Effects of Smoking on the Etiology and Pathogenesis of Periodontal Disease

Smoking is a significant risk factor for the development and progression of periodontal disease. It affects various aspects of periodontal health, including microbiology, immunology, and physiology. Understanding these effects is crucial for dental professionals in managing patients with periodontal disease, particularly those who smoke.

Etiologic Factors and the Impact of Smoking

1. Microbiology

   • Plaque Accumulation:
     • Smoking does not affect the rate of plaque accumulation on teeth. This means that smokers may have similar levels of plaque as non-smokers.
   • Colonization of Periodontal Pathogens:
     • Smoking increases the colonization of shallow periodontal pockets by periodontal pathogens. This can lead to an increased risk of periodontal disease.
     • There are higher levels of periodontal pathogens found in deep periodontal pockets among smokers, contributing to the severity of periodontal disease.

2. Immunology

   • Neutrophil Function:
     • Smoking alters neutrophil chemotaxis (the movement of neutrophils towards infection), phagocytosis (the process by which neutrophils engulf and destroy pathogens), and the oxidative burst (the rapid release of reactive oxygen species to kill bacteria).
   • Cytokine Levels:
     • Increased levels of pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Prostaglandin E2 (PGE2) are found in the gingival crevicular fluid (GCF) of smokers. These cytokines play a role in inflammation and tissue destruction.
   • Collagenase and Elastase Production:
     • There is an increase in neutrophil collagenase and elastase in GCF, which can contribute to the breakdown of connective tissue and exacerbate periodontal tissue destruction.
   • Monocyte Response:
     • Smoking enhances the production of PGE2 by monocytes in response to lipopolysaccharides (LPS), further promoting inflammation and tissue damage.

3. Physiology

   • Gingival Blood Vessels:
     • Smoking leads to a decrease in gingival blood vessels, which can impair the delivery of immune cells and nutrients to the periodontal tissues, exacerbating inflammation.
   • Gingival Crevicular Fluid (GCF) Flow:
     • There is a reduction in GCF flow and bleeding on probing, even in the presence of increased inflammation. This can mask the clinical signs of periodontal disease, making diagnosis more challenging.
   • Subgingival Temperature:
     • Smoking is associated with a decrease in subgingival temperature, which may affect the metabolic activity of periodontal pathogens.
   • Recovery from Local Anesthesia:
     • Smokers may require a longer time to recover from local anesthesia, which can complicate dental procedures and patient management.

Clinical Implications

1. Increased Risk of Periodontal Disease:

   • Smokers are at a higher risk for developing periodontal disease due to the combined effects of altered microbial colonization, impaired immune response, and physiological changes in the gingival tissues.

2. Challenges in Diagnosis:

   • The reduced bleeding on probing and altered GCF flow in smokers can lead to underdiagnosis or misdiagnosis of periodontal disease. Dental professionals must be vigilant in assessing periodontal health in smokers.

3. Treatment Considerations:

   • Smoking cessation should be a key component of periodontal treatment plans. Educating patients about the effects of smoking on periodontal health can motivate them to quit.
   • Treatment may need to be more aggressive in smokers due to the increased severity of periodontal disease and the altered healing response.

4. Monitoring and Maintenance:

   • Regular monitoring of periodontal health is essential for smokers, as they may experience more rapid disease progression. Tailored maintenance programs should be implemented to address their specific needs.

Flossing Technique

Flossing is an essential part of oral hygiene that helps remove plaque and food particles from between the teeth and along the gumline, areas that toothbrushes may not effectively clean. Proper flossing technique is crucial for maintaining gum health and preventing cavities.

Flossing Technique

1. Preparation:

   • Length of Floss: Take 12 to 18 inches of dental floss. This length allows for adequate maneuverability and ensures that you can use a clean section of floss for each tooth.
   • Grasping the Floss: Hold the floss taut between your hands, leaving a couple of inches of floss between your fingers. This tension helps control the floss as you maneuver it between your teeth.

2. Inserting the Floss:

   • Slip Between Teeth: Gently slide the floss between your teeth. Be careful not to snap the floss, as this can cause trauma to the gums.
   • Positioning: Insert the floss into the area between your teeth and gums as far as it will comfortably go, ensuring that you reach the gumline.

3. Flossing Motion:

   • Vertical Strokes: Use 8 to 10 vertical strokes with the floss to dislodge food particles and plaque. Move the floss up and down against the sides of each tooth, making sure to clean both the front and back surfaces.
   • C-Shaped Motion: For optimal cleaning, wrap the floss around the tooth in a C-shape and gently slide it beneath the gumline.

4. Frequency:

   • Daily Flossing: Aim to floss at least once a day. Consistency is key to maintaining good oral hygiene.
   • Best Time to Floss: The most important time to floss is before going to bed, as this helps remove debris and plaque that can accumulate throughout the day.

5. Flossing and Brushing:

   • Order of Operations: Flossing can be done either before or after brushing your teeth. Both methods are effective, so choose the one that fits best into your routine.

Periodontal Bone Grafts

Bone grafting is a critical procedure in periodontal surgery, aimed at restoring lost bone and supporting the regeneration of periodontal tissues.

1. Bone Blend

 Bone blend is a mixture of cortical or cancellous bone that is procured using a trephine or rongeurs, placed in an amalgam capsule, and triturated to achieve a slushy osseous mass. This technique allows for the creation of smaller particle sizes, which enhances resorption and replacement with host bone.

Particle Size: The ideal particle size for bone blend is approximately 210 x 105 micrometers.

Rationale: Smaller particle sizes improve the chances of resorption and integration with the host bone, making the graft more effective.

2. Types of Periodontal Bone Grafts

A. Autogenous Grafts

Autogenous grafts are harvested from the patient’s own body, providing the best compatibility and healing potential.

1. Cortical Bone Chips

   • History: First used by Nabers and O'Leary in 1965.
   • Characteristics: Composed of shavings of cortical bone removed during osteoplasty and ostectomy from intraoral sites.
   • Challenges: Larger particle sizes can complicate placement and handling, and there is a potential for sequestration. This method has largely been replaced by autogenous osseous coagulum and bone blend.

2. Osseous Coagulum and Bone Blend

   • Technique: Intraoral bone is obtained using high- or low-speed round burs and mixed with blood to form an osseous coagulum (Robinson, 1969).
   • Advantages: Overcomes disadvantages of cortical bone chips, such as inability to aspirate during collection and variability in quality and quantity of collected bone.
   • Applications: Used in various periodontal procedures to enhance healing and regeneration.

3. Intraoral Cancellous Bone and Marrow

   • Sources: Healing bony wounds, extraction sockets, edentulous ridges, mandibular retromolar areas, and maxillary tuberosity.
   • Applications: Provides a rich source of osteogenic cells and growth factors for bone regeneration.

4. Extraoral Cancellous Bone and Marrow

   • Sources: Obtained from the anterior or posterior iliac crest.
   • Advantages: Generally offers the greatest potential for new bone growth due to the abundance of cancellous bone and marrow.

B. Bone Allografts

Bone allografts are harvested from donors and can be classified into three main types:

1. Undermineralized Freeze-Dried Bone Allograft (FDBA)

   • Introduction: Introduced in 1976 by Mellonig et al.
   • Process: Freeze drying removes approximately 95% of the water from bone, preserving morphology, solubility, and chemical integrity while reducing antigenicity.
   • Efficacy: FDBA combined with autogenous bone is more effective than FDBA alone, particularly in treating furcation involvements.

2. Demineralized (Decalcified) FDBA

   • Mechanism: Demineralization enhances osteogenic potential by exposing bone morphogenetic proteins (BMPs) in the bone matrix.
   • Osteoinduction vs. Osteoconduction: Demineralized grafts induce new bone formation (osteoinduction), while undermineralized allografts facilitate bone growth by providing a scaffold (osteoconduction).

3. Frozen Iliac Cancellous Bone and Marrow

   • Usage: Used sparingly due to variability in outcomes and potential complications.

Comparison of Allografts and Alloplasts

• Clinical Outcomes: Both FDBA and DFDBA have been compared to porous particulate hydroxyapatite, showing little difference in post-treatment clinical parameters.
• Histological Healing: Grafts of DFDBA typically heal with regeneration of the periodontium, while synthetic bone grafts (alloplasts) heal by repair, which may not restore the original periodontal architecture.

Components of Gingival Crevicular Fluid (GCF) and Matrix Metalloproteinases (MMPs)

Gingival crevicular fluid (GCF) is a serum-like fluid found in the gingival sulcus that plays a significant role in periodontal health and disease. Understanding its composition, particularly glucose and protein content, as well as the role of matrix metalloproteinases (MMPs) in tissue remodeling, is essential for dental professionals.

Composition of Gingival Crevicular Fluid (GCF)

1. Glucose and Hexosamines:

   • GCF contains compounds such as glucose, hexosamines, and hexuronic acid.
   • Glucose Levels:
     • Blood glucose levels do not correlate with GCF glucose levels; in fact, glucose concentration in GCF is three to four times greater than that in serum.
     • This elevated glucose level is interpreted as a result of the metabolic activity of adjacent tissues and the influence of local microbial flora.

2. Protein Content:

   • The total protein content of GCF is significantly less than that of serum.
   • This difference in protein concentration reflects the unique environment of the gingival sulcus and the specific functions of GCF in periodontal health.

Matrix Metalloproteinases (MMPs)

1. Definition and Function:

   • MMPs are a family of proteolytic enzymes that degrade extracellular matrix molecules, including collagen, gelatin, and elastin.
   • They are produced by various cell types, including:
     • Neutrophils
     • Macrophages
     • Fibroblasts
     • Epithelial cells
     • Osteoblasts and osteoclasts

2. Classification:

   • MMPs are classified based on their substrate specificity, although it is now recognized that many MMPs can degrade multiple substrates. The classification includes:
     • Collagenases: e.g., MMP-1 and MMP-8 (break down collagen)
     • Gelatinases: Type IV collagenases
     • Stromelysins
     • Matrilysins
     • Membrane-type metalloproteinases
     • Others

3. Activation and Inhibition:

   • MMPs are secreted in an inactive form (latent) and require proteolytic cleavage for activation. This activation is facilitated by proteases such as cathepsin G produced by neutrophils.
   • Inhibitors: MMPs are regulated by proteinase inhibitors, which possess anti-inflammatory properties. Key inhibitors include:
     • Serum Inhibitors:
       • α1-antitrypsin
       • α2-macroglobulin (produced by the liver, inactivates various proteinases)
     • Tissue Inhibitors:
       • Tissue inhibitors of metalloproteinases (TIMPs), with TIMP-1 being particularly important in periodontal disease.
   • Antibiotic Inhibition: MMPs can also be inhibited by tetracycline antibiotics, leading to the development of sub-antimicrobial formulations of doxycycline as a systemic adjunctive treatment for periodontitis, exploiting its anti-MMP properties.

Merkel Cells

1. Location and Function:
   • Merkel cells are located in the deeper layers of the epithelium and are associated with nerve endings.
   • They are connected to adjacent cells by desmosomes and are identified as tactile receptors.
   • These cells play a role in the sensation of touch and pressure, contributing to the sensory functions of the oral mucosa.

Clinical Implications

1. GCF Analysis:

   • The composition of GCF, including glucose and protein levels, can provide insights into the inflammatory status of the periodontal tissues and the presence of periodontal disease.

2. Role of MMPs in Periodontal Disease:

   • MMPs are involved in the remodeling of periodontal tissues during inflammation and disease progression. Understanding their regulation and activity is crucial for developing therapeutic strategies.

3. Therapeutic Applications:

   • The use of sub-antimicrobial doxycycline as an adjunctive treatment for periodontitis highlights the importance of MMP inhibition in managing periodontal disease.

4. Sensory Function:

   • The presence of Merkel cells in the gingival epithelium underscores the importance of sensory feedback in maintaining oral health and function.

Periodontal Diseases Associated with Neutrophil Disorders

1. Acute Necrotizing Ulcerative Gingivitis (ANUG)

   • Description: A severe form of gingivitis characterized by necrosis of the interdental papillae, pain, and foul odor.
   • Association: Neutrophil dysfunction can exacerbate the severity of ANUG, leading to rapid tissue destruction.

2. Localized Juvenile Periodontitis

   • Description: A form of periodontitis that typically affects adolescents and is characterized by localized bone loss around the permanent teeth.
   • Association: Impaired neutrophil function contributes to the pathogenesis of this condition.

3. Prepubertal Periodontitis

   • Description: A rare form of periodontitis that occurs in children before puberty, leading to rapid attachment loss and bone destruction.
   • Association: Neutrophil disorders can play a significant role in the development and progression of this disease.

4. Rapidly Progressive Periodontitis

   • Description: A form of periodontitis characterized by rapid attachment loss and bone destruction, often occurring in young adults.
   • Association: Neutrophil dysfunction may contribute to the aggressive nature of this disease.

5. Refractory Periodontitis

   • Description: A form of periodontitis that does not respond to conventional treatment and continues to progress despite therapy.
   • Association: Neutrophil disorders may be implicated in the persistent nature of this condition.

Bacterial Properties Involved in Evasion of Host Defense Mechanisms

Bacteria have evolved various strategies to evade the host's immune defenses, allowing them to persist and cause disease. Understanding these mechanisms is crucial for developing effective treatments and preventive measures against bacterial infections, particularly in the context of periodontal disease. This lecture will explore the bacterial species involved, their properties, and the biological effects of these properties on host defense mechanisms.

Host Defense Mechanisms and Bacterial Evasion Strategies

1. Specific Antibody Evasion

   • Bacterial Species:
     • Porphyromonas gingivalis
     • Prevotella intermedia
     • Prevotella melaninogenica
     • Capnocytophaga spp.
   • Bacterial Property:
     • IgA- and IgG-degrading proteases
   • Biologic Effect:
     • Degradation of specific antibodies, which impairs the host's ability to mount an effective immune response against these bacteria.

2. Evasion of Polymorphonuclear Leukocytes (PMNs)

   • Bacterial Species:
     • Aggregatibacter actinomycetemcomitans
     • Fusobacterium nucleatum
     • Porphyromonas gingivalis
     • Treponema denticola
   • Bacterial Properties:
     • Leukotoxin: A toxin that can induce apoptosis in PMNs.
     • Heat-sensitive surface protein: May interfere with immune recognition.
     • Capsule: A protective layer that inhibits phagocytosis.
     • Inhibition of superoxide production: Reduces the oxidative burst necessary for bacterial killing.
   • Biologic Effects:
     • Inhibition of PMN function, leading to decreased bacterial killing.
     • Induction of apoptosis (programmed cell death) in PMNs, reducing the number of immune cells available to fight infection.
     • Inhibition of phagocytosis, allowing bacteria to evade clearance.

3. Evasion of Lymphocytes

   • Bacterial Species:
     • Aggregatibacter actinomycetemcomitans
     • Fusobacterium nucleatum
     • Tannerella forsythia
     • Prevotella intermedia
   • Bacterial Properties:
     • Leukotoxin: Induces apoptosis in lymphocytes.
     • Cytolethal distending toxin: Affects cell cycle progression and induces cell death.
     • Heat-sensitive surface protein: May interfere with immune recognition.
     • Cytotoxin: Directly damages immune cells.
   • Biologic Effects:
     • Killing of mature B and T cells, leading to a weakened adaptive immune response.
     • Nonlethal suppression of lymphocyte activity, impairing the immune response.
     • Impairment of lymphocyte function by arresting the cell cycle, leading to decreased responses to antigens and mitogens.
     • Induction of apoptosis in mononuclear cells and lymphocytes, further reducing immune capacity.

4. Inhibition of Interleukin-8 (IL-8) Production

   • Bacterial Species:
     • Porphyromonas gingivalis
   • Bacterial Property:
     • Inhibition of IL-8 production by epithelial cells.
   • Biologic Effect:
     • Impairment of PMN response to bacteria, leading to reduced recruitment and activation of neutrophils at the site of infection.