MMP-8), an enzyme responsible for tissue
destruction, as a diagnostic tool.20,23-26 An MMP-8
oral test became available commercially in
2010. This test has shown reasonable sensitivity
and specificity in diagnosing active or stable
periodontal lesions in patients who smoke, as
well as in those who do not smoke.27 New
methodological approaches allow researchers to
evaluate multiple salivary biomarkers
including MMP-8,28-31 microbial factors,32
viruses33 and proinflammatory cytokines such as
interleukin (IL) 131,34-36 or IL-1737from a single

saliva sample to predict disease. Although these

tests are becoming more readily available, their
adoption by oral health care providers remains
slow owing, in part, to the lack of treatment
algorithms that outline clearly their use in clinical care delivery.
Researchers have evaluated salivary biomarkers of disease in patients with periodontitis comorbidities, including rheumatoid
arthritis38 and diabetes.39 In addition, researchers have used biomarkers in local oral
wound fluids to predict patients responses to
therapies such as periodontal surgery combined
with MMP inhibition40 or to oral tissue engineering constructs.40-42 Investigators also have
used these wound repair biomarkers to determine the tissue-healing response of patients
undergoing intraoral soft-tissue transplant
procedures.43
MICROBIAL AND HOST--RESPONSE
BIOMARKERS OF PERIODONTITIS

The use of periodontal signatures for disease

classification based on the patients phenotype
is beneficial in the development of diagnostic
tests.13 Specific biofilm organisms or exposures
may have the capacity to affect the inflammatory set point of local tissues in certain patients
via epigenetic changes as a result of hypermethylation of the DNA within nuclei of affected
soft tissues across time in a chronic disease such
as periodontitis.44,45 Therefore, the use of rapid
POC diagnostics that identify disease in the
context of the host-microbe interaction likely
ABBREVIATION KEY. GCF: Gingival crevicular fluid.
IL: Interleukin. MMP-8: Matrix metalloproteinase-8.
POC: Point of care.
JADA 143(10 suppl)

http://jada.ada.org

Copyright 2012 American Dental Association. All rights reserved.

October 2012 7S

will lead to more rationally tailored therapeutic

strategies. The biofilm-gingival interface provides a molecular epidemiologic viewpoint that
patients clinical phenotypes translate directly
to biological phenotypes on the basis of antibody
response, microbial biofilm levels and local
proinflammatory cytokines.14
When investigators consider MMP-8 or
MMP-9 with the red complex, highly virulent
periodontal pathogens Treponema denticola, Porphyromonas gingivalis or Tannerella forsythia,
they are better able to predict periodontal
status.46 The red complex bacteria are known
for their potent ability to produce the trypsinlike
enzyme activity that is responsible for destroying collagen matrices.47 Thus, data that
combine microbial and host-derived factors substantiate the use of MMP-destroying enzymes
and corresponding initiating pathogens such as
T. denticola to identify periodontal disease. The
greatest utility of these diagnostic approaches is
the development of predictive models for disease,
which require validation in large, longitudinal
studies (see ClinicalTrials.gov NCT01489839).
The results of recent longitudinal studies in
which investigators examined predictive biomarkers of progressive periodontitis (microbial
biomarkers, host-response biomarkers or both)
illustrate mediator signatures for patients with
active periodontal disease.48-50
To date, there is no single biomarker that is
specific for periodontal disease. Therefore, there
is strong potential for the use of microbial (initiator) and host-response (responder) biomarkers
in combination to enhance identification of the
disease process, given the multifactorial nature
of periodontal diseases.48 Future in-office applications of rapid POC diagnostics that could enable
clinicians to measure proteins, genes or biofilm
pathogens in saliva may lead to enhanced disease identification and improved oral health.11,51
Molecular approaches, such as evaluation of the
transcriptomes from gingival and periodontal tissues, offer the potential for future applications,
although not currently in a salivary platform.52,53
The transcriptome is the set of RNA transcripts
that differs from the genome (that is, set at
birth); the transcriptome can be influenced by
environmental challenges, such as microbial
infection. Moreover, the metabolic products from
the microbiota have potential as risk indicators,
as identified in a recent metabolomic study by
Barnes and colleagues.54
Researchers have identified pathogens such
as P. gingivalis, T. forsythia and Prevotella
intermedia, as well as viruses such as EpsteinBarr virus, in saliva from patients with progres8S JADA 143(10 suppl)

http://jada.ada.org

sive periodontitis.16 Early-stage, point-ofdetection approaches offer the ability to target

antibodies associated with infectious diseases
such as human immunodeficiency virus and
H1N1 influenza virus.55,56 Although viruses are
not strongly implicated in periodontal diseases,
the use of multianalyte techniques that consider
both viral and microbial infectious agents in
saliva may be beneficial.57
ORAL-BASED GENETIC AND GENOMIC
APPROACHES TO IDENTIFYING
PERIODONTAL DISEASE RISK

Genetic and genomic information has increased

greatly since completion of the Human Genome
Project nearly 10 years ago, with considerable
implications for oral health care.58 Findings
from studies in the areas of genetics (that is,
focusing on the effects of single genes in isolation) and genomics (that is, the study of interactions between all of a patients genes and environmental factors) are advancing personalized
dental medicine.59 Therefore, genetic and genomic approaches have considerable clinical and
patient utility 60 as they relate to disease identification for a polygenic disorder such as chronic
periodontitis.61
Researchers have estimated that variations
in more than 70 genes are associated with periodontitis.62 This has important implications
regarding the use of genetic tests administered
via oral-based diagnostic platforms to determine
a patients risk of developing periodontal diseases. A patients DNA can be captured with a
saliva-saline matrix oral rinse sample
(MyPerioID PST, OralDNA Labs, Brentwood,
Tenn.), which is sent to a central laboratory for
rapid analysis of genotypic status for IL-1. This
test is based on the premise that a single
nucleotide polymorphism of the IL-1 gene is a
susceptibility factor for periodontal disease.63
IL-1 polymorphisms connote risk of tooth loss64
and advancing periodontal diseases.65 They are
complemented by laboratory tests of microbial
plaque biofilm (MyPerioPath, OralDNA Labs).66
With readily accessible and robust salivary diagnostics for the identification of DNA, genomewide association studies offer significant potential for the discovery of gene expression indicating susceptibility to periodontal disease modulated by microbial infection.67
Genomic technologies are rapidly advancing
our ability to exploit saliva-based diagnostics for
application to personalized oral health care.
Investigators use bioinformatics widely via highthroughput data generation in next-generation
sequencing and microarray techniques.59 These

October 2012

Copyright 2012 American Dental Association. All rights reserved.

Figure 2. Application of salivary diagnostics to the periodontal practice of the future. A point-of-care diagnostic may be available in
which a patient provides an oral sample that is delivered to the chairside or to a laboratory device. The result is interpreted by the oral
health care provider, who then educates the patient about the findings from the biomarker report. The diagnostic test may reveal a
patients susceptibility to disease (for example, a genetic test) or provide a real-time assessment of the patients disease status via the
use of microbiological or protein markers of periodontal infection, destruction or both.

technologies are available in platforms that can

be used for more rapid genetic analyses to detect
periodontal disease.68 Therefore, genomic, proteomic and transcriptomic networks relating
directly to the maintenance of oral health can
serve as multipronged approaches to personalized oral health care in periodontology.
DEVELOPMENT OF CHAIRSIDE
PERIODONTAL DISEASE DIAGNOSTICS

The development of chairside POC devices for

oral health surveillance likely will require minimal clinical training and resources; may lead to
better use by properly trained practitioners (and
patients) for simpler and less intensive treatment; and likely will result in more costeffective oral health care delivery.69 In the
future, dental practitioners may be able to
screen patients for periodontal disease in nondental settings, such as community health care
facilities, or through at-home use of over-thecounter devices, allowing these devices to be
directed toward more personalized treatments.11
Patients will benefit by being much more
involved in their own health behaviors that
could increase their overall compliance with recommended treatment regimens. Underserved
communities and resource-limited areas may
benefit from improved access to oral health
assessment programs in comparison with the
current, poorly used screening programs.70 The
ability to identify and monitor patient populations that have rare diseases will help foster
better identification of at-risk people and
increase access to treatment for those most in
need. This, in turn, will improve the periodontal
health of the public in a much broader sense
(Figure 2).

CONCLUSIONS

The future of saliva-based techniques for diagnosing periodontitis is promising; however, as

with any new technology, process issues need to
be addressed before they are used widely in clinical settings.11 Validation of periodontal diagnostics will need to be benchmarked with existing
standard measures of disease, including alveolar bone height and clinical attachment
levels.21 One of the greatest challenges is not in
going from bench to chairside, but in going from
chairside to clinical practice. Acceptance by oral
health care providers and third-party payers is
necessary and may prove difficult to achieve.71
The dental community generally is not familiar
with mass screening of populations for oral and
systemic diseases.72 Should more effective periodontal therapy be delivered by using treatment
algorithms, clinicians will be more likely to
adopt new diagnostic approaches to clinical
decision making. Also, clear outcomes are
lacking with regard to how the currently available approaches improve clinical care delivery.
We must place a greater emphasis on educating clinicians in diagnostics, disease risk and
disease prevention through the public health
sector before they will integrate salivary diagnostics into routine dental practice.73 Although much
needs to be done, saliva-based diagnostics offer a
promising future for diagnosing periodontal diseases and monitoring treatment outcomes.
Disclosure. Dr. Giannobile holds intellectual property related to
the salivary diagnostics field.
This work was supported by grants UL1RR024986 and U01-DE021127 from the National Institutes of Health, Bethesda, Md.
1. Darveau RP. Periodontitis: a polymicrobial disruption of host
homeostasis. Nat Rev Microbiol 2010;8(7):481-490.

JADA 143(10 suppl)

http://jada.ada.org

Copyright 2012 American Dental Association. All rights reserved.

October 2012 9S

2. Eke PI, Thornton-Evans GO, Wei L, Borgnakke WS, Dye BA.

Accuracy of NHANES periodontal examination protocols (published
online ahead of print Sept. 21, 2010). J Dent Res 2010;89(11):
1208-1213. doi:10.1177/0022034510377793.
3. Rutger Persson G. Rheumatoid arthritis and periodontitis:
inflammatory and infectious connectionsreview of the literature
(published online ahead of print Feb. 13, 2012). J Oral Microbiol
2012;4. doi:10.3402/jom.v4i0.11829.
4. Beck JD, Offenbacher S, Williams R, Gibbs P, Garcia R. Periodontitis: a risk factor for coronary heart disease? Ann Periodontol
1998;3(1):127-141.
5. Jin LJ, Armitage GC, Klinge B, Lang NP, Tonetti M, Williams
RC. Global oral health inequalities: task groupperiodontal disease.
Adv Dent Res 2011;23(2):221-226.
6. Kebschull M, Demmer RT, Papapanou PN. Gum bug, leave my
heart alone!: epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis (published online ahead of print
July 16, 2010). J Dent Res 2010;89(9):879-902. doi:10.1177/
0022034510375281.
7. Garlet GP. Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction
viewpoints (published online ahead of print Aug. 25, 2010). J Dent
Res 2010;89(12):1349-1363. doi:10.1177/0022034510376402.
8. Buduneli N, Kinane DF. Host-derived diagnostic markers related
to soft tissue destruction and bone degradation in periodontitis (published online ahead of print Feb. 16, 2011). J Clin Periodontol
2011;38(suppl 11):85-105. doi:10.1111/j.1600-051X.2010.01670.x.
9. Baum BJ, Yates JR 3rd, Srivastava S, Wong DT, Melvin JE. Scientific frontiers: emerging technologies for salivary diagnostics. Adv
Dent Res 2011;23(4):360-368.
10. Liu J, Duan Y. Saliva: a potential media for disease diagnostics
and monitoring (published online ahead of print Feb. 18, 2012). Oral
Oncol 2012;48(7):569-577. doi:10.1016/j.oraloncology.2012.01.021.
11. Giannobile WV, McDevitt JT, Niedbala RS, Malamud D. Translational and clinical applications of salivary diagnostics. Adv Dent
Res 2011;23(4):375-380.
12. Miller CS, Foley JD, Bailey AL, et al. Current developments in
salivary diagnostics. Biomark Med 2010;4(1):171-189.
13. Casanova JL, Abel L. The human model: a genetic dissection of
immunity to infection in natural conditions. Nat Rev Immunol 2004;
4(1):55-66.
14. Offenbacher S, Barros SP, Singer RE, Moss K, Williams RC,
Beck JD. Periodontal disease at the biofilm-gingival interface.
J Periodontol 2007;78(10):1911-1925.
15. Giannobile WV. Clinical attachment level change as an outcome
measure for therapies that slow the progression of periodontal disease (commentary). Int J Acad Periodontol 2005;7(4 suppl):172-174.
16. Saygun I, Nizam N, Keskiner I, et al. Salivary infectious agents
and periodontal disease status (published online ahead of print Jan.
25, 2011). J Periodontal Res 2011;46(2):235-239. doi:10.1111/j.16000765.2010.01335.x.
17. Lee A, Ghaname CB, Braun TM, et al. Bacterial and salivary
biomarkers predict the gingival inflammatory profile (published
online ahead of print May 12, 2011). J Periodontol 2012;83(1):79-89.
doi:10.1902/jop.2011.110060.
18. Al-Sabbagh M, Alladah A, Lin Y, et al. Bone remodelingassociated salivary biomarker MIP-1 distinguishes periodontal disease from health (published online ahead of print Nov. 29, 2011).
J Periodontal Res 2012;47(3):389-395. doi:10.1111/j.16000765.2011.01445.x.
19. Frodge BD, Ebersole JL, Kryscio RJ, Thomas MV, Miller CS.
Bone remodeling biomarkers of periodontal disease in saliva.
J Periodontol 2008;79(10):1913-1919.
20. Christodoulides N, Floriano PN, Miller CS, et al. Lab-on-a-chip
methods for point-of-care measurements of salivary biomarkers of
periodontitis. Ann N Y Acad Sci 2007;1098:411-428.
21. Giannobile WV, Beikler T, Kinney JS, Ramseier CA, Morelli T,
Wong DT. Saliva as a diagnostic tool for periodontal disease: current
state and future directions. Periodontol 2000 2009;50:52-64.
22. Zhang L, Henson BS, Camargo PM, Wong DT. The clinical
value of salivary biomarkers for periodontal disease. Periodontol
2000 2009;51:25-37.
23. Golub LM, Lee HM, Greenwald RA, et al. A matrix metalloproteinase inhibitor reduces bone-type collagen degradation fragments
and specific collagenases in gingival crevicular fluid during adult
periodontitis. Inflamm Res 1997;46(8):310-319.
24. Herr AE, Hatch AV, Throckmorton DJ, et al. Microfluidic
immunoassays as rapid saliva-based clinical diagnostics (published

10S JADA 143(10 suppl)

http://jada.ada.org

online ahead of print March 20, 2007). Proc Natl Acad Sci U S A
2007;104(13):5268-5273. doi:10.1073/pnas.0607254104.
25. Kinane DF, Darby IB, Said S, et al. Changes in gingival crevicular fluid matrix metalloproteinase-8 levels during periodontal treatment and maintenance. J Periodontal Res 2003;38(4):400-404.
26. Prescher N, Maier K, Munjal SK, et al. Rapid quantitative
chairside test for active MMP-8 in gingival crevicular fluid: first clinical data. Ann N Y Acad Sci 2007;1098:493-495.
27. Mntyl P, Stenman M, Kinane D, et al. Monitoring periodontal disease status in smokers and nonsmokers using a gingival
crevicular fluid matrix metalloproteinase-8-specific chair-side test.
J Periodontal Res 2006;41(6):503-512.
28. Costa PP, Trevisan GL, Macedo GO, et al. Salivary interleukin6, matrix metalloproteinase-8, and osteoprotegerin in patients with
periodontitis and diabetes. J Periodontol 2010;81(3):384-391.
29. Heikkinen AM, Sorsa T, Pitkniemi J, et al. Smoking affects
diagnostic salivary periodontal disease biomarker levels in adolescents. J Periodontol 2010;81(9):1299-1307.
30. Gursoy UK, Knnen E, Pradhan-Palikhe P, et al. Salivary
MMP-8, TIMP-1, and ICTP as markers of advanced periodontitis.
J Clin Periodontol 2010;37(6):487-493.
31. Miller CS, King CP Jr, Langub MC, Kryscio RJ, Thomas MV.
Salivary biomarkers of existing periodontal disease: a cross-sectional
study. JADA 2006;137(3):322-329.
32. Iwano Y, Sugano N, Matsumoto K, et al. Salivary microbial
levels in relation to periodontal status and caries development.
J Periodontal Res 2010;45(2):165-169.
33. Dawson DR 3rd, Wang C, Danaher RJ, et al. Salivary levels of
Epstein-Barr virus DNA correlate with subgingival levels, not
severity of periodontitis (published online ahead of print June 12,
2009). Oral Dis 2009;15(8):554-559. doi:10.1111/j.1601-0825.2009.
01595.x.
34. Fine DH, Markowitz K, Furgang D, et al. Macrophage inflammatory protein-1alpha: a salivary biomarker of bone loss in a longitudinal cohort study of children at risk for aggressive periodontal
disease? J Periodontol 2009;80(1):106-113.
35. Ng PY, Donley M, Hausmann E, Hutson AD, Rossomando EF,
Scannapieco FA. Candidate salivary biomarkers associated with
alveolar bone loss: cross-sectional and in vitro studies. FEMS
Immunol Med Microbiol 2007;49(2):252-260.
36. Suh K-I, Kim Y-K, Kho H-S. Salivary levels of IL-1, IL-6, IL-8,
and TNF- in patients with burning mouth syndrome. Arch Oral Biol
2009;54(9):797-802.
37. Ozaka O, Nalbantsoy A, Buduneli N. Interleukin-17 and
interleukin-18 levels in saliva and plasma of patients with chronic
periodontitis (published online ahead of print June 3, 2011). J Periodontal Res 2011;46(5):592-598. doi:10.1111/j.1600-0765.2011.01377.x.
38. Mirrielees J, Crofford LJ, Lin Y, et al. Rheumatoid arthritis and
salivary biomarkers of periodontal disease (published online ahead of
print Sept. 28, 2010). J Clin Periodontol 2010;37(12):1068-1074.
doi:10.1111/j.1600-051X.2010.01625.x.
39. Gms P, Buduneli N, Cetinkalp S, et al. Salivary antioxidants
in patients with type 1 or 2 diabetes and inflammatory periodontal
disease: a case-control study. J Periodontol 2009;80(9):1440-1446.
40. Gapski R, Hasturk H, Van Dyke TE, et al. Systemic MMP inhibition for periodontal wound repair: results of a multi-centre
randomized-controlled clinical trial. J Clin Periodontol 2009;36(2):
149-156.
41. Cooke JW, Sarment DP, Whitesman LA, et al. Effect of
rhPDGF-BB delivery on mediators of periodontal wound repair.
Tissue Eng 2006;12(6):1441-1450.
42. Sarment DP, Cooke JW, Miller SE, et al. Effect of rhPDGF-BB
on bone turnover during periodontal repair. J Clin Periodontol
2006;33(2):135-140.
43. Morelli T, Neiva R, Nevins ML, et al. Angiogenic biomarkers
and healing of living cellular constructs (published online ahead of
print Jan. 19, 2011). J Dent Res 2011;90(4):456-462. doi:10.1177/
0022034510389334.
44. Bobetsis YA, Barros SP, Lin DM, et al. Bacterial infection promotes DNA hypermethylation. J Dent Res 2007;86(2):169-174.
45. Kornman K, Duff G, Reilly P. Re: A critical assessment of
interleukin-1 (IL-1) genotyping when used in a genetic susceptibility
test for severe chronic periodontitis. Greenstein G, Hart TC
(2002;73:231-247) (letter). J Periodontol 2002;73(12):1553-1556;
authors response: 1556-1558.
46. Ramseier CA, Kinney JS, Herr AE, et al. Identification of
pathogen and host-response markers correlated with periodontal disease. J Periodontol 2009;80(3):436-446.

October 2012

Copyright 2012 American Dental Association. All rights reserved.

47. Loesche WJ, Syed SA, Stoll J. Trypsin-like activity in subgingival plaque: a diagnostic marker for spirochetes and periodontal disease? J Periodontol 1987;58(4):266-273.
48. Kinney JS, Morelli T, Braun T, et al. Saliva/pathogen biomarker signatures and periodontal disease progression (published
online ahead of print March 15, 2011) (published correction appears
in J Dent Res 2011;90[8]:1037). J Dent Res 2011;90(6):752-758.
doi:10.1177/0022034511399908.
49. Nomura Y, Shimada Y, Hanada N, et al. Salivary biomarkers
for predicting the progression of chronic periodontitis (published
online ahead of print Oct. 24, 2011). Arch Oral Biol 2012;57(4):
413-420. doi:10.1016/j.archoralbio.2011.09.011.
50. Sexton WM, Lin Y, Kryscio RJ, Dawson DR 3rd, Ebersole JL,
Miller CS. Salivary biomarkers of periodontal disease in response to
treatment (published online ahead of print April 11, 2011). J Clin
Periodontol 2011;38(5):434-441. doi:10.1111/j.1600-051X.2011.01706.x.
51. Giannobile WV, Wong DT. Salivary diagnostics: oral health and
beyond! J Dent Res 2011;90(10):1153-1154.
52. Demmer RT, Behle JH, Wolf DL, et al. Transcriptomes in healthy
and diseased gingival tissues. J Periodontol 2008;79(11):2112-2124.
53. Papapanou PN, Behle JH, Kebschull M, et al. Subgingival bacterial colonization profiles correlate with gingival tissue gene expression. BMC Microbiol 2009;9:221.
54. Barnes VM, Ciancio SG, Shibly O, et al. Metabolomics reveals
elevated macromolecular degradation in periodontal disease (published online ahead of print Aug. 19, 2011). J Dent Res 2011;90(11):
1293-1297. doi:10.1177/0022034511416240.
55. Bilder L, Machtei EE, Shenhar Y, Kra-Oz Z, Basis F. Salivary
detection of H1N1 virus: a clinical feasibility investigation (published
online ahead of print June 23, 2011). J Dent Res 2011;90(9):1136-1139.
doi:10.1177/0022034511413283.
56. Hart RW, Mauk MG, Liu C, et al. Point-of-care oral-based diagnostics (published online ahead of print April 26, 2011). Oral Dis
2011;17(8):745-752. doi:10.1111/j.1601-0825.2011.01808.x.
57. Slots J, Slots H. Bacterial and viral pathogens in saliva: disease
relationship and infectious risk (published online ahead of print Dec.
7, 2010). Periodontol 2000 2011;55(1):48-69. doi:10.1111/j.1600-0757.
2010.00361.x.
58. Gettig E, Hart TC. Genetics in dental practice: social and ethical
issues surrounding genetic testing. J Dent Educ 2003;67(5):549-562.
59. Eng G, Chen A, Vess T, Ginsburg GS. Genome technologies and
personalized dental medicine (published online ahead of print Dec. 1,
2011). Oral Dis 2012;18(3):223-235. doi:10.1111/j.1601-0825.2011.
01876.x.

60. Eaton S, Collins A, Coulter A, Elwyn G, Grazin N, Roberts S.

Putting patients first. BMJ 2012;344:e2006. doi:10.1136/bmj.e2006.
61. Kornman KS, Duff GW. Personalized medicine: will dentistry
ride the wave or watch from the beach? J Dent Res 2012;91:S8-S11.
62. Karimbux NY, Saraiya VM, Elangovan S, et al. Interleukin-1
gene polymorphisms and chronic periodontitis in adult Caucasians: a
systematic review and meta-analysis (published online ahead of
print Feb. 21, 2012). J Periodontol doi:10.1902/jop.2012.110655.
63. Kornman KS, Crane A, Wang HY, et al. The interleukin-1 genotype as a severity factor in adult periodontal disease. J Clin Periodontol 1997;24(1):72-77.
64. McGuire MK, Nunn ME. Prognosis versus actual outcome, IV:
the effectiveness of clinical parameters and IL-1 genotype in accurately predicting prognoses and tooth survival. J Periodontol 1999;
70(1):49-56.
65. Eickholz P, Kaltschmitt J, Berbig J, Reitmeir P, Pretzl B. Tooth
loss after active periodontal therapy, 1: patient-related factors for
risk, prognosis, and quality of outcome. J Clin Periodontol 2008;
35(2):165-174.
66. Nabors TW, McGlennen RC, Thompson D. Salivary testing for
periodontal disease diagnosis and treatment. Dent Today 2010;29(6):
53-54, 56, 58-60.
67. Demmer RT, Papapanou PN, Jacobs DR Jr, Desvarieux M.
Bleeding on probing differentially relates to bacterial profiles: the
Oral Infections and Vascular Disease Epidemiology Study (published
online ahead of print April 9, 2008). J Clin Periodontol 2008;35(6):
479-486. doi:10.1111/j.1600-051X.2008.01232.x.
68. Kebschull M, Papapanou PN. The use of gene arrays in deciphering the pathobiology of periodontal diseases. Methods Mol Biol
2010;666:385-393.
69. Urdea MS, Neuwald PD, Greenberg BL, et al. Saliva, diagnostics, and dentistry. Adv Dent Res 2011;23(4):353-359.
70. Yager P, Edwards T, Fu E, et al. Microfluidic diagnostic technologies for global public health. Nature 2006;442(7101):412-418.
71. Lee SR, MacCullough C, Chan MM, Leib JR, Davis C, Jacobson
JJ. Salivary diagnostics: a new industryperspectives from business
development, government, regulatory, and payers. Adv Dent Res
2011;23(4):369-374.
72. Ramseier CA, Morelli T, Kinney JS, Dubois M, Rayburn L,
Giannobile W. Salivary diagnostics: periodontal disease. In: Wong D,
ed. Salivary Diagnostics. Ames, Iowa: Wiley-Blackwell; 2008:156-168.
73. Slavkin HC, Fox CH, Meyer DM. Salivary diagnostics and its
impact in dentistry, research, education, and the professional community. Adv Dent Res 2011;23(4):381-386.

JADA 143(10 suppl)

http://jada.ada.org

Copyright 2012 American Dental Association. All rights reserved.

October 2012 11S