Critical issues in periodontal research

Khushbu Mishra

• Guided by:-

Dr. Veena A Patil

Introduction

• In common with all areas of medicine, periodontal research is

increasing at an exponential rate.

• Huge numbers of papers are published each year that address

all aspects of periodontology, with their primary aim being to

improve the clinical management of periodontitis.

• "The clinical discipline we call periodontology has come a

long way. Concepts and procedures for the treatment of

periodontal diseases are scientifically based, well-defined, and

generally adopted and applied by clinicians. Rational measures

to prevent these diseases are available and widely practiced in

industrialized societies. The goal of virtually eliminating

periodontal diseases as a public health problem seems not only

feasible but probable for the large majority in most

populations" (Loe, 1993).

• In spite of the tremendous progress that has been made, many

unresolved problems remain.

Epidemiology/prevalence

Marshall-Day et al. 1955

• It was widely accepted that once periodontitis was initiated, if

left untreated it progressed inexorably in a continuous and

linear manner until tooth loss occurred (Greene, 1963).

• The picture was one of almost universal prevalence in adults.

Brown and Loe 1993

• Thus, these studies demonstrated a prevalence much lower

than expected, with severe periodontitis observed in a very

small proportion of the population.

• Individuals with low plaque and calculus levels have little or

no periodontitis, compared with individuals with chronically

high levels of plaque and calculus who have much higher

levels of more severe periodontitis.

• Study was done by Baelum et al. (1986) on villagers in the

Zanzibar and Pemba Islands region of Tanzania, who have had

little or no access to dental care and who manifested extremely

high levels of plaque and calculus.

• Fewer than 10% of individuals had attachment loss exceeding

6 mm, and the mean number of teeth present in the oldest

members of the study population was 23.9.

• Is the prevalence of periodontitis changing?

• Severity is less than that previously observed, but whether

prevalence is decreasing remains unresolved.

• Clearly, the data gathered in the United States and elsewhere in

recent years do not support a universal prevalence in adult

populations. (Page 1989)

• It is abundantly clear that a relatively small proportions of

population studied has been susceptible to severe periodontitis.

• How to determine the identity and characteristics of the severe

periodontitis group?

• There is evidence that severe periodontitis is much higher in

American Blacks, especially older males, than in Caucasians

(Hughes et al., 1982),

• and that individuals in the lower socioeconomic and

educational groups are significantly at greater risk for severe

periodontitis.

• Studies aimed at identification of high-risk groups and

subpopulations are badly needed.

• To determine the validity of the concept that good oral hygiene

equates to periodontal health while poor or no oral hygiene

results in a high prevalence of severe periodontitis ….

•Microbiology/etiology

Microbiology/Etiology

• Whether a dozen or more microbial species are in fact

involved in a meaningful way in the etiology of human

periodontitis?

• There may be only one or, at most, two species essential for

the initiation of periodontitis, while the other species may be

innocent bystanders, or may participate in propagation of

lesions once initiated.

• Periodontitis could be a consequence of a sequential infection,

as suggested by Williams et al. (1985).

• The multiple species of bacteria that have been implicated in

the etiology of periodontitis may share a common

characteristic or factor that is the immediate cause of the

disease.

• whether periodontal infections are a consequence of

overgrowth of commensal periodontal microflora or

exogenous infections?

• Putative periodontal pathogens can be found at periodontally

normal sites in patients with periodontitis

(Socransky et al., 1991)

• and at sites in periodontally normal individuals

(Dahlen et al., 1989; McNabb et al., 1992).

• These observations support the idea that, with sufficiently

sensitive techniques, pathogenic species can be found

commonly in periodontally normal individuals.

• Actinobacillus and P. gingivalis are transmitted among family

members

(DiRienzo and Slots, 1990;

Alaluusua et al., 1993;

Petit et al., 1993a,b),

• and between spouses (Saarela et al., 1993;

van Steenbergen et al., 1993).

• A. actinomycetemcomitans from the family pet dog to a child.

(Preus and Olson, 1988).

• Question of the relationship between the presence of a

"pathogenic" flora and disease status.

• Haffajee and Socransky (1994) have shown that thresholds

exist below which periodontal sites, even though colonized by

a given pathogen, are disease inactive, but above which

disease activity is observed.

• The threshold for disease activity for P. gingivalis appears to

be about 5 x 10⁵, and that for A. actinomycetemcomitans just

over 10⁴ bacterial counts.

• various strains of periodontopathic bacteria such as P.

gingivalis differ greatly with regard to virulence and

pathogenicity

(Marsh et al., 1989; Neiders et al., 1989;

Shah et al., 1989; Smalley et al.1989;

Socransky and Haffajee, 1991, 1992).

• The role that environment and ecology play in bacterial gene

expression, genetic change, and virulence….

• There is evidence that local environmental factors may be

major determinants of virulence. For example,

• the concentration of iron is a major determinant of the

production of certain cell-envelope proteins that may be

important virulence factors (McKee et al., 1986; Barua et al.,

1990; Bramanti et al., 1993).

• Bleeding pocket

• temperature, pH,

• the concentration of ions such as calcium and magnesium

• Interactions among and between species are also known to

occur.

Pathogenesis

• Lavine et al. (1976) reported that peripheral blood neutrophils

harvested from teenagers with localized juvenile periodontitis

(LJP) were abnormal in that their response to chemo-

attractants in vitro was significantly less than that of cells from

normal individuals.

• This abnormality was considered to predispose individuals

having it to early-onset severe forms of periodontitis.

• The defect appeared to be genetically based, and to account

for the familial pattern of LJP cases. This contention however

remains to be proved.

• An additional advancement in the area of pathogenesis was the

demonstration by Mouton C, Hammond PG et al. that some

patients with periodontitis mount a humoral immune response

to the antigens of their infecting pathogens.

• The role these antibodies may play in the pathogenesis of the

disease process remains to be clarified.

Mechanism of tissue destruction

Heath et al. 1987; Meikel et al. 1989; Birkedal-Hansen et al. 1993

Page 1991; Birkedal-Hansen 1993

• Over time, we will undoubtedly develop ways to control gene

activation, and thereby block destruction of the periodontal

tissues.

Issues related to diagnosis

• Our inability to make the distinction between diseased and

healthy pockets.

• Identification of risk indicators and factors is of enormous

importance in diagnosis and treatment planning of

periodontitis patients.

In general, the higher the category of risk, the more aggressive

the treatment needed.

Issues relating to therapy

• First, the approaches we have relied on most for regeneration

of periodontal tissues are various grafting procedures and

guided-tissue regeneration. These have been moderately

successful.

• These procedures usually fail at those sites where we do not

have other treatments that do succeed, and are successful in

those cases where other treatments are available (Page, 1993).

• A second critical issue is our lack of understanding of why

some patients fail to respond favorably to any form of

periodontal therapy..

• At the present time, we are unable to identify them prior to

treatment, and we have no understanding of the reasons they

fail to respond favorably.

• Do periodontitis patients produce antibodies to their infecting

bacteria?

• and if not, why?

• If so, are they protective, and if not, why?

• Studies have shown that roughly half of young adults with

severe periodontitis fail to produce serum antibodies to the

infecting bacteria (Chen et al., 1991; Whitney et al., 1992).

• In those who do, the antibodies are not effective in

opsonization and in enhancing phagocytosis and killing of

bacteria (Chen et al., 1991; Sjbstrom et al., 1992).

• Treatment by scaling and root planing is known to result in

bacteremia. It was suspected that such treatment could be a

form of vaccination.

• Idea was tested and demonstrated that treatment activates an

immune response in those individuals who were previously

seronegative, and the induced antibodies are more effective in

enhancing phagocytosis and killing than those produced

during the course of spontaneous infection (Chen et al., 1991)

• A Macaca fascicularis nonhuman primate model to test the

idea.

• Experimental periodontitis was induced in monkeys and

demonstrated that immunization using a vaccine containing a

killed periodontal pathogen could arrest destruction of alveolar

bone (Persson et al., 1994).

• To achieve an understanding of the role that the host defense

mechanisms, especially the immune response, play in

periodontitis, and to determine whether immunization is an

effective treatment and preventive measure.

(chen et al. 1991, Whitney et al. 1992).

• Randomized clinical trials are the gold standard by which

effectiveness of various treatments or interventions are

determined.

• However, the method by which this is achieved raises the

question as to whether clinical research is good for the

participants.

• Theoretically, the informed consent process ensures that

research subjects are well informed as to the study purpose,

potential risks, potential benefits and alternatives to

participation.

• Concept of evidence based decision making in medicine,

introduced in early 1990s is based on providing the best care

using four sources of information:-

scientific evidence

clinician’s experience & judgement

patient preferences or values

patient clinical circumstances

• When the efficacy of a treatment is assessed in RCT, patient

preference is seldom taken into account.

• Preference expressed by either the patient or clinician may

impact the validity of a RCT.

• Randomizing patients to treatments they do not want may

reduce their participation, follow-up and satisfaction, and

thereby lead to poor outcomes.

• Hewison & Haines argue that limitations imposed by Research

Ethics Committees that allow investigators to only approach

patients who opt in (respond positively to invitational letters to

participate in research) fails to create unbiased samples and

undermines the accurate estimation of outcomes.

• Most funding agencies, including the National Institute of

Dental and Craniofacial Research, are unlikely to support an

application for a randomized clinical trial unless the

investigative team can show through pilot work that the

approach is likely to succeed.

• The presence of a statistically significant difference between

groups is a primary measure of treatment effectiveness, as

viewed by journal reviewers and by agencies such as the Food

and Drug Administration, which regulate claims of devices

and products used to improve oral health.

• This factor makes it possible to game a randomized clinical

trial to produce statistically significant results, even when the

difference between groups is small or not clinically important.

• Even when randomized clinical trials are well designed,

clinical meaningfulness and usefulness remain issues for

consideration by researchers and subjects alike.

Impact of osteoporosis and its treatment

on the risk for periodontitis and the implications

for periodontal therapy

• Is osteoporosis a risk factor for periodontitis?

• Can we identify the signs of osteoporosis from dental

radiographs?

• Do bisphosphonates have an impact on periodontal status?

• Because osteoporotic patients are at higher risk for periodontal

disease and patients with periodontitis are at higher risk for

osteonecrosis of the jaw, periodontal intervention and disease

prevention are imperative.

• Close periodontal maintenance, meticulous monitoring,

understanding of periodontal and implant therapy for the

individual patient at a given time and collaboration with

medical professionals will provide patients with the highest

level of care.

Conclusion

• Research in periodontology continues apace.

• In order to conduct clinically relevant research, we need to ask

the important research questions of the day.

• So that we may undertake research that generates the highest

quality of data so that our findings can be translated into

everyday clinical practice.

References

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• Avula H. Periodontal Research: Basics an beyond - Part III (data

presentation, statistical testing, interpretation and writing of a report). J

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Thank you