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HMT for Periodontium Host modulatory therapy is a treatment concept that aims to reduce tissue

destruction and stabilize or even regenerate the periodontium by modifying or

down regulating destructive aspects of the host response and up regulating

protective or regenerative responses

Periodontopathic microorganisms disease initiation and progression

microbial challenge consisting of antigens, lipopolysaccharides (LPS) and other

virulence factors Activation of host responces

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Activation of host has both protective and destructive aspects. Protective aspects --recruitment of neutrophils, --production of protective antibodies, --release of various anti-inflammatory cytokines TGF- β, IL-4, IL-10 and IL-12 destructive aspects --pro-inflammatory cytokines, (e.g. IL-1, IL-6, TNF- α), --Matrix Metalloproteinases (proteases) --prostaglandin E2 (PGE2) --promote extracellular matrix destruction stimulate bone resorption.

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Host Modulatory Agents Various HMT have been developed or proposed to block pathways responsible for periodontal tissue breakdown A. Inhibition of Matrix metalloproteinases (MMPs): Through Chemically Modified Tetracyclines (CMTs) B. Inhibition of Arachidonic acid metabolites Through NSAIDs

a. COX – 1 inhibitors: Indomethacin, Naproxen, Flurbiprofen

b. COX – 2 inhibitors: Rofecoxib

c. COX and LOX inhibitors: Triclosan, Topical Ketoprofen

d. LOX inhibitors: Lipoxins

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C. Modulation of bone metabolism:

a. Bisphosphonates

b. Hormone replacement therapy (HRT)

c. Calcium supplementation

D. Regulation of immune and inflammatory responses:

a. Suppressing proinflammatory cytokines

(IL-1, TNF-α receptor antagonists)

b. Nitric Oxide inhibition

c. Generation of protective antibodies through vaccines

d. Infusion/supplementary anti-inflammatory cytokines IL-4 and IL-10

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--The use of HMT as an adjunct may be particularly useful in susceptible, high

risk patients (e.g. smoking, diabetes, genetic predisposition) FDA has recently

approved subantimicrobial dose doxycycline (Periostat™ 20 mg bid) for

systemic administration as an adjunct to scaling and root planning in the

treatment of chronic periodontitis.

--Main effect of HMT inhibits MMPs