A Diagnostic & Prognostic Biofluid

A Diagnostic & Prognostic Biofluid for Periodontal Disease

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Saliva:

A Diagnostic & Prognostic Biofluid for Periodontal Disease

Introduction

So,  where does one begin when talking about periodontal disease? There are volumes and volumes of clinical studies and research papers on the topic: enough to become totally confused with all of the information that is out there.

Let’s begin by reviewing a basic medical model that we all learned about diseases and infections that we should apply to periodontal diseases/infections/inflammatory diseases:

1. Determine the Cause

2. Treat the Cause

3. Monitor the results

4. Change the course of treatment if treatment does not eliminate or reduce the  disease process.

This basic medical strategy, while used in medicine, has not been used in oral medicine. One might argue that “biofilm” is the cause. However, this argument would fail within this medical model since we cannot “see” microscopic causation and “biofilm” is a very general term. Most of us did not learn that there are very specific pathogenic microorganisms that are the true causative agents of these inflammatory events we call periodontal disease: gingivitis and periodontitis. By definition, periodontal diseases are “inflammatory diseases of the supporting tissues of the teeth caused by the immune responseto specific microorganisms or groups of specific organisms, resulting in progressive destruction of the periodontal ligament and alveolar bone with pocket formation, recession, or  both.”1 While the mouth harbors hundreds of different species of bacteria, only a relative few bear the “weight of evidence” as being initiators and sustainers of this inflammatory process.2 This is important to know: certain microorganisms have a greater capacity, or virulence, to initiate both the innate immune response as well as the adaptive immune response.3 Each person tends to have different causative agents at different concentrations (inflammatory burden).4 Then, if you add modifying factors such as genetic differences, smoking, diabetes, medications, etc., we can see that periodontal diseases are very personal.5 Periodontal disease is also considered “as a complex genetic disease whose phenotype is determined by both the genetic makeup of the individual and the environmental influences on the affected individual.6 Thus, there are genetic factors as well as additional modifying factors that contribute to the severity of the disease.

Notice the three important parts to these definitions:

1. Inflammatory disease

2. Caused by the host’s immune response to specificmicroorganisms or groups of specific bacteria

3. Complex genetic disease

So, with this new understanding of periodontal disease, what do we talk about and how do we approach these potentially serious infections? Get a group of 30 dental professionals together to discuss their approach to periodontal disease diagnosis and their preferred treatment regimen and you’ll inevitably wind up with 30 different answers of varying degrees. And most of the discussion will be about technique. In fact, it would be highly unusual to have someone actually discuss the real etiology and pathogenesis of periodontal disease: the two most important aspects of the initiation and progression of these very different disease states. Why is this true? Because we were not trained to do this. And yet, the science is now there to approach this disease in as sophisticated a manner as other infectious diseases are diagnosed in other areas of medicine. One of the most respected researchers on oral infections wrote over a decade ago: “The ultimate risk factor for any infectious disease is the causative agent of that disease.”7 Another wrote: “Without bacterial agents, these disease states cannot  exist.”8 What simple, yet profound, statements of truth. Even today, with decades of research to support the etiology and pathogenesis of these  infections, most clinicians accept the age-old adage of “clinical signs” and the generic definition of plaque or biofilm as the “Holy Grail” of determining who has periodontal disease and what the severity of that disease is. In medicine, this would be thought of as archaic. We can find great value in using the clinical laboratory model to determine the exact nature of each infection and determine who requires true periodontal therapy vs. who merely needs a prophy. The use of the medical model of microbial and genetic diagnosis in conjunction with clinical presentation is here to stay, both in medicine and now oral medicine. This concept determines who is at risk for more disease and more severe disease9anddrives more successful therapy.

We cannot continue to diagnose these disease states using only clinical signs, and ignore the underlying biologic phenotype. While clinical signs are used in medicine, the physician does not stop there. Clinical laboratory medicine through diagnostic and prognostic testing is vital to the prevention and diagnosis of all disease states.

Modern medicine’s diagnostic litmus test

Physicians rely heavily on the detailed and specific information from body fluids prior to a “working” diagnosis.  The doctor

will typically measure and assess some of the typical “barometers” of overall health, such as taking the patient’s blood pressure reading, listening to his chest with a stethoscope, and recording his weight. The doctor records the clinical findings, and may be thinking that this patient is at risk based on these findings. However, prior to any therapeutic protocol, the doctor orders specific blood tests to confirm or not confirm the “preliminary” diagnosis. The clinical exam, while important and necessary, does

not complete the fact-finding process. Thus, specific laboratory blood tests are run to determine a more complete risk profile for each patient. When the test results return, only then is the physician armed with a comprehensive physical and biological profile. Now, the physician can objectively make clinical decisions based on facts, not subjectivity. Wouldn’t it be beneficial if dental professionals had access to such definitive tests for conditions such as periodontal disease and other oral diseases? Well, we now have access to the same 21st century diagnostic tools that physicians use, and they don’t require blood.

Salivary diagnostics in dentistry

Today, dental professionals have access to two saliva-based laboratory tests that analyze the DNA content present in patients’ saliva. The MyPerioPath®test can provide clinicians with specific details of a patient’s periodontal disease, including a comprehensive list of the pathogenic bacteria present, as well as the quantity, or bacterial “threshold” that helps determine the risk of disease and disease progression.2 This test report serves as a blueprint for determining the most appropriate and efficacious treatment plan. MyPerioID® PST® is a genetic risk-assessment test that analyzes two human genes ( IL-1 A & IL-1 β) for variations that can help identify an individual’s predisposition for over-expression of inflammation and increased risk for more severe periodontal disease.5 This genetic test complements the bacterial DNA testing by providing insight into the person’s individual inflammatory response to specific pathogenic bacteria. While the clinical presentation of disease tells us that

infection exists, it alone cannot determine the causative agents or demonstrate whether our therapy did, in fact, eliminate or reduce the causative agents. Clinical signs are a measurement of the damage from a disease process that has already occurred. These signs do not tell us the types of bacteria present, the inflammatory burden based on bacterial load, or the genetic differences that may exist in one patient vs. another. Knowledge of this information is essential to determining the need for therapy, the potential need for antimicrobial therapy as an adjunct to the physical removal of biofilm, the severity of the infection, and/or the potential for disease progression after therapy.

The biofluid of choice for dentistry

 As a clinical medium, saliva has exciting uses today in oral medicine. The ability to use saliva to obtain valuable biological information is a major break-through in our ability to diagnose more accurately and to treat more specifically. Saliva is easy to collect, store, and ship, and only a small quantity is required for analysis. The non-invasive collection procedure reveals

biological information that is imperative to understanding disease both at the time of diagnosis and as a “control analysis” to determine whether therapy has reduced the risk for disease progression. 

The future of salivary diagnostics in dentistry

Rapidly emerging science is closing the gap between saliva and other diagnostic biomedia, such as blood, urine, fecal matter, cerebrospinal fluid, and tears. Easily and non-invasively collected, saliva contains volumes of genomic and proteomic diagnostic information that can mark human diseases with great sensitivity and specificity. With a saliva test, a result report is generated that provides biological information that helps to complete the picture of the examination process. No longer will we have to “guess” when a physician asks for medical clearance prior to medical surgical procedures. Hopefully, the reader can see the possibilities for how saliva and its biological information can help improve diagnosis and treatment for periodontal

infections, and future uses as well. We know how to remove plaque, biofilm, and calculus, and have a number of different “art forms” that we can use. However, there is no single therapy that works every time, because not all patients are alike. The ability to use modern science to personalize therapy based on patient needs makes sense. We have nothing to lose by bringing the clinical laboratory model into our profession, and everything to gain. This is an important step toward bringing the entire dental profession into a significant relationship with medicine in general.

References:

1. Newman M, Carranza F, Takei H, eds. Clinical  Periodontology, 9th ed. Philadelphia, PA: W.B. Saunders Co.; 2002:67.

2. Teles RP, Haffajee AD, Socransky SS. Microbiological goals of periodontal therapy. Periodontol 2000.

2006;42:180-218.

3.Offenbacher S, Barros SP, Beck JD. Rethinking periodontal inflammation. 2008  Aug;79(8 Suppl):1577-1584.

4.Haffajee AD, Teles RP, Socransky SS. The effect of periodontal therapy on the composition of the subgingival microbiota. Periodontol 2000. 2006;42:219-258.

5.Graves D. Cytokines that promote periodontal tissue destruction. J Periodontol. 2008 Aug;79(8Suppl):1585-1591.

6.Yoshie H, Kobayashi T, Tai H, Galicia JC. The role of genetic polymorphisms in periodontitis. 2007;43:102-132.

7.Haffajee AD, Socransky SS. Microbial etiological agents of destructive periodontal diseases. Periodontol

2000. 1994 Jun;5:78-111.

8. Bartold PM, Narayanan AS. Biology of the Periodontal Connective Tissues. Chicago, IL: Quintessence Publishing;1998.

9. van Winkelhoff AJ, Winkel EG. Microbiological diagnostics in periodontics: biological significance and clinical validity. Periodontol 2000. 2005; 39:40-52.

10. Mombelli A. Microbiology and antimicrobial therapy of peri-implantitis. Periodontol 2000.2002;28:177-189.

11. Paju S, Pussinen PJ, Suominen-Taipale L, et al. Detection of multiple pathogenic species in saliva is associated with periodontal infection in adults. J Clin Microbiol. 2009 Jan;47(1):235-238.

12.Romanenko VG, Melvin JE. Salivary gland physiology relevant to diagnostics. In: Wong D, ed. Salivary Diagnostics. Hoboken, NJ: Wiley-Blackwell; 2008:14-27.

13. Li Y, Elashoff D, Oh M, et al. Serum circulating human mRNA profiling and its  utility for oral cancer detection. J

Clin Oncol. 2006 Apr 10;24(11):1754-1760.

14. St John MA, Li Y, Zhou X, et al. Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2004 Aug;130(8):929-935.

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