many countries1, the burden of periodontitis is expected to increase.
Periodontitis is a chronic multifactorial inflammatory disease associated with dysbiotic plaque biofilms and characterised by progressive destruction of the tooth-supporting tissues. Its primary features are presence of periodontal pocketing and radiographically assessed alveolar bone loss, and can also include signs of gingival inflammation such as redness, swelling and bleeding of the gingiva. Periodontitis is a major public health problem due to its high prevalence, and because it often leads to tooth loss when left untreated. This can result in reduced chewing function and aesthetics, and can further exacerbate oral pathology by leading to pathological tooth migration and occlusal trauma as well as periodontal–endodontic lesions. Therefore, periodontitis directly impairs quality of life4.
Many aspects of the pathophysiology of this inflammatory condition have been characterised. It is recognised that periodontitis has multiple component causes, which when combined in each individual can exceed a threshold for disease initiation5. Examples include:
● an aberrant host immune-inflammatory response to the dental plaque biofilm
● dysbiosis within the biofilm, which contains higher proportions of Gram-negative, anaerobic and facultative bacteria and is microbially less diverse than a healthy biofilm
● genetic and epigenetic factors affecting immune responses and tissue homeostasis
● older age, leading to immune senescence and consequent hyper-inflammatory responses, termed ‘inflammaging’
● modifiable lifestyle factors such as suboptimal oral hygiene, smoking, high stress levels and diets high in refined sugars and low in antioxidant micronutrients
● certain systemic conditions, which affect the immune system and which are discussed in this book.
Environmental factors may also contribute to the onset and progression of periodontitis, but these are currently less well understood. The dysregulated immune reactions ultimately lead to host-mediated damage and breakdown of the periodontal tissues including the alveolar bone. Clinical phenotypes may vary, with some patients presenting with severe periodontal breakdown at a relative young age.
Importantly, there is now abundant evidence that untreated periodontitis promotes the translocation of dental plaque-derived microorganisms, their antigens and certain metabolic components into the circulation, where they may elicit systemic inflammation via an acute-phase response and oxidative stress. This systemic dissemination of antigens and inflammatory mediators has been proposed to form the basis of the association between periodontitis and mortality and also with several systemic non-communicable diseases (NCDs), in conjunction with other mechanisms specific to those diseases6. Numerous clinical and experimental studies have been undertaken in recent decades to better define the association between periodontitis and several systemic NCDs. However, these studies differ markedly in design and quality. In some clinical studies, inconsistent use of case definitions of disease, insufficient control of biases and small sample sizes render results difficult to interpret. Moreover, changes in disease classification systems make comparisons between studies published over several decades challenging. However, the new classification system of periodontal and peri-implant diseases and conditions7, as well as recently updated case definitions for periodontitis8 will help to create greater consistency in clinical periodontal research. Furthermore, the advent of international standards and guidelines for conducting and reporting studies has introduced more consistency and clarity and has improved the quality of those studies adhering to them. Some examples are PRISMA for meta-analyses, CONSORT or STROBE for clinical studies, ARRIVE for animal studies9 and MIQE or MIAPE for experimental ex vivo studies10.
Prior to reading this book, it is important to consider certain principles. First is the principle of evidence-based medicine, which acknowledges that a hierarchy of evidence exists11. This helps practising clinicians and researchers appraise literature and apply evidence to their work, based on the relative strengths and weaknesses of individual study designs. This hierarchy can be depicted as a pyramid, often referred as to the ‘evidence-based medicine pyramid’ (Fig 0-1). The pyramid is divided into levels, where each represents a different type of study design and corresponds to increasing rigour, quality and reliability of the results, and also to higher costs of conducting the relevant studies.
Fig 0-1 Evidence-based medicine pyramid.
The first three levels of the pyramid provide the foundation of knowledge. This background information is important and helpful, but can be heavily influenced by beliefs, opinions and even political views. The top of the pyramid suggests a lower risk of statistical error and bias from confounding variables. Cross-sectional and case-control studies represent the first stage of testing an observation. These studies are conducted in the early stages of research to help identify variables that might be associated with a condition. One of the weaknesses of these designs is that there are often small sample sizes and they are usually non-randomised. The next evidence level is that of prospective cohort studies, which follow people, who are exposed to the suspected risk factor for a disease, over a period of time. Here, causality can be assessed, but cohort studies require large sample sizes and long follow-up times, making them more difficult to apply to diseases with a long latency, such as periodontitis, or for rare conditions. Large double-blind randomised controlled trials are the most reliable study designs and provide the strongest level of evidence for cause and effect relationships. However, these studies are expensive and can be ethically problematic.
Systematic reviews and meta-analyses are located at the top of the pyramid and compare the results of studies side by side. Multiple studies are reviewed using a systematic approach and, where studies are not too dissimilar in design (show low heterogeneity), a statistical summary (meta-analysis) is undertaken that summarises the effect of an intervention, the influence of a risk factor or other outcomes across multiple studies. They are considered as providing the strongest and highest quality of evidence. However, results strongly depend upon the quality and comparability of the included studies. Cochrane publishes systematic reviews with the highest level of rigour and techniques to identify the risks of bias in systematic reviews12.
Next is the distinction between an association and a causal relationship between two or more diseases. An association is when two conditions are related such that they are commonly observed together. A causal relationship between two conditions implies that a change in one is caused by a change in the other. Causal relationships are stronger than associations, but also more difficult to prove. An example for distinguishing between these two is the following fictional research question: if researchers included coffee drinkers and non-coffee drinkers in their cross-sectional study, they may find that a greater proportion of coffee drinkers have periodontitis, compared with non-coffee drinkers. This is an association, which does not imply that coffee drinking causes periodontitis, but merely that coffee drinking and periodontitis are commonly observed together.
What would be more interesting, however, is whether coffee drinking is a component cause or part of the causal pathway of periodontitis. The causal argument can be strengthened in cross-sectional studies by accounting for things that might confound the association. In our example, it may be that people who drink coffee have higher stress levels or are more likely to smoke and therefore more likely to have periodontitis. Hence, smoking and/or stress is confounding the association observed. There are