Evolving paradigms in the field of periodontal medicine: A review

The association between the oral and systemic health has been a matter of discussion since the focal infection theory of the early 20century. This field has evolved with supportable evidence linking poor periodontal status with systemic diseases and extensive research on this complex relationship has given rise to new field of “Periodontal Medicine.” Although the evidence base is quite large on the impact of systemic disorders on periodontium but a smaller but growing evidence base supports an association between poor periodontal health and systemic diseases. Moreover, today’s era of evidence-based medicine and dentistry provides an excellent environment to examine the possible relationships between oral infection and systemic disorders. Therefore, the purpose of writing this review article is to understand the underlying pathophysiology between periodontal health and systemic health with particular focus on the effects of periodontal disease on systemic outcomes.

Relationship of COVID-19 pathogenesis for periodontal medicine research. Part I: Pathogenesis of COVID-19

Cell invasion mediated by angiotensin-converting enzyme 2 (ACE2) ectoenzyme and cellular proteases, such as trypsin-like proteases, cathepsins, transmembrane serine protease 2 and furin, target different tissues and organs as lung, gut, colon, ileum, kidney, gallbladder, heart muscle, epididymis, breast, ovary, stomach, bile duct, liver, oral cavity, lung, thyroid, esophagus, bladder, breast, uterus, prostate, pancreas, cerebellum, as well as calyx secreting cells in the nasal and sinus tissue. Loss of homeostasis of the renin-angiotensin system deregulates different axes compromising metabolic, cardiorespiratory, renal and hepatic control. SARS-CoV-2 infected cell undergoes pyroptosis and releases molecular patterns associated with damage: pro-inflammatory interleukin (IL) -1b, IL-6, IL-8, IL-10, IL-17, induced protein-10, interferon gamma, interferon gamma-induced protein-10, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein 1α and 1β, monocyte chemotherapy activating protein 1, inflammatory macrophage protein 1a, tumor necrosis-α, and mediators of immune-mediated inflammatory diseases. Cytokine storm and non-neutralizing antibodies produced by B cells circulate, cause/exacerbate damage to various organs. During viral replication and low oxygen saturation, loss of HIF-mediated cell homeostasis can lead to cell death/lysis and tissue damage, related to the hyperinflammatory response. The SARS-CoV-2-ACE2 can increase permeability, inflammation and microbial transmission by bacteremia or endotoxemia, in addition to dysbiosis. Thrombotic potential and the immunoinflammatory imbalance compromise function or lead to injuries and multiple organ failure. Infection by SARS-CoV-2 has the potential to modify the natural history of diseases, the relationships or interactions between the different systems and pathologies and the effects of their treatments, as in periodontal medicine approach.

Relationship of COVID-19 pathogenesis for periodontal medicine research. Part II: Periodontal Medicine

The dysfunctional immunoinflammatory response to SARS-CoV-2 infection leads to excessive infiltration of monocytes, macrophages and T cells, non-neutralizing antibody, systemic cytokine storm, microthrombi mediated by tissue factor and oxidative stress, lower platelet counts, increased D-dimer, C-reactive protein and coagulation abnormalities, increased vascular permeability, pulmonary edema and pneumonia, and widespread inflammation and multi-organ damage. Periodontal diseases have a chronic and multifactorial inflammatory profile, of infectious origin, with bidirectional systemic interactions linked to over 50 systemic conditions/diseases. Immunoinflammatory response of periodontal tissues to the microbial challenge, protective/repair response and the local destruction of periodontium influence and are influenced by systemic conditions/diseases. Renin-angiotensin system/ACE inhibitors are also related to pathogenesis of COVID-19 by SARS-CoV-2-ACE2 and to pathogenesis of periodontitis, through bone resorption regulated by the ACE2/Ang-(1-7)/MasR axis and IL1-b, positive regulation of the kinin/receptor pathway B2 due to Toll-like receptor 2 inflammation and Th1/Th17 responses, the expression of the type 1 angiotensin II receptor in the inflamed gingival tissue, and modulating IL-1β-induced IL-6 production in human gingival fibroblasts. It is possible that SARS-CoV-2 infection increases local inflammatory events in periodontal tissue leading to destruction of periodontal tissues, probably enhanced by the systemic effects of periodontitis. Despite limited or non-existent scientific evidence on the effects of COVID-19 on periodontal diseases and their systemic interactions to date, it is possible to expect its impact on periodontal medicine research from the natural history of periodontal diseases to their pathogenesis and relationship with systemic conditions and response to treatment, as an environmental and acquired risk factor.

Periodontal Medicine: Impact of Periodontal Status on Pregnancy Outcomes and Carcinogenesis

Periodontal medicine is a broad term commonly used to define the relationship between periodontitis and systemic health. Periodontitis is a highly prevalent, chronic multifactorial infectious disease, induced by the dysbiotic biofilm that triggers a persistent systemic inflammation and recurrent bacteremia. There is a growing body of scientific evidence that suggests the potential implication of periodontitis in the causation and progression of various systemic disease and conditions, such as diabetes, cardiovascular disease, pulmonary disease, adverse pregnancy outcomes and cancer. Some studies consider periodontitis as an independent risk factor for preterm birth, growth restriction, low birth-weight and pre-eclampsia. However not all studies support the association. Despite sparse scientific data, some studies indicate that individuals with periodontitis are at increased risk for cancer development, due to the increased inflammatory burden sustained by the presence of periodontal pathogens. This chapter emphasis the relationship between periodontitis and adverse pregnancy outcomes and the underlying mechanisms that link peridontitis to oral carcinogenesis.