Periodontics Host Modulation Therapy Question And Answers

Host Modulation Therapy Question And Answers

Question 1. What is the rationale for host modulatory therapy?
Answer:

• Periodontal disease is initiated by bacterial colonization of the tooth surface that triggers an immunoinflammatory response in the adjacent host tissues.
• Although bacterial pathogens are required to initiate the disease process, it has become evident that their presence alone is not sufficient to cause the degree of tissue destruction that occurs in periodontitis.
• The bacteria initiates disease by activating host mechanisms that then destroy the supporting structures of the periodontium.

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• In health, the gingival tissue is provided with a normally robust inflammatory/immune response.
• As periodontal tissues are constantly exposed to microbial antigens, this inflammatory cell response ensures the maintenance of tissue homeostasis.
• Periodontal disease occurs as a result of an imbalance between invading periodontopathogens and the host response.
• Traditional techniques of periodontal therapy have involved the removal of offending pathogens in order to bring about the balance between the microbial and host response.
• It is, of course, well documented that removal of the bacterial challenge will sufficiently reduce the flow of destructive mediators such that tissue destruction will not occur.
• The removal of existing bacterial accumulations and regular bacterial control should be considered the most reliable prevention and therapeutic approach to the management of periodontitis.
• As a therapeutic procedure, the process of removal of microorganisms suffers from the following limitations.

1. Plaque control is a continuous process that requires a sustained effort from the patient that is sometimes difficult to perform over a long period.
2. The bacteria in plaque have demonstrated an ability to colonize in areas other than the gingival crevice, such as the soft palate, tonsil, and dorsum of the tongue. These relatively inaccessible areas increase the difficulty of maintaining the plaque bacteria within disease limits.
3. Periodontopathogens have also demonstrated the ability to invade the gingival tissues. These bacteria are very difficult to get rid of with conventional therapeutic procedures.

• In recent years, investigators have used another approach to treat periodontal disease. Instead of trying to eliminate the disease-causing organisms, efforts have been made to minimize the damage that has been caused by altering/modifying the host response.
• The entire gamut of procedures that modify host response in an effort to minimize tissue destruction in periodontal disease has been classified under what has been termed ‘Host modulation therapy’.

Question 2. Discuss the agents used in host modulation therapy.
Answer:

Inflammatory Mediators

• Inflammatory mediators are required for the process of inflammation which is of course critical for defense mechanisms and tissue repair.
• Proinflammatory mediators such as IL-1. IL-6 and IL-8 are important for the maintenance of this inflammatory response.
• In periodontal disease, however, there is a prolonged and excessive liberation of these proinflammatory cytokines.
• This results in activation of the MMPs/an unresolved excessive inflammatory response and osteoclast activation, all of which lead to soft and hard tissue destruction.
• MMPs such as MMP-8 and -9 have been closely associated with tissue destruction in periodontal disease and several authors have documented increased MMP levels in gingival crevicular fluid.
• Host modulation therapies have so far been directed against them.

1. Proinflammatory cytokines and prostaglandins such as PGE2
2. MMPs
3. Osteoclast activators.

These classes of host-modulating agents have been used so far in the treatment of periodontal disease.

1. NSAIDs
2. Bisphosphonates
3. MMP inhibitors—tetracycline in their natural and modified forms.

Question 3. Describe the use of NSAIDs in host modulation.
Answer:

• NSAIDs were one of the earliest agents used in host-modulating periodontal therapy by virtue of their inhibiting effect on the cyclooxygenase pathway.
• These agents suppress the conversion of arachidonic acid to prostaglandins. PGE2 is thought to be closely associated with both the inflammatory process and the bone loss observed in periodontal disease.
• The rationale of using NSAID was to down-regulate PGE2 synthesis, thereby inhibiting the bone loss observed in periodontal disease.
• Flurbiprofen has been used for this purpose and there is some evidence of its possible influence on regulating periodontal destruction.
• The use of NSAIDs is not without its adverse effects. Other than its well-documented effect on the gastrointestinal tract, ototoxicity and nephrotoxicity, and other idiosyncratic reaction, its ability to regulate the inflammatory process has also been questioned.
• As a result, NSAIDs are not a popular choice for host-modulating therapy today.

Question 4. Write briefly about bisphosphonates as host-modulating agent.
Answer:

• Bisphosphonates were introduced in medicine as bone-sparing agents, as a result of their ability to down-regulate osteoclast activation.
• As bone loss is a cardinal feature of periodontitis, the use of bisphosphonates seems to be a viable option.
• Bisphosphonates are shown the ability to inhibit osteoclastogenesis, affect osteoclast differentiation and regulate their resorption of mineralized tissues.
• Bisphosphonates have been classified into various generations depending on their chemical structure and it has been postulated that the second generation bisphosphonates exhibit comparatively fewer adverse effcts when compared to the other generations.
• Bisphosphonates have been widely used in the treatment of rheumatoid arthritis, but their use in periodontal disease has been limited to experimental stages.
• The potential for complications such as avascular necrosis and malignancies has limited their mode wide spread use.

Anti MMPS

By far the most effective and well-documented host modulating agents are tetracycline and their subsequent modifiations. Properties of tetracyclines that make them suitable candidates for host modification

• In addition to their antibacterial effect, tetracyclines exhibit strong anti-MMP properties. As MMPs, especially MMP -8 and -9 are closely associated with tissue destruction in periodontitis, tetracyclines are capable of regulating the destructive process.
• Tetracyclines are capable of inhibiting the production of reactive oxygen species (ROS). Oxidant stress is thought to be an important component of the destructive processes that occur in periodontal disease. Free radical scavenging may therefore help retard/arrest disease progression.
• Tetracyclines have shown the ability to interfere with the monocyte/macrophage-induced osteoclast activation, thereby providing the beneficial effect on excessive bone loss.

The use of tetracyclines as an antimicrobial agent in the treatment of periodontal disease is well documented and has been discussed elsewhere in this book. Long-term use of tetracycline is not without its limitations as:

• It can lead to bacterial resistance
• Superadded infection by fungi such as candida
• Systemic side effects are normally associated with their long-term use.
• Golub and co-workers demonstrated that tetracyclines retained their anti-collagenase effect even at concentrations much lower than that required for their antibacterial effect.
• This finding lead to the use of tetracyclines at lower than their normal antimicrobial concentration.

Question 5. Discuss the role of subantimicrobial doxycycline (SDD) as host modulating agent.
Answer:

• Doxycycline has demonstrated perhaps the most potent anti-collagenase effect amongst the various tetracyclines available today.
• A sub-antimicrobial dose (SDD) of doxycycline has been devised which retains its anti-collagenase effect while demonstrating no antimicrobial properties.
• The commercially available 20 mg doxycycline (Periostat) has been used in the treatment of chronic periodontitis.
• Several studies have documented significantly better results when SDD has been used in conjunction with root planning when compared to root planning (SRP) alone.
• Investigators have used SDD for a variable period 1–3 months usually with a twice-daily dosage.
• A cyclic regimen SDD has also been described, where doxycycline has been administered for 3 months and then stopped for a similar period and continued again for three months.
• Although this formulation has shown signifiant clinical benefits, the following limitations have been observed:

1. Bacterial resistance has been observed in spite of its limited antibacterial activity.
2. Stray incidence of candidal infections have also been reported.

Question 6. Write a note on chemically modified tetracycline (CMT) in host modulation.
Answer:

• In order to circumvent the adverse reactions observed with SDD, Golub et al have further modified the tetracycline molecule by removing the NH2 group attached to the C4 carbon atom.
• In the absence of this side chain, tetracycline exhibits no antibacterial effect as it is unable to combine with the bacterial ribosome.
• The anti-collagenase effect and the anti-ROS effects are retained as they are mediated by different parts of the same molecule.
• These tetracyclines have been termed chemically modified tetracycline (CMT) and have shown promise as host-modulating agents in experimental studies. Results of human clinical trials are however yet to be obtained.
• The host modulating agents described above have all exhibited the considerable ability to down-regulate the inflammatory mediators or MMPs.
• These agents are limited by their negligible effect on the inflammatory cell infiltrate that actually perpetuates the disease process.
• Newer host-modulating agents have been recently identified, with the ability to down-regulate inflammatory cell infiltrate or modify the inflammatory cells to favor repair rather than destruction.
• These newer agents are lipoxins and resolvins, both of which are known to prevent or regulate excessive neutrophil activity.
• These newer agents are yet to be studied with long-term clinical trials and today are still considered agents with most promising effects.

Conclusion

• The importance of plaque control measures in the treatment of periodontal disease cannot
  be ignored.
• It is also true, however, that disease activity is dependent on the host response and therefore modifying this response may achieve the goal of arresting disease progression.
• The use of host modulatory agents holds a lot of promise and in the event of well-documented evidence emerging that supports its use may hold the therapy for the future.