Periodontal Medicaments

Periodontal diseases often require adjunctive therapies to traditional mechanical treatments such as scaling and root planing. Various medicaments have been developed to enhance the healing process and control infection in periodontal tissues. This lecture will discuss several periodontal medicaments, their compositions, and their clinical applications.

1. Elyzol

• Composition:
  • Elyzol is an oil-based gel containing 25% metronidazole. It is formulated with glyceryl mono-oleate and sesame oil.
• Clinical Use:
  • Elyzol has been found to be equivalent to scaling and root planing in terms of effectiveness for treating periodontal disease.
  • However, no adjunctive effects beyond those achieved with mechanical debridement have been demonstrated.

2. Actisite

• Composition:

  • Actisite consists of tetracycline-containing fibers.
  • Each fiber has a diameter of 0.5 mm and contains 12.7 mg of tetracycline per 9 inches of fiber.

• Clinical Use:

  • The fibers are placed directly into periodontal pockets, where they release tetracycline over time, helping to reduce bacterial load and promote healing.

3. Arestin

• Composition:

  • Arestin contains minocycline, which is delivered as a biodegradable powder in a syringe.

• Clinical Use:

  • Arestin is indicated for the treatment of periodontal disease and is applied directly into periodontal pockets, where it provides localized antibiotic therapy.

4. Atridox

• Composition:

  • Atridox contains 10% doxycycline in a syringeable gel system that is biodegradable.

• Clinical Use:

  • The gel is injected into periodontal pockets, where it solidifies and releases doxycycline over time, aiding in the management of periodontal disease.

5. Dentamycin and Periocline

• Composition:

  • Both Dentamycin and Periocline contain 2% minocycline hydrochloride.

• Clinical Use:

  • These products are used similarly to other local delivery systems, providing localized antibiotic therapy to reduce bacterial infection in periodontal pockets.

6. Periochip

• Composition:

  • Periochip is a biodegradable chip that contains chlorhexidine.

• Clinical Use:

  • The chip is placed in the gingival crevice, where it releases chlorhexidine over time, providing antimicrobial action and helping to control periodontal disease.

Plaque Formation

Dental plaque is a biofilm that forms on the surfaces of teeth and is a key factor in the development of dental caries and periodontal disease. The process of plaque formation can be divided into three major phases:

1. Formation of Pellicle on the Tooth Surface

• Definition: The pellicle is a thin, acellular film that forms on the tooth surface shortly after cleaning.
• Composition: It is primarily composed of salivary glycoproteins and other proteins that are adsorbed onto the enamel surface.
• Function:
  • The pellicle serves as a protective barrier for the tooth surface.
  • It provides a substrate for bacterial adhesion, facilitating the subsequent stages of plaque formation.

2. Initial Adhesion & Attachment of Bacteria

• Mechanism:
  • Bacteria in the oral cavity begin to adhere to the pellicle-coated tooth surface.
  • This initial adhesion is mediated by specific interactions between bacterial adhesins (surface proteins) and the components of the pellicle.
• Key Bacterial Species:
  • Primary colonizers, such as Streptococcus sanguis and Actinomyces viscosus, are among the first to attach.
• Importance:
  • Successful adhesion is crucial for the establishment of plaque, as it allows for the accumulation of additional bacteria.

3. Colonization & Plaque Maturation

• Colonization:
  • Once initial bacteria have adhered, they proliferate and create a more complex community.
  • Secondary colonizers, including gram-negative anaerobic bacteria, begin to join the biofilm.
• Plaque Maturation:
  • As the plaque matures, it develops a three-dimensional structure, with different bacterial species occupying specific niches within the biofilm.
  • The matrix of extracellular polysaccharides and salivary glycoproteins becomes more pronounced, providing structural integrity to the plaque.
• Coaggregation:
  • Different bacterial species can adhere to one another through coaggregation, enhancing the complexity of the plaque community.

Composition of Plaque

• Matrix Composition:
  • Plaque is primarily composed of bacteria embedded in a matrix of salivary glycoproteins and extracellular polysaccharides.
• Implications for Removal:
  • The dense and cohesive nature of this matrix makes it difficult to remove plaque through simple rinsing or the use of sprays.
  • Effective plaque removal typically requires mechanical means, such as brushing and flossing, to disrupt the biofilm structure.

Periodontics: Dental specialty deals with the supporting and surrounding tissues of the teeth. 

1. Periodontium: tissues that invest and support teeth Includes Gingiva, Alveolar mucosa  Cementum, Periodontal ligament, Alveolar bone, Support bone

2. Periodontal disease: changes to periodontium beyond normal range of variation

a. Specific plaque hypothesis: specific microorganisms cause periodontal disease; mostly anaerobes. Three implicated: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteriodes forsythus

b. Contributing factors: often a combination of factors

i. Local: calculus (tarter, home for bacteria, ­ with age), traumatic occlusal forces, caries (root caries), overhangs and over-contoured restorations, open contacts with food impaction, missing/malaligned teeth

Invasion of biological width: from free gingival margin -> attached gingiva need ~ 3 mm.  If enter this area -> problems (e.g., resorption)

ii. Host factors: exacerbate periodontal problems; e.g., smoking/tobacco use, pregnancy and puberty (hormonal changes, ­ blood vessel permeability), stress, poor diet

iii.Medications: often -> tissue overgrowth; e.g., oral contraceptives, antidepressants, heart medicines, transplant anti-rejection drugs

iv.Systemic diseases: e.g., diabetes, immunosuppression

B. Gingivitis: inflammation of gingiva; ­ with age; generally reversible

C. Periodontitis: inflammation of supporting tissues of teeth, characterized by loss of attachment (PDL) and bone; generally irreversible

D.       Periodontal disease as risk factor for systemic diseases:

1.        Causes difficulty for diabetics to control blood sugar

2.        Pregnant women with periodontal disease ~ 7 times more likely to have premature and/or underweight baby

3.        Periodontal diseased patients may be at risk for heart disease

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.

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.

Anatomy and Histology of the Periodontium

Gingiva (normal clinical appearance): no muscles, no glands; keratinized

• Color: coral pink but does vary with individuals and races due to cutaneous pigmentation
• Papillary contour: pyramidal shape with one F and one L papilla and the col filling interproximal space to the contact area (col the starting place gingivitis)
• Marginal contour: knife-edged and scalloped
• Texture: stippled (orange-peel texture); blow air to dry out and see where stippling ends to see end of gingiva
• Consistency: firm and resilient (push against it and won’t move); bound to underlying bone
• Sulcus depth: 0-3mm
• Exudate: no exudates (blood, pus, water)

  Anatomic and histological structures

Gingival unit: includes periodontium above alveolar crest of bone

a. Alveolar mucosa: histology- non-keratinized, stratified, squamous epithelium, submucosa with glands, loose connective tissue with collagen and elastin, muscles.  No epithelial ridges, no stratum granulosum (flattened cells below keratin layer)

b. Mucogingival junction: clinical demarcation between alveolar mucosa and attached gingiva

c. Attached gingiva: histology- keratinized, stratified, squamous epithelium with epithelial ridges (basal cell layer, prickle cell layer, granular cell layer (stratum granulosum), keratin layer); no submucosa

• Dense connective tissue: predominantly collagen, bound to periosteum of bone by Sharpey fibers
• Reticular fibers between collagen fibers and are continuous with reticulin in blood vessels

d. Free gingival groove: demarcation between attached and free gingiva; denotes base of gingival sulcus in normal gingiva; not always seen

e. Free gingival margin: area from free gingival groove to epithelial attachment (up and over ® inside)

• Oral surface: stratified, squamous epithelium with epithelial ridges
• Tooth side surface (sulcular epithelium): non-keratinized, stratified, squamous epithelium with no epithelial ridges (basal cell and prickle cell layers)

f. Gingival sulcus: space bounded by tooth surface, sulcular epithelium, and junctional epithelium; 0-3mm depth; space between epithelium and tooth

g. Dento-gingival junction: combination of epithelial and fibrous attachment

• Junctional epithelium (epithelial attachment): attachment of epithelial cells by hemi-desmosomes and sticky substances (basal lamina- 800-1200 A, DAS-acid mucopolysaccharides, hyaluronic acid, chondroitin sulfate A, C, and B), to enamel, enamel and cementum, or cementum depending on stage of passive eruption.  Length ranges from 0.25-1.35mm.
• Fibrous attachment: attachment of collagen fibers (Sharpey’s fibers) into cementum just beneath epithelial attachment; ~ 1mm thick

h. Nerve fibers: myelinated and non-myelinated (for pain) in connective tissue.  Both free and specialized endings for pain, touch pressure, and temperature -> proprioception.  If dentures, rely on TMJ.

i.Mesh of terminal argyophilic fibers (stain silver), some extending into epithelium

ii  Meissner-type corpuscles: pressure sensitive sensory nerve encased in CT

iii.Krause-type corpuscles: temperature receptors

iv. Encapsulated spindles

i. Gingival fibers:

i.  Gingivodental group:

• Group I (A): from cementum to free gingival margin
• Group II (B): from cementum to attached gingiva
• Group III (C): from cementum over alveolar crest to periosteum on buccal and lingual plates

ii.  Circular (ligamentum circularis): encircles tooth in free gingiva

iii. Transeptal fibers: connects cementum of adjacent teeth, runs over interdental septum of alveolar bone.  Separates gingival unit from attachment apparatus.

Transeptal and Group III fibers the major defense against stuff getting into bone and ligament.

2.  Attachment apparatus: periodontium below alveolar crest of bone

Periodontal ligament: Sharpey’s fibers (collagen) connecting cementum to bone (bundle bone).  Few elastic and oxytalan fibers associated with blood vessels and embedded in cementum in cervical third of tooth.  Components divided as follows:

i. Alveolar crest fibers: from cementum just below CEJ apical to alveolar crest of bone

ii.Horizontal fibers: just apical to alveolar crest group, run at right angles to long axis of tooth from cementum horizontally to alveolar bone proper

iii.Oblique fibers: most numerous, from cementum run coronally to alveolar bone proper

iv. Apical fibers: radiate from cementum around apex of root apically to alveolar bone proper, form socket base

v. Interradicular fibers: found only between roots of multi-rooted teeth from cementum to alveolar bone proper

vi. Intermediate plexus: fibers which splice Sharpey’s fibers from bone and cementum

vii. Epithelial Rests of Malassez: cluster and individual epithelial cells close to cementum which are remnants of Hertwig’s epithelial root sheath; potential source of periodontal cysts.

viii. Nerve fibers: myelinated and non-myelinated; abundant supply of sensory free nerve endings capable of transmitting tactile pressure and pain sensation by trigeminal pathway and elongated spindle-like nerve fiber for proprioceptive impulses

Cementum: 45-50% inorganic; 50-55% organic (enamel is 97% inorganic; dentin 70% inorganic)

i.  Acellular cementum: no cementocytes; covers dentin (older) in coronal ½ to 2/3 of root, 16-60 mm thick

ii. Cellular cementum: cementocytes; covers dentin in apical ½ to 1/3 of root; also may cover acellular cementum areas in repair areas, 15-200 mm thick

iii. Precementum (cementoid): meshwork of irregularly arranged collagen in surface of cementum where formation starts

iv. Cemento-enamel junction (CEJ): 60-65% of time cementum overlaps enamel; 30% meet end-to-end; 5-10% space between

v. Cementum slower healing than bone or PDL.  If expose dentinotubules ® root sensitivity.

Alveolar bone: 65% inorganic, 35% organic

i. Alveolar bone proper (cribriform plate): lamina dura on x-ray; bundle bone receive Sharpey fibers from PDL

ii. Supporting bone: cancellous, trabecular (vascularized) and F and L plates of compact bone

Blood supply to periodontium

i. Alveolar blood vessels (inferior and superior)

A) Interalveolar: actually runs through bone then exits, main supply to alveolar bone and PDL

B) Supraperiosteal: just outside bone, to gingiva and alveolar bone

C) Dental (pulpal): to pulp and periapical area

D) Terminal vessels (supracrestal): anastomose of A and B above beneath the sulcular epithelium

E) PDL gets blood from: most from branches of interalveolar blood vessels from alveolar bone marrow spaces, supraperiosteal vessels when interalveolar vessels not present, pulpal (apical) vessels, supracrestal gingival vessels

ii. Lymphatic drainage: accompany blood vessels to regional lymph nodes (esp. submaxillary group)