Host Modulation Therapy (HMT) is a treatment concept that reduces tissue destruction and stabilizes or even regenerates inflammatory tissue by modifying host response factors. It has been used for treating osteoporosis and arthritis for several decades; and its application in treating periodontal disease.

1. HOST
MODULATION
DR SHREEJA NAIR
Government Dental College Ahmedabad

2. The concept of host
modulation was first
introduced to dentistry by
Williams (1990) and Golub et
al (1987)
Host Modulation- modifying
or modulating destructive or
damaging aspects of the
inflammatory host response
that develops in the
periodontal tissues as a result
of the chronic challenge
presented by the subgingival
bacterial plaque (Philip M.
Preshaw Perio2000. 2008;
48:92–110)
• Reduction in tissue destruction and
stabilization or even regenerating the
periodontium by modifying or
downregulating destructive aspects of
the host response and upregulating
protective or regenerative responses.
• Purpose of host modulatory therapy is
to restore the balance of
proinflammatory destructive mediators
and anti-inflammatory mediators to
that seen in healthy individuals.

4. HISTORY Williams & colleagues (1985) - Beagle
dog model & human study- NSAIDs
block disease progression
Golub & co-workers (1992) - collagenase
enzymes - active component of
destructive processes in periodontitis.

5. CLASSIFICATION
Kenneth S. Kornman, 1999
1. Host Modulation 1: Blocking Direct Effectors of Bone and
Connective Tissue Destruction E.g. bisphosphonates, MMP
inhibitors
2. Host Modulation 2: Blocking Host Mechanisms That
Influence Clinical Outcomes E.g. NSAIDs, inhibitors of IL-1
and TNF
3. Host Modulation 3: Host Mechanisms That Influence
Bacterial Control E.g. agents that reduce levels of PGE2 , IL-
1,TNF
Reddy MS, Geurs NC, Gunsolley, 2003
1. Anti-proteinases : E.g. tetracyclines
2. Anti-inflammatory agents : E.g. NSAIDs
3. Bone sparing agents : E.g. Bisphosphonates
Salve GE, Lang NP, 2005
1. Modulation of Arachidonic acid metabolites E.g. NSAIDs
2. Modulation of MMPs E.g. TIMPs, Tetracyclines
3. Modulation of bone remodeling E.g. Bisphosphonates
4. Modulation of host cell receptors: E.g. blockade of receptors

6. VARIOUS
STRATEGIES
IN HOST
MODULATION
1. Regulation of Arachidonic Acid
(AA) metabolites
2. Regulation of MMPs
3. Regulation of Bone remodeling
4. Regulation Cytokines and their
receptors
5. Regulation of Nitric oxide
synthase (NOS) activity
6. Blocking of cell signaling
pathways
7. EMD, BMP AND GROWTH
FACTORS

7. Regulation of
Arachidonic
Acid (AA)
metabolites
THE VARIOUS NSAIDS THAT HAVE BEEN USED IN HMT
TOPICAL
SYSTEMIC
e.g. Ketoprofen
Acetyl salicylic acid
Flurbiprofen
Ibuprofen
Mefenamic acid
Disadvantage: rebound effect
ANTI INFLAMMATORY & PRO RESOLVING MOLECULES
• Lipoxins
• Aspirin triggered lipoxins
• Resolvins of the E series and D series
• Aspirin triggered epimeric forms from dha
• The neuroprotectins/protectins
• Maresins

8. Regulation
of MMPs
MMP INHIBITORS
ENDOGENOUS
• TIMP
• A2 MACROGLOBULIN
EXOGENOUS
• TETRACYCLINE AND ITS
ANALOUGE
• BISPHOSPHONATES

9. Regulation
of Bone
remodeling
BISPHOSPHONATES
• Bisphosphonates are analogues of pyrophosphate
which have potent inhibitory effects on bone
resorption.
• Interfere - osteoblast metabolism
-secretion of lysosomal enzymes
• Possesses anti-collagenase properties
• They bind to and accumulate in bone, remaining
there for months.
• Disadvantage:
– BONJ
– Inducing changes in white blood cell counts
– Alendronate, may cause oesophageal and stomach
ulcers

10. Regulation of
Cytokines and
their receptors
ANTICYTOKINE THERAPY
• Use of receptor antagonist
• Use of soluble receptors
• Use of neutralising antibodies [Anti cytokine
antibodies]
• Bind to receptor present in the target cell and
prevent the cytokine from binding to the target cell
• Eg IL-1R1a
• Are antagonist in function and lower the level of
cytokines
• Eg Anti TNF-α ab, Anti IL-6

11. Regulation
of Nitric
oxide
synthase
(NOS)
activity
• NO is short lived, highly reactive free radical
• Important role in immune homeostasis
• Involved in – lipid peroxidation, protein damage,
stimulation of cytokine release
• Exaggerated production of NO in several
inflammatory disorders
MODULATION OF NOS ACTIVITY
Agents used are
• Mercaptoalkylgaunides
• PARP (poly ADP ribose polymerase) inhibitors
• Grapeseed proanthocyanide extract

12. Blocking of
cell
signaling
pathways
• Inhibition of signal transduction can abolish
both the cell stimulation by various cytokines
and the production of pro- inflammatory
cytokines
• The 3 main pathways that can be targeted are
1. NF-ΚB pathway
2. MAPK pathway
3. OPG-RANKL pathway
Proteasome inhibitors
cytokine suppressive anti-
inflammatory drugs
(CSAIDs)
VX-702
SD 282

13. EMD, BMP
AND
GROWTH
FACTORS
• EMD initiates periodontal regeneration through
recruitment of cementoblasts to the root-surface and
stimulates these to form root-cementum, which will
thereafter secondarily lead to regeneration of
periodontal fibers and alveolar bone.
• GROWTH FACTORS & BMP
• GEM 21S
• rh PGDF-BB
ACTIONS
– stimulate fibroblasts proliferation and
extracellular matrix synthesis
– increase proliferation and differentiation of
endothelial cells
– stimulate proliferation of mesenchymal progenitor
cells differentiation of fibroblasts

14. COMPLEMENTARY
TREATMENT
STRATEGIES IN
PERIODONTITIS

15. FUTURE
TRENDS
• Tacrolimus [Immunomodulatory drugs]: Suppress expression of
TNF, IL-1 & IL-6
• Cimetidine [H2 antagonists]: Inhibits chemotaxis, phagocytosis,
superoxide production
• Clarithromycin & Midecamycin [Macrolides] : Suppress T cell
function (immunomodulatory)
• Calcium channel blockers : Decrease ratio of RANKL to OPG
• Curcumins & chemically modified curcumins :
– Contain PEZBIN
– Inhibit MMP action
• Semisynthetic glycosaminoglycan ether (SAGE):
– reduce the impact of advanced glycation end products (AGEs)
– reduce the proinflammatory mediators of disease like
cytokines