Salivary Markers for Periodontal diseases

Introduction

Salivary markers for periodontal diseases are emerging as non-invasive, accessible, and cost-effective tools for the diagnosis, monitoring, and management of periodontal conditions. Saliva contains a variety of biomarkers, including proteins, enzymes, cytokines, and microbial components, which can reflect the health status of periodontal tissues. These markers can be assessed using techniques like enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qPCR) to provide a comprehensive picture of periodontal health. There are several diagnostic kits available for detecting salivary markers, which are useful for diagnosing and monitoring periodontal diseases. In the following discussion we shall read about various salivary biomarkers of periodontal diseases.

C-Reactive Protein (CRP)

C-Reactive Protein (CRP) is a significant biomarker for periodontal disease due to its role in systemic inflammation. Studies have shown that individuals with periodontitis often have elevated serum CRP levels. This elevation is indicative of systemic inflammation triggered by periodontal infection. Also, high CRP levels in periodontitis patients are associated with an increased risk of cardiovascular diseases, cerebrovascular accidents, and adverse pregnancy outcomes like preterm low birth weight. Treating periodontitis can lead to a reduction in CRP levels. It has been demonstrated that Intensive non-surgical periodontal therapy (NSPT) initially increases CRP levels due to acute inflammation but results in a progressive decrease over time. CRP can be used not only to diagnose periodontal disease but also to monitor the effectiveness of periodontal treatments and the overall inflammatory status of the patient (References available in the book).

Interleukins (ILs)

IL-1β

Interleukin-1β (IL-1β) is a well-established biomarker for periodontal diseases due to its significant role in inflammation. is highly effective in diagnosing periodontal disease. IL-1β is a pro-inflammatory cytokine that plays a crucial role in the body’s immune response to infection. Elevated levels of IL-1β in saliva are indicative of an ongoing inflammatory process, which is a hallmark of periodontal disease. Studies have shown that IL-1β has a high sensitivity and specificity for distinguishing between healthy individuals and those with periodontitis. For instance, IL-1β exhibited an area under the curve (AUC) value of 0.88 with 90% sensitivity and 76% specificity for discriminating periodontitis subjects from healthy subjects. Higher levels of IL-1β are associated with increased severity of periodontal disease. This makes it a valuable marker not only for diagnosis but also for monitoring disease progression and response to treatment. The diagnostic accuracy of IL-1β can be enhanced when combined with other biomarkers such as Matrix Metalloproteinase-8 (MMP-8) and Porphyromonas gingivalis (Pg). This combination improves the ability to differentiate between various stages of periodontal disease (References available in the book).

IL-6

Interleukin-6 (IL-6) is a significant biomarker for periodontal diseases due to its role in inflammation and immune response. IL-6 is a pleiotropic cytokine involved in both local and systemic inflammatory processes. It plays a crucial role in the pathogenesis of periodontal disease by promoting inflammation and bone resorption. Elevated levels of IL-6 in gingival crevicular fluid (GCF) and serum are associated with periodontal disease. Measuring IL-6 levels can help in diagnosing periodontal disease and assessing its severity. IL-6 is not only a marker for periodontal disease but also links oral health with systemic conditions. High IL-6 levels in periodontal patients are associated with increased risks of systemic diseases such as cardiovascular disease and diabetes. It has been demonstrated that effective periodontal treatment can reduce IL-6 levels, indicating a decrease in inflammation and improvement in periodontal health.

Tumor Necrosis Factor-alpha (TNF-α)

TNF-α is a crucial biomarker for periodontal diseases due to its role in inflammation and immune response. It is a potent pro-inflammatory cytokine produced primarily by macrophages and monocytes. It plays a significant role in the inflammatory response associated with periodontal disease. Elevated levels of TNF-α in gingival crevicular fluid (GCF) and saliva are indicative of periodontal inflammation. Studies have shown that TNF-α levels are significantly higher in individuals with periodontitis compared to healthy individuals. Higher levels of TNF-α are associated with increased severity of periodontal disease. This makes it a valuable marker for assessing disease progression and the effectiveness of periodontal treatments. TNF-α is also linked to systemic conditions such as cardiovascular diseases and diabetes. Elevated TNF-α levels in periodontal patients can indicate a higher risk of these systemic diseases.

Matrix Metalloproteinases (MMPs)

MMP-8

Matrix Metalloproteinase-8 (MMP-8) is a key biomarker for periodontal diseases due to its role in the degradation of extracellular matrix components. MMP-8, also known as collagenase-2, is primarily involved in the breakdown of type I collagen, which is a major component of the periodontal ligament. Elevated levels of MMP-8 in gingival crevicular fluid (GCF) and saliva are indicative of active periodontal tissue destruction. MMP-8 is considered one of the most reliable biomarkers for diagnosing periodontal disease. Studies have shown that measuring active MMP-8 (aMMP-8) levels in oral fluids can effectively differentiate between healthy and diseased periodontal tissues. Recent advancements have led to the development of point-of-care tests for aMMP-8, allowing for rapid and non-invasive diagnosis of periodontal disease. These tests utilize oral fluids such as GCF, saliva, and mouth rinse, making them convenient for clinical use. MMP-8 levels can also be used to monitor the progression of periodontal disease and the effectiveness of treatment. A decrease in MMP-8 levels after periodontal therapy indicates a reduction in tissue destruction and inflammation.

MMP-9

Matrix Metalloproteinase-9 (MMP-9) is another important biomarker for periodontal diseases due to its role in tissue remodeling and inflammation. MMP-9, also known as gelatinase B, is involved in the degradation of gelatin and type IV collagen, which are components of the extracellular matrix. Elevated levels of MMP-9 in gingival crevicular fluid (GCF) and saliva are indicative of periodontal tissue destruction. MMP-9 is considered a valuable biomarker for diagnosing periodontal disease. Studies have shown that salivary MMP-9 levels are significantly higher in individuals with periodontitis compared to healthy individuals. MMP-9 levels can be used to monitor the inflammatory status of periodontal tissues. Higher levels of MMP-9 are associated with increased inflammation and tissue breakdown, making it a useful marker for assessing disease severity and progression. Research has indicated that salivary MMP-9 is a sensitive marker for periodontal inflammation during orthodontic treatment. This highlights its potential in reducing periodontal hazards during such treatments (References available in the book). MMP-9’s role as a biomarker underscores its importance in both the diagnosis and management of periodontal diseases.

Osteoprotegerin (OPG)

It is a significant biomarker for periodontal diseases due to its role in bone metabolism and regulation. OPG is a glycoprotein that acts as a decoy receptor for the receptor activator of nuclear factor-kappa B ligand (RANKL). By binding to RANKL, OPG prevents it from interacting with its receptor RANK on osteoclasts, thereby inhibiting osteoclastogenesis and bone resorption. The RANKL/OPG ratio is a critical indicator of bone resorption activity. In periodontal disease, this ratio is often elevated due to increased RANKL and decreased OPG levels, indicating active bone loss. OPG levels are influenced by inflammatory cytokines. In periodontitis, the inflammatory environment can lead to altered OPG expression, contributing to the imbalance in bone remodeling. Monitoring OPG levels can help assess the effectiveness of periodontal treatments. Successful treatment often leads to normalization of the RANKL/OPG ratio, reflecting reduced bone resorption and inflammation. OPG’s role as a biomarker underscores its importance in both the diagnosis and management of periodontal diseases.

Lactoferrin

Lactoferrin is a promising biomarker for periodontal diseases due to its antimicrobial and anti-inflammatory properties. Lactoferrin is a glycoprotein with strong antimicrobial properties. It helps in controlling bacterial growth and maintaining oral health by binding to iron, which bacteria need to thrive. Elevated levels of lactoferrin in saliva and gingival crevicular fluid (GCF) are associated with periodontal inflammation. This makes it a useful marker for detecting and monitoring periodontal disease. Studies have shown that lactoferrin levels are significantly higher in individuals with periodontitis compared to healthy individuals. This correlation helps in assessing the severity of the disease. Lactoferrin can be measured using non-invasive methods such as saliva tests. This makes it a convenient and effective biomarker for early detection and monitoring of periodontal disease. Lactoferrin’s role as a biomarker highlights its potential in improving the diagnosis and management of periodontal diseases.

Pyridinoline Cross-Linked Carboxyterminal Telopeptide of Type I Collagen (ICTP)

ICTP is a valuable biomarker for periodontal diseases due to its association with bone resorption. It is a degradation product of type I collagen, which is a major component of bone. Elevated levels of ICTP in saliva and gingival crevicular fluid (GCF) indicate increased bone resorption, a hallmark of periodontal disease. Studies have shown that ICTP levels are significantly higher in individuals with periodontitis compared to those with gingivitis or healthy periodontal tissues. This makes ICTP a useful marker for diagnosing and monitoring periodontal disease. Higher ICTP levels are associated with more severe periodontal disease. This correlation helps in assessing the extent of bone loss and the progression of the disease. The diagnostic accuracy of ICTP can be enhanced when combined with other biomarkers such as Interleukin-1β (IL-1β) and Matrix Metalloproteinase-8 (MMP-8). This combination improves the ability to differentiate between various stages of periodontal disease.

Porphyromonas gingivalis-specific DNA or RNA

Porphyromonas gingivalis (P. gingivalis) is a key pathogen in periodontal disease, and its specific DNA or RNA can serve as a valuable biomarker. The presence of P. gingivalis-specific DNA or RNA in saliva or gingival crevicular fluid (GCF) is a strong indicator of periodontal infection. Techniques such as polymerase chain reaction (PCR) and quantitative PCR (qPCR) are commonly used to detect these genetic markers. Studies have shown that detecting P. gingivalis-specific DNA or RNA has high sensitivity and specificity for diagnosing periodontal disease. This makes it a reliable method for identifying the presence of this pathogen. The quantity of P. gingivalis-specific DNA or RNA can correlate with the severity of periodontal disease. Higher levels are often associated with more advanced stages of the disease. Measuring P. gingivalis-specific DNA or RNA levels before and after periodontal treatment can help assess the effectiveness of the therapy. A significant reduction in these levels typically indicates successful treatment.

Immunoglobulin A

Immunoglobulin A (IgA) is an important biomarker for periodontal diseases due to its role in the immune response. IgA is the predominant antibody found in mucosal secretions, including saliva. It plays a crucial role in the immune defense against periodontal pathogens by preventing their adherence to oral tissues and neutralizing their toxins. Studies have shown that levels of salivary IgA are elevated in individuals with periodontal disease compared to healthy individuals. This increase is a response to the presence of periodontal pathogens. Measuring salivary IgA levels can help in diagnosing periodontal disease. Elevated IgA levels in saliva can indicate an ongoing immune response to periodontal infection. IgA levels can also be used to monitor the progression of periodontal disease and the effectiveness of treatment. Changes in IgA levels can reflect the body’s response to periodontal therapy.

Current research and available diagnostic kits

Salivary diagnostic kits for periodontal diseases are designed to detect specific biomarkers associated with the presence and severity of periodontal conditions. These kits provide a non-invasive and convenient method for early diagnosis, monitoring disease progression, and evaluating treatment efficacy.

PerioSafe®

PerioSafe® is a chairside diagnostic test that measures active-matrix metalloproteinase-8 (aMMP-8), an enzyme associated with periodontal tissue destruction. The test provides results within minutes and helps in assessing the risk of active periodontal disease. It helps in early detection of periodontal disease, monitoring disease activity, and evaluating treatment success.

ORALyzer®

ORALyzer® is a point-of-care diagnostic device that measures multiple biomarkers in saliva, including inflammatory cytokines and enzymes. It uses a microfluidic chip technology to provide rapid and accurate results. It is used for comprehensive assessment of periodontal health, personalized treatment planning, and monitoring treatment outcomes.

OraRisk®

OraRisk® is a salivary DNA test that identifies specific bacteria associated with periodontal disease. It analyzes the presence and quantity of pathogenic bacteria using polymerase chain reaction (PCR) technology. It is used for identifying bacterial profiles to tailor periodontal therapy, assessing the risk of disease progression, and monitoring microbial changes during treatment.

Saliva-Check BUFFER

Saliva-Check BUFFER assesses salivary parameters such as pH, buffering capacity, and flow rate. While it is not specific to periodontal disease, it provides valuable information about the oral environment, which can influence periodontal health. It is used for evaluating oral health status, assessing risk factors for periodontal disease, and guiding preventive measures.

Future of salivary diagnostic kits for identification of periodontal disease activity

Integration of Advanced Technologies

The use of nanotechnology, biosensors, and microfluidics is enhancing the sensitivity and specificity of salivary diagnostic kits. These technologies allow for the detection of multiple biomarkers simultaneously, providing a comprehensive assessment of periodontal health.

Point-of-Care Testing

The development of portable, chairside diagnostic kits is making it easier for clinicians to diagnose periodontal disease quickly and accurately. These point-of-care tests can provide immediate results, facilitating timely intervention and treatment.

Combination of Biomarkers

Future diagnostic kits are likely to combine multiple biomarkers, such as cytokines, enzymes, and microbial DNA, to improve diagnostic accuracy. This multi-marker approach can help in differentiating between various stages of periodontal disease and monitoring disease progression.

Personalized Medicine

Advances in salivary diagnostics are contributing to the field of personalized medicine. By analyzing an individual’s specific biomarker profile, clinicians can tailor treatment plans to address the unique needs of each patient, improving outcomes.

Regulatory Approvals and Clinical Adoption

While there are currently no FDA-approved salivary diagnostic tests for periodontal disease, ongoing research and clinical trials are expected to lead to regulatory approvals in the near future. This will facilitate wider adoption of these diagnostic tools in clinical practice.

Research and Collaboration

Continued research and collaboration between dental researchers, clinicians, and technology developers are essential for overcoming current challenges and advancing the field of salivary diagnostics. Collaborative efforts can lead to the development of more robust and reliable diagnostic kits

Conclusion

Salivary biomarkers have become very useful biomarkers for identification of periodontal disease activity. These markers can be assessed using various techniques like enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qPCR) to provide a comprehensive picture of periodontal health. The kits designed to measure various biomarkers in saliva, providing valuable insights into periodontal health and other systemic conditions. The future of salivary diagnostic kits for periodontal disease activity looks promising, with advancements in technology and research paving the way for more accurate, non-invasive, and convenient diagnostic tools.

References

References are available in the hardcopy of the website “Periobasics: A Textbook of Periodontics and Implantology”.