Host Modulation

Dr. Elham Al-Qafaf

BDS, Mclindent, JDB(perio)
The balance between periodontal breakdown (i.e., disease) and periodontal stability (i.e., health)
Pathogenesis of periodontitis
 Introduction

• Host can be defined as the organism from which a parasite obtains its
nourishment or, in the transplantation of tissue, the individual who receives
the graft.

• Modulation is the alteration of function or status of something in response

to a stimulus.
• In diseases of the periodontium that are initiated by bacteria, the host is the
individual who harbors the pathogens, but it was not clear for many years
whether it was possible to modulate the host response to the pathogens
that led to breakdown of the attachment apparatus.
• The concept of host modulation is fairly new to the field of dentistry and
was introduced by Williams and Golub and colleagues

• In 1990, Williams concluded that “there are data from studies in animals and
human trials indicating that pharmacologic agents that modulate the host
responses believed to be involved in the pathogenesis of periodontal
destruction may be efficacious in slowing the progression of periodontitis.”
•
• In 1992, Golub and colleagues discussed host modulation with tetracyclines
and their chemically modified analogues
• Many clinicians previously thought that:
 Periodontal disease was an inevitable consequence of aging and was
uniformly distributed in the population

 Disease severity was directly correlated with plaque levels (i.e., the worse
the oral hygiene, the worse the periodontal disease)
• As a result of better epidemiologic data, It has been established that:
 periodontal disease is not a natural consequence of aging

 disease severity is not necessarily correlated with plaque levels

• The response of the periodontal tissues to plaque is different in patients:

o Patients with abundant plaque and calculus deposits that manifest as

gingivitis with shallow pocketing.
o In contrast, other patients, despite maintaining a high standard of plaque
control, succumb to advance/aggressive forms of periodontitis.
• The former group of patients is periodontal disease resistant, whereas the
latter group is periodontal disease susceptible.
• The mentioned observations led researchers to realize that the host
response to the bacterial challenge of subgingival plaque is the most
important determinant of disease severity, progression, and response to
therapy.
• Host modulation with chemotherapeutic agents or drugs is the latest
adjunctive therapeutic option for the management of periodontal diseases
• Host modulation therapy (HMT) is an emerging treatment concept in the
management of periodontitis.
• HMT is a means of treating the host side of the host–bacteria interaction.
• HMTs do not block normal defense mechanisms or inflammation;
instead, they:
ameliorate excessive or pathologically elevated inflammatory processes to
enhance the opportunities for wound healing and periodontal stability.

can be used to reduce excessive levels of enzymes, cytokines, and prostanoids

can also modulate osteoclast and osteoblast function (Fig.) .

 are the key to addressing many of the risk factors that have adverse effects
on the host response that are not easily managed (e.g., smoking, diabetes)
or cannot be changed (e.g., genetic susceptibility).

can be used to increase the levels of a person’s protective or

antiinflammatory mediators

provide benefits for other inflammatory disorders, such as arthritis,

cardiovascular disease, dermatologic conditions, diabetes, rheumatoid
arthritis, and osteoporosis.
 Systemically Administered Agents:

• A variety of drug classes have been evaluated as host modulation agents,

including NSAIDs, bisphosphonates, tetracyclines.
• Systemic nonsteroidal antiinflammatory drugs (e.g., ibuprofen) can cause
significant side effects with long-term use and are not advised.

• Antiosteoporotic agents (e.g., bisphosphonates) have a minimal effect on

periodontal bone loss but carry risks such as localized bone necrosis.
• Sub-antimicrobial–Dose Doxycycline:
• Sub-antimicrobial–dose doxycycline (SDD) is a 20-mg dose of doxycycline
(Periostat) (Fig.).
• SDD is the only systemically administered HMT approved, and it is indicated
as an adjunct to scaling and root planing (SRP) for treating periodontitis
• Clinical trials have demonstrated a clear benefit for SDD compared with SRP
alone
• It is taken twice daily for 3 months, up to a maximum of 9 months of
continuous dosing.
• The 20-mg dose exerts its therapeutic effect by enzyme, cytokine, and
osteoclast inhibition rather than by any antibiotic effect.

• It inhibits connective tissue breakdown by multiple non-antimicrobial

mechanisms.
• Mechanisms of Action
• In addition to its antibiotic properties, doxycycline has the ability to down-
regulate MMPs that can degrade extracellular matrix molecules, including
collagen.
• MMPs are secreted by the major cell types in the periodontal tissues (e.g.,
fibroblasts, keratinocytes, macrophages, PMNs, endothelial cells) and play a
key role in periodontitis.
• Excessive quantities of MMPs are released in inflamed periodontal tissues,
resulting in breakdown of the connective tissue matrix.
• The predominant MMPs in periodontitis are MMP-8 and MMP-9
• In addition to reductions in cytokine levels, SDD stimulates osteoblastic
activity and new bone formation by up-regulating collagen production (Fig).
  Inhibition of production of epithelial-derived
MMPs

 Downregulates expression of key inflammatory

cytokines including IL-1, IL-6, and TNF- as well as
PGE2
 Inhibition of MMPs
 Stimulates fibroblast collagen production

 Reduces osteoclast activity and bone resorption

 Blocks osteoclast MMPs
 Stimulates osteoblast activity and bone formation

Schematic drawing of a periodontal pocket shows the pleiotropic mechanisms by which

doxycycline inhibits connective tissue breakdown.
Potential adjunctive therapeutic approaches and points of intervention in the treatment
of periodontitis are shown in the context of the pathologic cascade of events
• Doxycycline at antibiotic doses (≥100 mg) versus SDD (20mg)
• Multiple clinical studies using sub-antimicrobial doses of doxycycline have
shown no difference in the composition or resistance level of the oral flora.
• These studies have shown no overgrowth of opportunistic pathogens, such
as Candida, in the oral cavity, gastrointestinal system, or genitourinary
system.
• There was no evidence of adverse events that could be attributed to
antimicrobial effects of treatment (well tolerated)
 Suggested Uses and Other Considerations
• Treatable Periodontal Conditions
• SDD is indicated in:
 the management of chronic periodontitis, and studies have focused on
chronic and aggressive forms of periodontitis
 patients with risk factors such as smoking, diabetes, osteoporosis or
osteopenia
 cases with genetic susceptibility
 cases that are refractory to treatment (the treatment response is limited)
• SDD is contraindicated in:
 any patient with a history of allergy or hypersensitivity to tetracyclines.
 pregnant or lactating women or to children younger than 12 years of age
because of the potential for discoloration of the developing
 gingivitis and periodontal abscess or when an antibiotic is indicated
• Sequencing Prescription With Periodontal Treatment
• SDD is an adjunct to mechanical periodontal therapy and should not be used
as a stand-alone treatment or monotherapy.
• SDD should be prescribed to coincide with the first round of SRP
• It is prescribed for 3 months, up to a maximum of 9 to 24 months of
continuous dosing depending on the patient’s risk.
• Modification of any risk factors, such as smoking, nutrition, stress,
contributing medications, faulty restorations, poor oral hygiene, and poor
diabetic control, should also be addressed at this time
• Combining With Periodontal Surgery or Local Delivery Systems
• Most clinical research has focused on using SDD as an adjunct to nonsurgical
periodontal treatment. However,
Studies have supported efficacy of SDD as an adjunct to periodontal
surgery
SDD treatment can also be combined with the local delivery of antibiotics
into the periodontal pocket through sustained-delivery systems.
• Monitoring Benefits of Therapy
Reductions in probing depths and gains in attachment that may be
observed after SRP plus SDD
Improving the quality of the periodontal tissues after treatment with SDD
with significant reductions in gingival indices and bleeding on probing
Radiograph
Host Modulation and Comprehensive Periodontal
Management
• SDD should be used as part of a comprehensive treatment strategy that
includes the following complementary treatment strategies:
• Patient education and motivation, including oral hygiene instruction; use of
powered toothbrushes, antiseptics in rinses, toothpastes, and irrigation
• Reduction of the bacterial burden by high-quality SRP
• Site-specific antibacterial treatment with local delivery systems or systemic
antimicrobial therapy in selected cases
• Host response modulation by HMT
• Risk factor modification and risk reduction strategies
• Periodontal surgery with or without HMT
 Locally Administered Agents

• Enamel Matrix Proteins, Growth Factors, and Bone Morphogenetic

Proteins
• Several local HMTs have been investigated for use as adjuncts to surgical
procedures to improve wound healing and stimulate regeneration of lost
bone, periodontal ligament, and cementum, restoring the complete
periodontal attachment apparatus.
• The locally applied HMTs approved by the FDA for adjunctive use during
surgery are enamel matrix proteins , recombinant human platelet-derived
growth factor-BB, and BMP-2
 References

• Newman and Carranz’s Clinical periodontology 13th ed