|Year : 2014 | Volume
| Issue : 2 | Page : 97-101
Current issues in periodontal research methodology
Harpreet Singh Grover, Amit Bhardwaj, Neha Saksena
Department of Periodontics, SGT Dental College, Budhera, Gurgaon, Haryana, India
|Date of Web Publication||7-May-2014|
Department of Periodontics, SGT Dental College, SGT University, Budhera, Gurgaon, Haryana
Periodontal research is increasing nowadays. Various number of scientific papers are published highlighting the various aspects of periodontal research methodology. There are still current issues which need to be emphasized in both basic and clinical periodontal research methodology. The purpose of this review paper is to summarize the unresolved issues pertaining to prevalence, etiology, pathogenesis, diagnosis and therapy in periodontology.
Keywords: Current issues, periodontics, research
|How to cite this article:|
Grover HS, Bhardwaj A, Saksena N. Current issues in periodontal research methodology. SRM J Res Dent Sci 2014;5:97-101
| Introduction|| |
Oral health is an integral element of general health and well-being. Good oral health enables individuals to communicate effectively, to eat and enjoy a variety of foods and is important in overall quality of life, self-esteem and social confidence.  Oral and dental diseases are widely prevalent in India. Though, not life-threatening, these diseases are often very painful, expensive to treat and cause loss of several man days. On the other hand, they are, to a great extent, preventable. The major oral and dental diseases/disorders are:
- Dental caries.
- Periodontal diseases.
- Dentofacial anomalies and malocclusion.
- Edentulousness (tooth loss).
- Oral cancer.
- Maxillofacial and dental injuries.
Among them, periodontal diseases are one of the major causes of tooth loss in India.  Periodontitis is a chronic disease which results in destruction of the periodontal ligament and alveolar bone supporting a tooth and which may eventually lead to tooth loss. Several factors have been associated with the onset and progression of periodontitis, including the presence and overgrowth of certain bacteria, immune function and genetics.  Periodontal (gum) diseases are found to be closely associated with several serious systemic illnesses such as cardiovascular and pulmonary diseases, stroke, low birth-weight babies and preterm labor.  Dentistry is rapidly entering a new era of evidence based practice and society is demanding prevention and treatment that has been proven to be effective in terms of meaningful health outcomes.  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, a hugely prevalent and unpleasant inflammatory disease that can have a significant impact on quality of life.  In spite of the tremendous progress that has been made, many unresolved problems remain. The purpose of this paper is to identify and discuss the some important critical issues pertaining to periodontal research.
| Current issues in prevalence of periodontal diseases|| |
Epidemiology is the science concerned with the factors that influence the distribution and occurrence of health, disease and mortality among groups of individuals.  Based on the existing epidemiologic data, there is appearance of three critical issues.
First, is the prevalence of periodontitis changing?  Extensive epidemiological studies were performed in 1950's and 1960's in numerous countries. One such study by Marshall-Dey et al., observed high prevalence of gingivitis in the early teenage years but decreased to very low values by the late 20's and early 30's. Periodontitis began in late teenage years and by early middle age, virtually 100% of the study population was affected.  The most well-known study presented is the National Health and Nutrition Examination Survey (NHANES) studies covering the years in 1988-1994 and repeated 1999-2000. The results shows that the prevalence of periodontitis for the NHANES 1988-1994 and the NHANES 1999-2000 were 7.3% and 4.2%, respectively, findings that indicate that the prevalence of periodontitis has decreased between the two examinations.  Hugoson and Norderyd reviewed global trends in the change in prevalence of periodontitis over the last 30 years (1973-2003) and the data indicated a possible trend of a lower prevalence of periodontitis in recent years.  Resolution of this issue is critical, since changes in the prevalence of disease impact dental education, individual and group practices, manpower needs, third party carriers and government and other public health programs.
A second unresolved critical issue is to determine the identity and characteristics of this group. Epidemiologic surveys such as that conducted in the United States in 1985-1986 have provided excellent prevalence data for the entire adult population and for various age groups, but they do not permit determination of prevalence in population subgroups or identification of highly susceptible groups of individuals. Studies aimed at identification of high-risk groups and subpopulations are badly needed. 
Third critical issue is the lack of a clear definition of the relationship between microbial tooth deposits and periodontal status. Axelsson et al., in their study have reported that aggressive professional and personal oral hygiene totally prevented attachment loss in 375 people over a period of 15 year.  In marked contrast, Baelum et al., studied a population in Tanzania who practiced little or no oral hygiene and received no professional dental care. While masses of plaque and calculus and severe gingivitis were observed, fewer than 10% of individuals had attachment loss of 6 mm or greater, fewer than 10% of periodontal sites had pocket depths exceeding 3 mm and the oldest individuals in the population still had an average of 23.9 teeth.  Thus, while numerous observations reported over several decades demonstrate a relatively strong association between accumulation of microbial deposits and periodontal deterioration, clearly the relationship is complex and there is not a one-to-one correlation. 
| Current issues in etiology of periodontal diseases|| |
In the early 1960's, there was no clear understanding to the cause of periodontitis, although calculus and other deposits on the teeth were suspected.  The first direct evidence that periodontal diseases in humans are infectious was obtained from the classic experimental gingivitis studies of Loe et al., in 1965.  By the end of the 1960's, there was consensus that periodontitis in humans is an infectious disease process. 
An obvious critical issue is whether a dozen or more microbial species are in fact involved in a meaningful way in the etiology of human periodontitis. If so, periodontitis is unique among human infectious diseases. There appear to be other possible options to account for the observations. 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. Under such conditions, the subgingival flora could present a picture typical of mixed infections where in fact only one or two species are essential. If that were the case, strategies for prevention and control could be quite different from approaches used for a mixed infection involving a dozen or more species.  The fact that almost all of the suspected pathogens are Gram-negative and mostly anaerobic suggests that components such as lipopolysaccharide (LPS) may be such a shared factor. LPS is a component of the cell envelope of all Gram-negative bacteria and its pathogenicity and importance in numerous Gram-negative infectious diseases are well-established.  LPS has been strongly implicated in the pathogenesis of periodontitis.  If LPS plays a role central to the pathogenesis as suggested, the exact species of bacteria involved may be irrelevant.
A second critical issue is whether periodontal infections are a consequence of overgrowth of commensal periodontal microflora or exogenous infections. If infection is a consequence of overgrowth of members of the commensal flora present in most or all individuals, then transmission may not be a critical issue and attention should be focused on determining factors that account for and permit overgrowth to occur at some sites in some individuals but not in others. In contrast, if the bacteria must be acquired for infection to occur, then transmission is a key issue. This question is far from resolution. If transmission is an essential step in the spread of disease and disease onset, our approach to treatment may have to change from focus on a given patient to focus on infected families, with the aim of eliminating disease-causing pathogens. 
The third critical issue, is the unresolved question of the relationship between the presence of a "pathogenic" flora and disease status.  With sufficiently sensitive techniques for detection, putative pathogens can be found commonly in periodontally normal individuals and at healthy sites in mouths of periodontally diseased individuals. , A thresholds exist, below which periodontal sites even though colonized by a given pathogen, are disease inactive, but above which disease activity is observed.  Furthermore, it is now clear that various strains of periodontopathic bacteria such as Porphyromonas gingivalis differ greatly with regard to virulence and pathogenicity.  Thus, while P. gingivalis and other putative periodontal pathogens may be found at high frequency in periodontally normal individuals and sites, they may well be a virulent nonpathogenic strains or clonal types.  Resolution of this issue is made difficult by clonal structure of some of the species.  Very little information exists about clonal virulence; some clones may be virulent and others avirulent and no single clone or group of clones can account for periodontitis. 
An additional fourth critical issue in the area of microbiology, is 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.  Most aspects of the role of environmental factors remain obscure. 
| Current issues in concept of pathogenesis of periodontal diseases|| |
The major research accomplishment of the 1960's was that periodontitis is an infectious disease. Further, in the decade of the 1970's, researchers focused on the role of the host. The first major milestone was publication by Ivanyi and Lehner (1970) of a paper demonstrating that peripheral blood mononuclear cells from patients with periodontitis were sensitized to antigens of their infecting periodontal bacteria. This observation served as a catalyst for investigators world-wide to focus on the role of host defense mechanisms in the etiology of periodontitis.  By the mid-1970's, the focus of research began to change; peripheral blood neutrophils harvested from teenagers with localized juvenile periodontitis were abnormal in that their response to chemo-attractants in vitro was significantly less than that of cells from normal individuals. 
In the 1980's the possible role and importance of B-cells and the humoral immune response became a focus. This was made possible in part by the application of the enzyme-linked immunosorbent assay to periodontal research.  Enormous advances were made in the 1980's in our understanding of mechanisms of tissue destruction in chronic inflammatory diseases, including periodontitis. A very recent development has been the realization that fibroblasts can play a major role in destruction of the very tissues they produce and maintain.  Advances in our understanding of pathogenesis of periodontitis have major implications for development of future therapies. Over time, we will undoubtedly develop ways to control gene activation and thereby block destruction of the periodontal tissues.  Clinical trials have been conducted on an oral rinse containing the anti-inflammatory drug ketorolac, which, when used twice each day, blocks alveolar bone destruction by inhibiting the production of prostaglandin.  Furthermore, use of the chemically modified tetracyclines which inhibit the activities of the metalloproteinases shows great promise in arresting the destruction of the connective tissues. 
| Current issues in diagnosis of periodontal diseases|| |
Diagnosis implies that a biological phenomenon can be comprehended based on some of its key features and that this information has an impact on the decision on how to improve the situation. Diagnostic procedures may be used to: Identify people at risk of developing disease (at risk); detect early stage disease in clinically asymptomatic individuals (screening); classify disease categories (classification); predict likely responders to specific treatments (treatment planning); monitor treatment efficacy and detect disease recurrence (monitoring). 
Using traditional methods of periodontal diagnosis, including assessment of pocket depth, attachment level, bleeding and radiographic manifestations of alveolar bone loss, we are unable to distinguish between disease active and disease inactive pockets. Our inability to make the distinction between diseased and healthy pockets is the central critical issue in periodontitis.  With a new awareness that not all individuals were equally susceptible to periodontal disease, scientists turned their attention to a study of "risk" for disease.  Risk factors are participants in the causation of disease, such as smoking and lung cancer, while risk indicators may be associated with a disease but have not been proven to be linked to causation.  From the early 1990's, reports describing the role of risk in periodontal disease susceptibility increased awareness of the importance of risk. Clinicians and investigators began to examine the role of various environmental, acquired and inherited risk factors for periodontal disease, including diabetes mellitus, tobacco smoking, poor oral hygiene, specific microflora, stress, race and gender. 
There are occasions when different tests can be used to make the same diagnosis. Parameters with a diagnostic potential in the context of periodontal health and disease are often highly correlated with each other. Sites with increased probing depths, for example, have an increased tendency to bleed, are associated with anaerobic Gram-negative bacteria and present high levels of various biochemical markers of inflammation. If a diseased site is detected, similar ones will be present elsewhere in the same dentition. Thus, the utility of assessing the same parameter at multiple sites or testing multiple parameters in the same patient needs to be evaluated appropriately. 
Based on genomic and proteomic techniques, a new class of diagnostic tools is currently being developed. These new methods will provide exciting new answers to old questions but will also confront us with new problems. Based on genomic and proteomic techniques, a new class of diagnostic tools is currently being developed. These new methods will provide exciting new answers to old questions but will also confront us with new problems. Future pharmacodiagnostic tests will aim at molecular signatures with response to a particular drug, allowing efficient identification of patient subpopulations. The application of this pharmacogenetic knowledge for the selection and dosage of drugs in clinical routine will require extensive research in properly designed prospective studies. 
| Current issues in periodontal therapy|| |
Surgical therapy aimed at elimination of periodontal pockets and restoration of the normal physiological contour to the marginal alveolar bone came into widespread use in the 1960's. In the 1970's, these surgical techniques were honed to perfection.  While surgical treatments were effective in arresting the progress of periodontal tissue destruction in most patients, some clinicians and investigators began to question whether surgery was in fact necessary. 
Firstly, 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. Nevertheless, the outcome of these therapies is not always predictable. We badly need extensive basic and clinical research aimed at improving the success rate of various grafting and guided tissue regeneration therapies and extending their usefulness to more advanced lesions. 
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. 
Periodontitis is an infectious disease. In most infections, the host mounts an immune response to the antigens of the infecting bacteria which arrests the disease and clears the infecting microorganisms. Several questions arise regarding periodontitis, leading to the third critical issue: Do periodontitis patients produce antibodies to their infecting bacteria and if not, why? If so, are they protective and if not, why? It is shown that roughly half of young adults with severe periodontitis fail to produce serum antibodies to the infecting bacteria. In those who do, the antibodies are not effective in opsonization and in enhancing phagocytosis and killing of bacteria.  Treatment by scaling and root planing is known to result in bacteremia. They suspected that such treatment could be a form of vaccination and tested the idea 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.  They postulated that patients who do not respond favorably to therapy may not have the capacity to mount a protective immune response.
Ethical issues in periodontal research
The Research participants require full disclosure of what the research will provide those regarding short-term and long-term gains, if any and the potential sequelae of their participation.  Researchers have the ethical responsibility to consider the informed consent process as it relates to the subject's health literacy, potential for therapeutic and procedural misperceptions and need for referral and/or supportive periodontal therapy once the study is completed. 
Information published by the Food and Drug Administration suggests that lapses in researcher judgment and ethics continue to occur, resulting in the disqualification of researchers for significant deficiencies in the research process.  The most common problems include failures to obtain Institutional Review Board approval, to obtain patient informed consent, to follow protocol, to administer the study drug, to report adverse events and/or to maintain good study records. 
In periodontics, complex randomized clinical trials involving sophisticated techniques and materials like surgical interventions that compare various types and combinations of bone grafting materials trials may not be amenable to blinding, which is the standard to minimize the influence of researcher and patient expectations. ,
Miller and Brody have stated that there is a moral peril in financial relationships between investigators and industry because investigators may come to identify with corporate goals by participating in trials that are biased or by framing results favorable to sponsors. 
Several authors have suggested that researchers have significant obligations to subjects that must be respected. These obligations include: Ensuring that the study has social or scientific value (as subjects are volunteering their time and are often willing to expose themselves to some level of risk); clearly articulating that the risk-benefit ratio falls on the side of society rather than on the individual subject; not exploiting subjects vulnerable because of their health, social status or access to care; and avoiding paternalistic decision-making on behalf of subjects who might want to participate for the greater good of society. Fundamental to these obligations is bearing in mind the potential quandary between subjects autonomy to make choices and their health literacy. ,
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