Periodontitis is a complex infection initiated by bacteria –tissue destruction. Host: the organism from which a parasite obtains its nourishment/ an individual who receives a graft Modulation: the alteration of function or status of something in response to a stimulus or an altered physical or chemical environment

1. GUIDED BY: PRESENTED BY:
DR DIVYA JAGGI DR ANKITA DADWAL
HOST MODULATION THERAPY

2. CONTENTS
 INTRODUCTION
 PATHOGENESIS OF PERIODONTITIS AND HOST
RESPONSE
 HOST MODULATORY THERAPY
 HOST MODULATING AGENTS
 LOCALLYADMINISTERED HOST MODULATION
THERAPY
 NEW AGENTS IN HOST MODULATION
 CONCLUSION
 REFRENCES
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3. INTRODUCTION
 Periodontitis is a complex infection initiated by
bacteria –tissue destruction.
Host: the organism from which a
parasite obtains its nourishment/ an
individual who receives a graft.
Modulation: the alteration of function or
status of something in response to a
stimulus or an altered physical or
chemical environment2/38

4. PATHOGENESIS OF PERIODONTITIS
AND HOST RESPONSE
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5. HOST MODULATION THERAPY
Treatment concept that aims to reduce the 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.
- 1st introduced in dentistry – William’s (1990) and Golub
et al (1992)
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6. RATIONALE
To restore the balance of pro-inflammatory and anti-inflammatory
mediators
As Adjunctive treatment options
To decrease pt. susceptibility
To aid in risk assessment & risk reduction strategy
To facilitate regeneration
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7. CLASSIFICATION
• NSAIDS
• SDD
• Bisphosphonates
• Modulation of host cell receptors
• Modulation of NOS activity
Systemically
Administered
Agents
• NSAIDS
• Enamel Matrix Proteins,
• Growth Factors and BMP’S
Locally
Administered
Agents
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8. HOST MODULATING AGENTS
 INHIBITION OF ARACHADONIC ACID
METABOLITE:
A) COX-1 INHIBITOR: indomethacin
B) cox-2 INHIBITOR : Rofecoxi
C) COX and LOX inhibitors: Triclosan, topical ketoprofen
D) LOX INHIBITOR: lipoxins
 MODULATION OF MMPs:
A) TETRACYCLINE
B) CMT
C) SDD
D) BISPHOSPHONATES7/38

9.  MODULATION OF BONE REMODELLING:
A) Conventional therapy
B) Tumor necrosis factor – alpha
C) Anticytokines drugs
D) Antiresorptive therapies
 hormonal replacement therapy
 bisphosphonates
 disruptive of the RANKL/RANK/ OPG
 vitamin D
 statins
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10.  REGULATION OF IMMUNE AND
INFLAMMATORY RESPONSE:
A) Supressing proinflammatory cytokines: IL1 and
TNF alpha antagonist
B) modulation of nitric oxide activity
 OTHER AGENTS:
A) probiotics
B) nutrients
 LOCALLYADMINISTERED HMT
 NEW EMERGING HOSTS:
Azithromycin
paratyroid
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11. MODULATION OF ARACHIDONIC
ACID METABOLITE
NSAIDS
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12.  NSAIDs such as indomethacin (williams RC jp 1987),
flurbiprofen (jeffcoat MK JP 1989), and naproxen(Howell TH
1993) administered daily for up to 3 years, significantly slowed
the rate of alveolar bone loss compared with placebo.
 DISADVANTAGES OF NSAIDS AS HMT:
 gastrointestinal problems,
 hemorrhage (from decreased platelet aggregation),
 and renal and hepatic impairment
 REBOUND EFFECT
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13. TOPICAL NSAIDS IN PERIODONTICS
 NSAIDS : KETOROLAC TRIMETHAMINE RINSE
S- KETOPROFEN DENTRIFICE
 chronic periodontitis who received topical ketorolac mouthrinse
reported that gingival crevicular fluid (GCF) levels of PGE2 were
reduced by approximately half over 6 months and that bone loss
was halted ( Jeffcoat MK et al:. J Periodontol 1995).
 Ketoprofene block both CO and LO pathways.
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14. LIPOXINS, RESOLVINS, PROTECTINS
 Biosynthesized during the resolution phase of acute
inflammation.
 Pouliot et al (1999), lipoxins blocked IL1 beta
secretion from PMNs.
 LIPOXIN A4
 LIPOXIN B4
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15. INHIBITION OF MMPs
MMP inhibitor
endogenous
TIMP
Alpha
macroglobulins
exogenous
Tetracyclines
Bisphosphonates
CMT
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16. TETRACYCLINES
Mediated by cellular
mechanisms
• decrease cytokines,
inducible nitric oxide
synthase,
phospholipase A2,
prostaglandin
synthase
• Effects on protein
kinase C, calmodulin
Mediated by
extracellular
mechanisms
• Direct inhibition of active
MMPs
• Inhibition of oxidative
activation of pro-MMPs
• Tetracyclines disrupt
activation by promoting
excessive proteolysis of pro-
MMPs into enzymatically-
inactive fragments
• Inhibition of MMPs protects
α1-proteinase inhibitor, thus
indirectly decrease serine
proteinase (elastase)
activity
Mediated by pro-
anabolic effects
• Tetracyclines
increase collagen
production
• Tetracyclines
increase osteoblast
activity and bone
formation

17. CHEMICALY MODIFIED
TETRACYCLINES
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18. ADVANTAGES OVER
TETRACYCLINES
 No development of bacterial resistance that is found with the
traditional tetracyclines.
 Less incidence of adverse effects such as GIT disturbances,
superinfection.
 It has anticollagenase property that is very important to inhibit
the periodontal tissue destruction.
 Substantivity of the drug, high concentration in GCF.
 Rifkin et al reported that CMT could also inhibit PTH induced
bone resorption.
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19. SUBANTI MICROBIAL DOSE
DOXYCYCLINE
 At present SDD (Periostat) is the only systemically administered
HMT specifically indicated for the treatment of chronic
periodontitis that is approved by the US Food and Drug
Administration (FDA) and accepted by the American Dental
Association (ADA).
 Studies conducted by Preshaw et al in J
Periodontol 2008 utilizing this same modified-release SDD
versus placebo with periodontitis as an adjunct to SRP resulted
in significantly greater clinical benefits than SRP alone in the
treatment of periodontitis.
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20.  Golub et al 1985 reported that a 2-week regimen of SDD reduced
collagenase in GCF and in the adjacent gingival tissues surgically
excised for therapeutic purposes.
 He found using SDD therapy adjunctive to routine scaling and
prophylaxis cause continued reductions in the excessive levels of
collagenase in the GCF after 1 month of treatment.
 After cessation of SDD administration, however, there was a rapid
rebound of collagenase activity , suggesting that a 1-month
treatment regimen with this host modulation agent was insufficient
to produce a long-term benefit(Ashley RA 1999)
 In contrast, during the same study, a 3-month regimen produced a
prolonged drug effect without a rebound in collagenase levels to
baseline during the no-treatment phase of the study.
these reductions in collagenase levels were gains in the relative
attachment levels in the SDD group( Ashley RA 1999)
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21. Sequencing Prescription With Periodontal
Treatment
 Not used as monotherapy, Used as an adjunct to SRP. To be
prescribed to coincide with the first episode of SRP.
 Taken as 20mg twice daily for 3 months and up to a maximum of 9
months of continuous dosing.
 After initial periodontal treatment, the patient is enrolled into an
intensive maintanence program. (re evaluation of probing depths,
reinforcement of oral hygiene, SRP, remotivation of the patient).
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22. INDICATIONS
Motivated
patients
Chronic and
aggressive
periodontitis
patients treated
non surgically.
(Caton J et al,
2000,Preshaw
et al 2005)
Patients
traditionally
considered
resistant to
periodontal
treatment
(smokers).
Cases
considered
refractory to
treatment and
those with
risk factors
like diabetes
and smoking.
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23. CONTRAINDICATIONS
History of
allergy or
hypersensitivity
Pregnant and
lactating
women or
children less
than 12 yrs of
age
conditions like
gingivitis and
periodontal
abscess or when
an antibiotic
regimen is
necessary
May reduce the
effectiveness of
oral
contraceptives
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24. BISPHOSPHONATES
 The bisphosphonates are bone-seeking agents . inhibit bone
resorption by disrupting osteoclast activity.
 interfere with osteoclastic metabolism and secretion of
lysosomal enzymes (Weinreb M et al J Periodontal 1994)
possess anticollagenase properties (Nakaya H et al J
Periodontol 2000)
 treatment with the bisphosphonate significantly increased bone
density compared with placebo ( Reddy MS et al J
Periodontol 1995)
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25. MECHANISM OF ACTION
TISSUE LEVEL
• ↓ bone turnover
due to ↓ bone
resorption
• ↓ number of new
bone
• multicellular units
• Net positive
whole
• body bone
balance
CELLULAR
LEVEL
• ↓ osteoclast recruitment
• ↑ osteoclast apoptosis
• ↓ osteoclast adhesion
• ↓ depth of resorption
site
• ↓ release of cytokines
by
• macrophages
• ↑ osteoblast
differentiation and
number
MOLECULAR LEVEL
• ↓ post-translational
prenylation
• of GTP-binding
proteins
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26. DISADVANTAGES OF BISPHOSPHONATES
 inhibiting bone calcification
 inducing changes in white blood cell counts.
 avascular necrosis of the jaws following bisphosphonate
therapy, with the resultant risk of bone necrosis following
dental extractions (Carter G, Goss AN Med J Aust 2005)
 As with NSAIDs, at present there are no bisphosphonate drugs
that are approved and indicated for treatment of periodontal
diseases
 BRONJ
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27. MODULATION OF BONE REMODELLING
 TUMOR NECROSIS FACTOR – ALPHA :
 indirect and direct bone resorption.
 TNF alpha antagonist drugs –
 Infliximab
 Golimumab
 centrolizumab
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28. ANTICYTOKINES DRUGS
IL-1 Receptor
antagonist
Anakinra
AMG714
Monoclonal
Antibody to
TNF alpha
Infliximab
Adalimumab
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29. DISRUPTIVE RANK/RANKL/OPG
 Expression of the RANKL gene in osteoblasts/stromal cells is
enhanced by
1. Vitamin D3
2. PTH
3. IL-1, IL-6, IL- 17
4. TNF-α
5. BMP-2
6. PGE2
RANKL inhibitor : Denosumab
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30. CATHEPSIN K INHIBITOR
 It has role in degradation of type I and II collagen. So it can be
viewd as a target for modulation bone resorption.
 VIT D has anti inflammatory and immunomodulatory
properties.
 STATINS - SIMVASTATIN
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31. NO SYNTHETASE INHIBITOR
 L-NG-monomethyl arginine
 L-arginie methyl ester
 Mercapto ethyle guanidine:
 blocks inducible NOS, scavenges peroxy nitrite &
 inhibits COX production.
 N-iminoethyl-L-lysine:
 reduce MMP activity in cartilage
 reduce production of IL-1β
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32. ANTIOXIDANT
TYPES EXAMPLES
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 PREVENTIVE
ANTIOXIDANTS
 RADICAL
SCAVENGING
ANTIOXIDANTS
 DNA REPAIR
ENZYMES
 CATALASE
 GPX
 VIT A
 VIT E
 VIT C
 PROTEASES
 TRANSFERASES
 LIPASES

33. LOCALLY ADMINISTERD AGENTS
 NONSTEROIDAL ANTIINFLAMMATORY DRUGS
 ENAMEL MATRIX PROTEINS
 BONE MORPHOGENETIC PROTEINS (BMP-2, BMP-7),
 GROWTH FACTORS (PLATELET-DERIVED
GROWTH FACTOR,
 INSULIN LIKE GROWTH FACTOR.
 TETRACYCLINES
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34.  The initial local host modulatory agent approved by the
FDA for adjunctive use during surgery to assist with
clinical attachment gain and wound healing was
EMDOGAIN
 PLATELET-DERIVED GROWTH FACTOR combined
with a resorbable synthetic bone matrix (GEM 21S) to
assist in regenerative procedures , wound healing,
particularly in patients with diabetes
 rhBMP-2 (INFUSE) soaked on to an absorbable collagen
sponge to assist with ridge and sinus augmentation and
healing of fractures by the orthopedic community
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35. PROBIOTICS
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 A preparation or a product containing viabale, defined
microorganism in sufficient number, which can alter
the microflora in a compartment of the host.
 Can be becteria , yeast or moulds.
 Eg: yougurt, cheese, lozenges

36. NEW AGENTS FOR HOST
MODULATION
AZITHROMYCIN, a type of macrolide antibiotic.
- Suppress periodontopathogens
- Anti inflammatory activity
- Healing through persistence at low levels in macrophages and
fibroblasts
- Suppress the production of pro-inflammatory cytokines and
increase the production of anti inflammatory cytokines.
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37. PARATHYROID HORMONE
 TERIPARATIDE, a biosynthetic human parathyroid hormone, is
an anabolic agent.
 Fibroblast growth factor 2, production is upregulated.
 It regulates the proliferation and differentiation of osteoblast
progenitors
 Reduce sclerostin, a potent inhibtor of bone formation, could
account for part of the anabolic response to PTH.
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38. CONCLUSION
 Plaque bacteria are essential for periodontitis to occur but are
insufficient by themselves to cause the disease. For periodontitis
to develop, a susceptible host is also required.
 As we know the majority of periodontal destruction is caused by
host immuno-inflammatory response, various advanced
treatment modalities have been introduced in the recent years
including HMT.
 Though various agents are there to modulate host response,
only few have shown successful result in humans.
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39. REFRENCES
 Carranza 12th edition
 Newman M, Takei H, Klokkevold P, Carranza F. “Clinical
Periodontology”,10,11th, Edition. Saunders, Elsevier. Preshaw PM. Host
response modulation in periodontics. Periodontol 2000. 2008;48:92-
110. Review.
 D W Paquette & R C. Williams. Modulation of host inflammatory
mediators as a treatment strategy for periodontal diseases.
 Minkle Gulati, Vishal Anand, Vivek Govila, and Nikil Jain. Host
modulation therapy: An indispensable part of perioceutics. JIndian Soc
Periodontol. 2014 MayJun;18(3): 282–28838/38

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