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Critical issues in
periodontal research
Khushbu Mishra
• Guidedby:-
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/prev
alence
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
• Avula H. Periodontal research: Basics and beyond - Part II (ethical issues,
sampling outcome measures and bias). J Indian Soc Periodontol
2013;17:571-6.
• Avula H, Pandey R, Bolla V, Rao H, Avula JK. Periodontal research: Basics
and beyond - part I (defining the research problem, study design and levels
of evidence). J Indian Soc Periodontol 2013;17:565-70
• Avula H. Periodontal Research: Basics an beyond - Part III (data
presentation, statistical testing, interpretation and writing of a report). J
Indian Soc Periodontol 2013;17:577-82.
• Williams RC. Understanding and managing periodontal diseases: a notable
past, a promising future. J Periodontol. 2008; 79:1552-1559..
• Kornman KS. Mapping the pathogenesis of perio - dontitis: a new look. J
Periodontol. 2008;79:1560-1568.
• Offenbacher S, Barros SP, Beck JD. Rethinking perio - dontal
inflammation. J Periodontol. 2008; 79:1577-1584
• Lindhe J, Haffajee AD, Socransky SS. Progression of periodontal disease in
adult subjects in the absence of periodontal therapy. J Clin Periodontol.
1983; 10:433-442.
• Armitage GC. Learned and unlearned concepts in periodontal diagnostics:
a 50-year perspective. Periodontol 2000 2013; 62:20-36.
• Lisa J, Heitz-Mayhield, Lang NP. Surgical and nonsurgical periodontal
therapy. Learned and unlearned concepts. Periodontol 2000 2013; 62:218-
231.
Thank you

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Critical issues in periodontal research khushbu

  • 1. Critical issues in periodontal research Khushbu Mishra
  • 3. 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.
  • 4. • "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).
  • 5. • In spite of the tremendous progress that has been made, many unresolved problems remain.
  • 8. • 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.
  • 10. • Thus, these studies demonstrated a prevalence much lower than expected, with severe periodontitis observed in a very small proportion of the population.
  • 11. • 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.
  • 12. • 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.
  • 13. • Is the prevalence of periodontitis changing?
  • 14. • 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)
  • 15. • 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?
  • 16. • 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.
  • 17. • 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 ….
  • 20. • Whether a dozen or more microbial species are in fact involved in a meaningful way in the etiology of human periodontitis?
  • 21. • 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.
  • 22. • whether periodontal infections are a consequence of overgrowth of commensal periodontal microflora or exogenous infections?
  • 23. • 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.
  • 24. • 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).
  • 25. • Question of the relationship between the presence of a "pathogenic" flora and disease status.
  • 26. • 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.
  • 27. • 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).
  • 28. • The role that environment and ecology play in bacterial gene expression, genetic change, and virulence….
  • 29. • 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.
  • 31. • 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.
  • 32. • 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.
  • 33. • 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.
  • 34. Mechanism of tissue destruction Heath et al. 1987; Meikel et al. 1989; Birkedal-Hansen et al. 1993
  • 36. • Over time, we will undoubtedly develop ways to control gene activation, and thereby block destruction of the periodontal tissues.
  • 37. 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.
  • 38. 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).
  • 39. • 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.
  • 40. • Do periodontitis patients produce antibodies to their infecting bacteria? • and if not, why? • If so, are they protective, and if not, why?
  • 41. • 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).
  • 42. • 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)
  • 43. • 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).
  • 44. • 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).
  • 45. • 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.
  • 46. • 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.
  • 47. • 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
  • 48. • 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.
  • 49. • 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.
  • 50. • 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.
  • 51. • 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.
  • 52. 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?
  • 53. • 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.
  • 54. 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.
  • 55. References • Avula H. Periodontal research: Basics and beyond - Part II (ethical issues, sampling outcome measures and bias). J Indian Soc Periodontol 2013;17:571-6. • Avula H, Pandey R, Bolla V, Rao H, Avula JK. Periodontal research: Basics and beyond - part I (defining the research problem, study design and levels of evidence). J Indian Soc Periodontol 2013;17:565-70 • Avula H. Periodontal Research: Basics an beyond - Part III (data presentation, statistical testing, interpretation and writing of a report). J Indian Soc Periodontol 2013;17:577-82. • Williams RC. Understanding and managing periodontal diseases: a notable past, a promising future. J Periodontol. 2008; 79:1552-1559.. • Kornman KS. Mapping the pathogenesis of perio - dontitis: a new look. J Periodontol. 2008;79:1560-1568. • Offenbacher S, Barros SP, Beck JD. Rethinking perio - dontal inflammation. J Periodontol. 2008; 79:1577-1584
  • 56. • Lindhe J, Haffajee AD, Socransky SS. Progression of periodontal disease in adult subjects in the absence of periodontal therapy. J Clin Periodontol. 1983; 10:433-442. • Armitage GC. Learned and unlearned concepts in periodontal diagnostics: a 50-year perspective. Periodontol 2000 2013; 62:20-36. • Lisa J, Heitz-Mayhield, Lang NP. Surgical and nonsurgical periodontal therapy. Learned and unlearned concepts. Periodontol 2000 2013; 62:218- 231.