Periodontal Disease


Continuing Education Activity

Periodontal diseases are disease processes involving the periodontium, a term used to describe the supportive apparatus surrounding a tooth, which includes the gingival tissue, alveolar bone, cementum, and periodontal ligament. Gingivitis is the mildest form of periodontal disease and can be found in up to 90% of the population. It is a reactive condition that is reversible upon the improvement of oral hygiene. Periodontitis is when the periodontal condition has progressed beyond gingivitis into a chronic, destructive, irreversible inflammatory disease state. The bacteria then can penetrate deeper into the tissues and surrounding periodontium. This triggers a host response in an attempt to defend against the invading bacteria. However, during the process of protecting against the bacteria, the host defenses also lead to the destruction of the periodontium. Periodontitis leads to loss of attachment of the periodontium, which subsequently progresses to alveolar bone loss, potentially resulting in loss of the affected tooth. This activity describes the evaluation and management of periodontal diseases and highlights the role of the interprofessional healthcare team in identifying and treating patients with these conditions.

Objectives:

  • Identify the etiology of periodontal diseases.
  • Describe and summarize the pathophysiology of periodontal diseases.
  • Outline the treatment and management options available for periodontal diseases.
  • Review interprofessional team strategies for improving care coordination and communication to advance the treatment of periodontal diseases and improve outcomes.

Introduction

Periodontal diseases are disease processes involving the periodontium, a term used to describe the supportive apparatus surrounding the tooth, which includes the gingival tissue, alveolar bone, cementum, and periodontal ligament.

Gingivitis is the mildest form of periodontal disease and can be found in up to 90% of the population. It is a term used to describe the inflammation of the gingiva due to the accumulation of bacteria and debris between the gum line and tooth, also known as dental plaque. Gingivitis is a reactive condition that is reversible upon the improvement of oral hygiene. Periodontitis is when the periodontal condition has progressed beyond gingivitis into a chronic, destructive, irreversible inflammatory disease state. The bacteria then can penetrate deeper into the tissues and surrounding periodontium. This triggers a host response in an attempt to defend against the invading bacteria. However, during the process of protecting against the bacteria, the host defenses also lead to the destruction of the periodontium. Periodontitis leads to loss of attachment of the periodontium, which subsequently progresses to alveolar bone loss, potentially resulting in loss of the affected tooth [1][2][3].

In 2017, the American Academy of Periodontology, in collaboration with the European Federation of Periodontology, devised a new classification of periodontal and peri-implant diseases. In this new classification, periodontitis can be subdivided into three categories:

  • Necrotizing periodontal diseases
  • Periodontitis
  • Periodontitis as a manifestation of systemic diseases

Necrotizing periodontal disease refers to a virulent, rapidly progressing disease that is mostly seen in immunosuppressed patients, such as those with HIV. This form of periodontal disease includes necrosis of the gingiva found between the teeth, bleeding, and associated pain [4][5].

Etiology

Periodontal diseases arise as a result of several factors, including both patient-specific risk factors and inadequate oral hygiene.

The risk factors can be subdivided into modifiable risk factors, including smoking tobacco, poor oral hygiene, diabetes mellitus, and pregnancy, and non-modifiable risk factors, like age and heredity, including genetic diseases.

Inadequate oral hygiene practices play a significant role in the initiation and development of periodontal diseases. Improper oral hygiene techniques can lead to the build-up of bacteria and plaque on the teeth, initiating gingivitis and potentially progressing to periodontitis. This relationship has been demonstrated in the literature, with the increasing build-up of dental plaque being directly associated with increased severity and prevalence of periodontal diseases. 

With inadequate oral hygiene, anaerobic organisms responsible for the progression of periodontal diseases can colonize in deeper areas of the periodontium where they can then execute their destructive actions. The main bacteria found in periodontitis include Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. When allowed to penetrate deep into the periodontium, these organisms produce inflammation by triggering the release of inflammatory mediators, and other defensive products from the host [6][7][8][9][1].

The most noteworthy major modifiable risk factor of periodontal diseases is tobacco smoking. It can increase the risk for periodontal diseases 5-20 fold, with an odds ratio of 5.4 between smoking and chronic periodontitis. Additionally, tobacco smoking is associated with greater levels of bone loss, attachment loss, deep periodontal pockets associated with the disease, and tooth loss, as compared to non-smokers. In addition to the increased severity of periodontal diseases, tobacco smoking is also associated with a significant decrease in the effectiveness of treatments [10][11][12][13][14][15][6].

Diabetes mellitus is also a major contributor to periodontal diseases. This disease is associated with certain pathologic processes that enhance periodontal breakdown, such as impaired wound healing. Further associations between diabetes mellitus and periodontal diseases can be found in the complications subheading. In patients with diabetes mellitus, severe periodontal disease correlates to an increased mortality risk as compared to patients with the absent or mild disease [7][16].

Pregnancy is associated with fluctuations in hormone levels, changes that have been shown to promote an inflammatory response that is linked to gingivitis and periodontitis. Although not clearly understood, maternal hormones were shown to be positively correlated with levels of Porphyromonas gingivalis, a key microbe in the progression of periodontal disease. Both hypoestrogenism and hyperestrogenism have been shown to contribute to gingivitis [17][18][19][20].

Age is a non-modifiable risk factor of periodontal diseases discussed extensively in the literature. Older individuals have been shown to have a more severe inflammatory response to plaque deposition, with the response containing a larger number of inflammatory cells. This aggregation of inflammatory cells puts older individuals at greater risk of experiencing the destruction of the periodontium. Additionally, due to aging being associated with a loss of dexterity, older individuals tend to be less proficient with their oral hygiene practices. This results in higher plaque levels, which is a known risk factor for the development of periodontal diseases. Furthermore, research has demonstrated increased clinical attachment loss (CAL) in individuals aged 60 to 90 as compared to those below the age of 5050 [21][7][22][23].

Lastly, several genetically linked systemic disorders have been shown to manifest as periodontal diseases. The etiology of the development of periodontal diseases within these systemic diseases has also been documented in the literature. These disorders include Down syndrome, Ehlers-Danlos syndrome (types IV and VIII), and Crohn disease [24][25][26].

Epidemiology

Periodontal diseases can be seen in up to 90% of the global population, making it the most common oral disease. In the United States alone, cross-sectional studies show that approximately 50% of adults currently have some form of gingivitis, and up to 80% have experienced some form of periodontal disease in their life. Certain groups have been shown to have an increased incidence of periodontal diseases. These groups include older individuals, males, and African-Americans. Lower-income and education levels were also associated with severe periodontitis [1][6][7][27].

Pathophysiology

The commensal oral bacteria are responsible for the initiation and propagation of the disease through the process of dysbiosis, or microbial imbalance. The disease proceeds cyclically with periods of activity and quiescence until therapeutic action is taken, or the tooth and surrounding structures are destroyed by the disease process that may result in the loss of the tooth. As periodontal disease progresses from gingivitis to periodontitis, a greater number of anaerobic organisms colonize deeper periodontal pockets, such as Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, which triggers the host inflammatory response. This response includes the production and dissemination of C-reactive protein (CRP), a biomarker of inflammation, as well as various neutrophil and macrophage compounds such as tumor necrosis factor-alpha (TNF-a), matrix metalloproteinases (MMPs), and interleukins (IL-1 and IL-8). An elevated serum CRP level suggests that the inflammation arising as a result of periodontitis may correlate with cardiovascular pathology. Additionally, smoking creates an increasingly favorable environment for the growth of periodontal pathogens, thus furthering the disease process [2][1][24][28][29][9].

Histopathology

Page and Shroeder first described the histopathology of periodontal diseases. There are four distinct stages of disease progression, and each stage takes into consideration both clinical and histopathological appearances of tissues.

The initial lesion is marked by a plaque that results in vascular changes and intercellular gap formation that leads to increased amounts of gingival crevicular fluids (GCF). Adhesion molecules attract polymorphonuclear neutrophils to the site of the lesion. T lymphocytes specifically alter the fibroblasts of the affected area. Clinically, this stage of the lesion is benign.

As redness at the site develops, it is known as the early lesion. Polymorphonuclear neutrophils (PMN) infiltrate the area and clear the fibroblasts that are undergoing apoptosis. The infiltration also causes collagen fiber breakdown leading to an increased amount of space for infiltrates. There is a degradation of the marginal connective tissue matrix.

The established lesion is predominantly dominated by leukocyte aggregation and B cells, either plasma cells or lymphocytes, that initiate the transformation of the site by changing both the junctional epithelium and sulcular epithelium into the pocket epithelium. The pocket epithelium is extremely permeable and vulnerable. Clinically, this manifests as bleeding upon gentle probing of the gingival tissues.

The final stage, known as advanced lesion, is a transition to periodontitis. The advanced lesion is created by the migration of biofilm to the pocket, which gives an ideal niche for anaerobic bacteria to proliferate. There is an irreversible loss of attachment and bone loss that can be seen histologically and clinically. Loss of gingival fibers and loss of the alveolar bone are the hallmarks of this stage. This lesion is highly influenced by the microbial factors themselves and can cause several changes depending on the host and organism [30][31][30].

History and Physical

Periodontal diseases can manifest in several ways. Most often, early stages are not recognized as they are asymptomatic inflammatory responses in the oral cavity. Often, the first reported symptom of periodontal diseases is bleeding during brushing or flossing. Another symptom that may be noted by the patient is halitosis. More severe symptoms at the time of presentation include pain and tenderness during chewing of specific substances, sensitive teeth, receding gums, the formation of discoloring plaque, tooth mobility, and even loss of teeth.

Chronic periodontitis can present in patients of any age, but most often affects middle-aged to older adults. The severity of the disease is based on the amount of clinical attachment loss (CAL). It is described as mild when the CAL is 1 to 2 mm, moderate the CAL is 3 to 4 mm, or severe when the CAL is more than 5 mm [32].

A more rapidly progressing form of periodontitis (formerly termed "juvenile periodontitis" and "aggressive periodontitis") presents with similar symptoms, but this form of condition has a predilection to younger patients. This form of the condition tends to target specific teeth (most commonly first molars and incisors) and often occurs in the absence of the significant plaque accumulation noted in chronic periodontitis.

Routine dental screenings are invaluable in recognizing early disease states and directing early intervention. A review of the patient medical history and comorbidities raises the awareness of dental care providers. Inspection of the tooth and gum can reveal inflammation of the gum line, receding gums, and sometimes even pus-filled pockets. Dental probes are used to measure dental pockets adjacent to several teeth. A probing depth of greater than 3 mm may be indicative of periodontal disease. Depths greater than 6 mm often require more aggressive therapy as these spaces are more difficult to treat mechanically. Dental X-rays also can check for bone loss in accordance with the depth of pocket and disease severity [33][1].

Evaluation

The diagnosis of periodontal diseases requires the comparison of findings in relation to the normal periodontium. This comparison uses visual inspection, periodontal probing, and evaluation of bone levels seen radiographically. The normal periodontium consists of stippled, pale pink gingiva that is well adapted to the underlying bone. Between the gingiva and the tooth, there is a 1 to 3 mm physiological sulcus that normally displays no signs of bleeding. Comparatively, signs of periodontal disease include active bleeding in response to mild or no tissue manipulation, pain, bad taste/odor, periodontal pocketing, radiographic bone loss, clinical attachment loss, and tooth loss. The radiographs of a patient with periodontitis will show an alveolar bone loss in close proximity to a deep periodontal probing depth. These findings suggest that there is a deep periodontal pocket associated with the tooth that contains the periodontal pathogens that are actively triggering the host response. If left untreated, the bone loss will progress until there is inadequate tooth support, and the associated tooth will become mobile and eventually be lost [3][2].

Treatment / Management

The treatment of periodontal disease involves a step-wise approach beginning with more conservative options. The initial phase of treatment for all forms of periodontitis is a professional dental cleaning, which includes scaling of the teeth, and root planning to remove dental plaque and calculus found both above and below the gum line. A major part of this dental cleaning is the oral hygiene instruction given by the dental professional to the patient to improve their at-home oral hygiene routine. Following the completion of the cleaning appointment, the patient should return to the dentist for a reevaluation of the periodontal condition, which involves an examination that observes the state of the periodontium, and measures probing depths to see if the disease process was arrested. If the resolution of the condition can be confirmed, the patient should return to the dentist for regularly scheduled cleanings as periodontitis is a chronic disease that can reactivate if given the proper environment [2][1][6].

The most important management of the periodontal disease is the treatment of risk factors.

Inadequate oral hygiene is one of the key initiators of periodontal disease. Prevention of poor oral hygiene practices involves the promotion of proper self-performed oral hygiene as well as professional maintenance at regular intervals depending on the individual patient’s risk. The self-care recommended uses a three-step daily regimen that includes brushing, flossing, and rinsing. Referral to a dentist for professional cleaning and scheduled follow-up to monitor the progression of the disease is also recommended [2][6][16].

Another major modifiable risk factor that must be addressed is tobacco smoking. Tobacco smoking has not only been shown to significantly increase the risk of developing periodontal disease but is also associated with a more severe disease course, and a significantly lower response to periodontal therapies. The link between smoking and periodontal disease decreases with smoking cessation [10][11][34][35].

Diabetes mellitus has well-documented links to periodontal disease; it may enhance the destruction seen in periodontitis. Additionally, poor glycemic control is linked to increased disease progression. Uncontrolled glucose levels are associated with higher mortality if the patient has severe periodontal disease. Therefore, the management of diabetes mellitus and prediabetes mellitus may be required to improve the outcomes of periodontal therapy [7][36][16].

In cases of persistent periodontal disease that is refractory to non-pharmacologic therapies, antibiotics can be administered both locally and systemically, depending on the severity of the disease.

Chlorhexidine gluconate is a common antimicrobial compound used in adjunction to mechanical periodontal therapy. It is generally administered as a mouth rinse, but can also be used as a gel, varnish, and subgingival chip. Using chlorhexidine, in addition to regular toothbrushing, can lead to a reduction of dental plaque build-up and thus can be very beneficial in the treatment of chronic periodontitis. There is a relatively new advancement in pharmacotherapy for periodontal disease. It is a chlorhexidine gluconate chip that is inserted into the periodontal pocket following completion of cleaning and provides long-term, sustained-release of chlorhexidine gluconate into the affected area [37][38][39].

Another option is an adjunctive antimicrobial compound used following mechanical periodontal therapy. It is composed of minocycline hydrochloride microspheres that are placed into the surrounding pockets following mechanical debridement. Its effect is similar to the chlorhexidine chip in that it effectively reduces dental plaque build-up [40].

Although rare, systemic antibiotics are sometimes indicated, such as in the case of persistent deep periodontal pockets. The most common antimicrobial agents prescribed include:

  • Tetracyclines
  • Penicillins
  • Macrolides
  • Quinolones
  • Cephalosporins 
  • Nitroimidazole compounds

These pharmacological agents vary in modes of action and can be prescribed to patients with a range of susceptible microorganisms, including those with antibacterial resistance. Additionally, these agents can be prescribed alone or in combination to expand their use further [41][42][43].

More severe cases of periodontal diseases should be referred to a periodontist. In addition to the modalities described above, periodontal surgery may be required to effectively clean a periodontal pocket and/or attempt to regain bone and attachment that has been lost from the destructive disease process.

Differential Diagnosis

  1. Periodontal abscesses are localized purulent infections found in the periodontium surrounding the tooth [44][45][46].
  2. Endodontic lesions are localized infections originating from the tooth pulp that may seep out of the root tissue into the surrounding periodontium and appear to be of periodontal origin [44][45][46].
  3. Leukemia can manifest as gingival enlargement with bleeding gums and can mimic periodontal diseases, such as gingivitis [47].
  4. A side effect of certain medications, including calcium channel blockers, immunosuppressants, and anticonvulsants, is gingival hyperplasia, which can clinically resemble gingivitis [48][49].
  5. Squamous cell carcinoma can cause extensive bone loss, and mimic periodontal disease that is refractory to mechanical and pharmacological therapies [50][51].

Staging

The most recent staging guidelines were published in 2017 and divides the classification into staging and grading of periodontitis.

Staging is based on the severity and extent of the management required and is given a stage depending on factors such as clinical attachment loss, radiographic bone loss, and tooth loss.

  • Stage I: Initial periodontitis
  • Stage II: Moderate periodontitis
  • Stage III: Severe periodontitis with the potential for additional tooth loss
  • Stage IV: Severe periodontitis with the potential for loss of dentition

Grading is a measure used to describe the rate of progression of the disease based on the evidence for associated risk factors such as smoking and diabetes mellitus [4][52]:

  • Grade A: low rate of progression
  • Grade B: expected progression
  • Grade C: high risk of progression

Prognosis

The prognosis of periodontal disease depends on the stage and grade of the disease, the presence of contributory factors, and the treatment and management of the disease. The higher the stage and the more rapidly progressive the grade, the worse the prognosis of the disease. Additionally, factors such as tobacco smoking and uncontrolled diabetes mellitus affect the prognosis of the disease.

The guide used to determine the prognosis of the disease was developed by McGuire and is used to predict the survival of individual teeth. Based on a combination of factors, each tooth is given a score of good, fair, poor, questionable, or hopeless. The guide is useful and should be used in all cases of the initial evaluation of the disease, re-evaluation following periodontal therapy, and long-term monitoring. The guide makes use of factors such as patient age, medical status, oral hygiene status, socioeconomic status, type and distribution of bone loss, and current periodontal condition [53][54].

Complications

One of the most noted and direct consequences of periodontal disease is tooth loss which arises as the progression of the disease leads to increased destruction of the periodontium, including the periodontal ligament and alveolar bone that normally anchor the teeth. However, periodontal disease not only affects the oral tissues, but has also been shown linked to several systemic diseases such as diabetes mellitus, cardiovascular disease, and pregnancy complications such as preterm low-birth-weight infants [55].

Patients with diabetes mellitus are shown to be at an increased risk of developing periodontal disease. It has been estimated that patients with type 2 diabetes mellitus and severe periodontal disease have a 3.2 times greater mortality risk than people with diabetes without periodontal disease. Some of the characteristic pathological processes of this association include impaired wound healing and host responses and enhanced collagenolytic activity resulting in an increased breakdown of the periodontium. Additionally, poorly controlled diabetes is associated with the increased severity of these effects. Periodontal disease may act as an initiator of insulin resistance as research has demonstrated that periodontal disease is associated with hyperglycemia, impaired glucose tolerance, and poor glycemic control. Furthermore, the hyperglycemia experienced by this population may enhance the proliferation of the bacteria responsible for periodontal disease, thus increasing its severity in those with diabetes [7][16][56][57][24][58].

Periodontal disease is associated with cardiovascular disease. As previously mentioned, the key biomarker of inflammation, C-reactive protein (CRP), has been seen to be elevated in patients with periodontal disease. CRP is also a factor associated with cardiovascular disease and cardiovascular events. There is a direct link between the bacterial level found in periodontal disease and atherosclerosis. However, a causal relationship has not yet been established [59][24][60][61][62][61].

Another major complication associated with periodontal disease is pre-term low birth weight infants. There is a significant correlation between the presence of maternal periodontal disease and infant birth weight. As periodontal disease increases from none to severe, infant birth weight tends to decrease, as shown in prior research [63][64][65][66][67].

Deterrence and Patient Education

Provide patients with education about how to modify risk factors such as smoking and oral hygiene. Interdisciplinary healthcare professionals should work together to monitor and treat underlying causes, including diabetes mellitus. The importance of regular dental check-ups and home oral hygiene should be reinforced to the general population.

Enhancing Healthcare Team Outcomes

Periodontal diseases are the most common diseases found in the oral cavity. The majority of risk factors influencing the onset and progression of periodontal diseases are considered to be modifiable. With proper guidance and instruction, the interprofessional healthcare team may be able to reduce the risk of occurrence. These modifiable risk factors include inadequate oral hygiene regimens, tobacco smoking, and diabetic control. It is the responsibility of clinicians to understand the importance and impact of these risk factors when assessing patients on their risk for developing periodontal diseases. Providers are responsible for screening and initial treatment. Referal to periodontal specialists can be considered. Only by practicing effective risk assessment can these patients receive the care they require. Furthermore, because periodontal disease can arise as a result of systemic and genetic diseases, it is not solely the responsibility of the dental professional to be aware of these at-risk populations. Therefore, the diagnosis, treatment, and maintenance of periodontal disease require a holistic approach between hygienists, dentists, and periodontists to most effectively identify and treat the affected patients. With an interprofessional team approach, patients with periodontal disease can experience improved outcomes. [Level 5]


Article Details

Article Author

Noah Gasner

Article Editor:

Ryan Schure

Updated:

4/21/2021 1:46:52 PM

PubMed Link:

Periodontal Disease

References

[1]

Pihlstrom BL,Michalowicz BS,Johnson NW, Periodontal diseases. Lancet (London, England). 2005 Nov 19;     [PubMed PMID: 16298220]

[2]

Kinane DF,Stathopoulou PG,Papapanou PN, Periodontal diseases. Nature reviews. Disease primers. 2017 Jun 22;     [PubMed PMID: 28805207]

[3]

Highfield J, Diagnosis and classification of periodontal disease. Australian dental journal. 2009 Sep;     [PubMed PMID: 19737262]

[4]

Babay N,Alshehri F,Al Rowis R, Majors highlights of the new 2017 classification of periodontal and peri-implant diseases and conditions. The Saudi dental journal. 2019 Jul;     [PubMed PMID: 31337931]

[5]

Todescan S,Nizar R, Managing patients with necrotizing ulcerative periodontitis. Journal (Canadian Dental Association). 2013;     [PubMed PMID: 23763731]

[6]

Ridgeway EE, Periodontal disease: diagnosis and management. Journal of the American Academy of Nurse Practitioners. 2000 Mar;     [PubMed PMID: 11033686]

[7]

Nazir MA, Prevalence of periodontal disease, its association with systemic diseases and prevention. International journal of health sciences. 2017 Apr-Jun;     [PubMed PMID: 28539867]

[8]

Albandar JM, Global risk factors and risk indicators for periodontal diseases. Periodontology 2000. 2002;     [PubMed PMID: 12102708]

[9]

Zee KY, Smoking and periodontal disease. Australian dental journal. 2009 Sep;     [PubMed PMID: 19737267]

[10]

Bergström J, Tobacco smoking and chronic destructive periodontal disease. Odontology. 2004 Sep;     [PubMed PMID: 15490298]

[11]

Hilgers KK,Kinane DF, Smoking, periodontal disease and the role of the dental profession. International journal of dental hygiene. 2004 May;     [PubMed PMID: 16451463]

[12]

Brothwell DJ, Should the use of smoking cessation products be promoted by dental offices? An evidence-based report. Journal (Canadian Dental Association). 2001 Mar;     [PubMed PMID: 11282035]

[13]

Grossi SG,Skrepcinski FB,DeCaro T,Zambon JJ,Cummins D,Genco RJ, Response to periodontal therapy in diabetics and smokers. Journal of periodontology. 1996 Oct;     [PubMed PMID: 8910828]

[14]

Feldman RS,Bravacos JS,Rose CL, Association between smoking different tobacco products and periodontal disease indexes. Journal of periodontology. 1983 Aug;     [PubMed PMID: 6578319]

[15]

Grossi SG,Zambon JJ,Ho AW,Koch G,Dunford RG,Machtei EE,Norderyd OM,Genco RJ, Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. Journal of periodontology. 1994 Mar;     [PubMed PMID: 8164120]

[16]

Douglass CW, Risk assessment and management of periodontal disease. Journal of the American Dental Association (1939). 2006 Nov;     [PubMed PMID: 17035673]

[17]

Daalderop LA,Wieland BV,Tomsin K,Reyes L,Kramer BW,Vanterpool SF,Been JV, Periodontal Disease and Pregnancy Outcomes: Overview of Systematic Reviews. JDR clinical and translational research. 2018 Jan;     [PubMed PMID: 30370334]

[18]

Uwitonze AM,Uwambaye P,Isyagi M,Mumena CH,Hudder A,Haq A,Nessa K,Razzaque MS, Periodontal diseases and adverse pregnancy outcomes: Is there a role for vitamin D? The Journal of steroid biochemistry and molecular biology. 2018 Jun;     [PubMed PMID: 29341890]

[19]

Carrillo-de-Albornoz A,Figuero E,Herrera D,Bascones-Martínez A, Gingival changes during pregnancy: II. Influence of hormonal variations on the subgingival biofilm. Journal of clinical periodontology. 2010 Mar;     [PubMed PMID: 20088983]

[20]

Wu M,Chen SW,Jiang SY, Relationship between gingival inflammation and pregnancy. Mediators of inflammation. 2015     [PubMed PMID: 25873767]

[21]

Persson GR, Periodontal complications with age. Periodontology 2000. 2018 Oct;     [PubMed PMID: 30198125]

[22]

Grodstein F,Colditz GA,Stampfer MJ, Post-menopausal hormone use and tooth loss: a prospective study. Journal of the American Dental Association (1939). 1996 Mar;     [PubMed PMID: 8819784]

[23]

Rheu GB,Ji S,Ryu JJ,Lee JB,Shin C,Lee JY,Huh JB,Shin SW, Risk assessment for clinical attachment loss of periodontal tissue in Korean adults. The journal of advanced prosthodontics. 2011 Mar;     [PubMed PMID: 21503190]

[24]

Borgnakke WS, Does Treatment of Periodontal Disease Influence Systemic Disease? Dental clinics of North America. 2015 Oct;     [PubMed PMID: 26427573]

[25]

Kim J,Amar S, Periodontal disease and systemic conditions: a bidirectional relationship. Odontology. 2006 Sep;     [PubMed PMID: 16998613]

[26]

Nualart Grollmus ZC,Morales Chávez MC,Silvestre Donat FJ, Periodontal disease associated to systemic genetic disorders. Medicina oral, patologia oral y cirugia bucal. 2007 May 1;     [PubMed PMID: 17468717]

[27]

Borrell LN,Beck JD,Heiss G, Socioeconomic disadvantage and periodontal disease: the Dental Atherosclerosis Risk in Communities study. American journal of public health. 2006 Feb;     [PubMed PMID: 16380570]

[28]

Smalley JW, Pathogenic mechanisms in periodontal disease. Advances in dental research. 1994 Jul;     [PubMed PMID: 7865093]

[29]

Eggert FM,McLeod MH,Flowerdew G, Effects of smoking and treatment status on periodontal bacteria: evidence that smoking influences control of periodontal bacteria at the mucosal surface of the gingival crevice. Journal of periodontology. 2001 Sep;     [PubMed PMID: 11577953]

[30]

Cekici A,Kantarci A,Hasturk H,Van Dyke TE, Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontology 2000. 2014 Feb     [PubMed PMID: 24320956]

[31]

Kang W,Hu Z,Ge S, Healthy and Inflamed Gingival Fibroblasts Differ in Their Inflammatory Response to Porphyromonas gingivalis Lipopolysaccharide. Inflammation. 2016 Oct     [PubMed PMID: 27525424]

[32]

Wiebe CB,Putnins EE, The periodontal disease classification system of the American Academy of Periodontology--an update. Journal (Canadian Dental Association). 2000 Dec;     [PubMed PMID: 11253351]

[33]

Mehrotra N,Singh S, Periodontitis . 2020 Jan     [PubMed PMID: 31082170]

[34]

Haber J,Kent RL, Cigarette smoking in a periodontal practice. Journal of periodontology. 1992 Feb;     [PubMed PMID: 1552463]

[35]

Haber J, Cigarette smoking: a major risk factor for periodontitis. Compendium (Newtown, Pa.). 1994 Aug;     [PubMed PMID: 7987894]

[36]

Costa FO,Miranda Cota LO,Pereira Lages EJ,Soares Dutra Oliveira AM,Dutra Oliveira PA,Cyrino RM,Medeiros Lorentz TC,Cortelli SC,Cortelli JR, Progression of periodontitis and tooth loss associated with glycemic control in individuals undergoing periodontal maintenance therapy: a 5-year follow-up study. Journal of periodontology. 2013 May;     [PubMed PMID: 22769441]

[37]

Pietruska M,Paniczko A,Waszkiel D,Pietruski J,Bernaczyk A, Efficacy of local treatment with chlorhexidine gluconate drugs on the clinical status of periodontium in chronic periodontitis patients. Advances in medical sciences. 2006;     [PubMed PMID: 17458083]

[38]

Kumar AJ,Ramesh Reddy BV,Chava VK, Effect of chlorhexidine chip in the treatment of chronic periodontitis. Journal of natural science, biology, and medicine. 2014 Jul;     [PubMed PMID: 25097396]

[39]

Jhinger N,Kapoor D,Jain R, Comparison of Periochip (chlorhexidine gluconate 2.5 mg) and Arestin (Minocycline hydrochloride 1 mg) in the management of chronic periodontitis. Indian journal of dentistry. 2015 Jan-Mar;     [PubMed PMID: 25767356]

[40]

Lu HK,Chei CJ, Efficacy of subgingivally applied minocycline in the treatment of chronic periodontitis. Journal of periodontal research. 2005 Feb;     [PubMed PMID: 15613075]

[41]

Blair FM,Chapple IL, Prescribing for periodontal disease. Primary dental journal. 2014 Nov;     [PubMed PMID: 25668374]

[42]

LeszczyƄska A,Buczko P,Buczko W,Pietruska M, Periodontal pharmacotherapy - an updated review. Advances in medical sciences. 2011;     [PubMed PMID: 22112427]

[43]

Barca E,Cifcibasi E,Cintan S, Adjunctive use of antibiotics in periodontal therapy. Journal of Istanbul University Faculty of Dentistry. 2015;     [PubMed PMID: 28955547]

[44]

Singh P, Endo-perio dilemma: a brief review. Dental research journal. 2011 Winter;     [PubMed PMID: 22132014]

[45]

Al-Fouzan KS, A new classification of endodontic-periodontal lesions. International journal of dentistry. 2014;     [PubMed PMID: 24829580]

[46]

Herrera D,Alonso B,de Arriba L,Santa Cruz I,Serrano C,Sanz M, Acute periodontal lesions. Periodontology 2000. 2014 Jun;     [PubMed PMID: 24738591]

[47]

Lim HC,Kim CS, Oral signs of acute leukemia for early detection. Journal of periodontal     [PubMed PMID: 25568810]

[48]

Nyska A,Shemesh M,Tal H,Dayan D, Gingival hyperplasia induced by calcium channel blockers: mode of action. Medical hypotheses. 1994 Aug;     [PubMed PMID: 7990738]

[49]

Umeizudike KA,Olawuyi AB,Umeizudike TI,Olusegun-Joseph AD,Bello BT, Effect of Calcium Channel Blockers on Gingival Tissues in Hypertensive Patients in Lagos, Nigeria: A Pilot Study. Contemporary clinical dentistry. 2017 Oct-Dec;     [PubMed PMID: 29326507]

[50]

Bornstein MM,Andreoni C,Meier T,Leung YY, Squamous Cell Carcinoma of the Gingiva Mimicking Periodontal Disease: A Diagnostic Challenge and Therapeutic Dilemma. The International journal of periodontics     [PubMed PMID: 29447319]

[51]

Gupta R,Debnath N,Nayak PA,Khandelwal V, Gingival squamous cell carcinoma presenting as periodontal lesion in the mandibular posterior region. BMJ case reports. 2014 Aug 19;     [PubMed PMID: 25139914]

[52]

Papapanou PN,Sanz M,Buduneli N,Dietrich T,Feres M,Fine DH,Flemmig TF,Garcia R,Giannobile WV,Graziani F,Greenwell H,Herrera D,Kao RT,Kebschull M,Kinane DF,Kirkwood KL,Kocher T,Kornman KS,Kumar PS,Loos BG,Machtei E,Meng H,Mombelli A,Needleman I,Offenbacher S,Seymour GJ,Teles R,Tonetti MS, Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. Journal of periodontology. 2018 Jun;     [PubMed PMID: 29926951]

[53]

Martinez-Canut P,Llobell A, A comprehensive approach to assigning periodontal prognosis. Journal of clinical periodontology. 2018 Apr;     [PubMed PMID: 29247450]

[54]

Ioannou AL,Kotsakis GA,Hinrichs JE, Prognostic factors in periodontal therapy and their association with treatment outcomes. World journal of clinical cases. 2014 Dec 16;     [PubMed PMID: 25516855]

[55]

Mawardi HH,Elbadawi LS,Sonis ST, Current understanding of the relationship between periodontal and systemic diseases. Saudi medical journal. 2015 Feb;     [PubMed PMID: 25719577]

[56]

Kidambi S,Patel SB, Diabetes mellitus: considerations for dentistry. Journal of the American Dental Association (1939). 2008 Oct;     [PubMed PMID: 18809649]

[57]

Kumar M,Mishra L,Mohanty R,Nayak R,     [PubMed PMID: 25450824]

[58]

Ship JA, Diabetes and oral health: an overview. Journal of the American Dental Association (1939). 2003 Oct;     [PubMed PMID: 18196667]

[59]

Kodovazenitis G,Pitsavos C,Papadimitriou L,Deliargyris EN,Vrotsos I,Stefanadis C,Madianos PN, Periodontal disease is associated with higher levels of C-reactive protein in non-diabetic, non-smoking acute myocardial infarction patients. Journal of dentistry. 2011 Dec;     [PubMed PMID: 21946158]

[60]

Desvarieux M,Demmer RT,Rundek T,Boden-Albala B,Jacobs DR Jr,Sacco RL,Papapanou PN, Periodontal microbiota and carotid intima-media thickness: the Oral Infections and Vascular Disease Epidemiology Study (INVEST). Circulation. 2005 Feb 8;     [PubMed PMID: 15699278]

[61]

Joshipura K,Ritchie C,Douglass C, Strength of evidence linking oral conditions and systemic disease. Compendium of continuing education in dentistry. (Jamesburg, N.J. : 1995). Supplement. 2000;     [PubMed PMID: 11908384]

[62]

Schure R,Costa KD,Rezaei R,Lee W,Laschinger C,Tenenbaum HC,McCulloch CA, Impact of matrix metalloproteinases on inhibition of mineralization by fetuin. Journal of periodontal research. 2013 Jun     [PubMed PMID: 23058002]

[63]

López NJ,Da Silva I,Ipinza J,Gutiérrez J, Periodontal Therapy Reduces the Rate of Preterm Low Birth Weight in Women With Pregnancy-Associated Gingivitis. Journal of periodontology. 2005 Nov;     [PubMed PMID: 29539053]

[64]

Offenbacher S,Lin D,Strauss R,McKaig R,Irving J,Barros SP,Moss K,Barrow DA,Hefti A,Beck JD, Effects of periodontal therapy during pregnancy on periodontal status, biologic parameters, and pregnancy outcomes: a pilot study. Journal of periodontology. 2006 Dec;     [PubMed PMID: 17209786]

[65]

Piscoya MD,Ximenes RA,Silva GM,Jamelli SR,Coutinho SB, Periodontitis-associated risk factors in pregnant women. Clinics (Sao Paulo, Brazil). 2012;     [PubMed PMID: 22249477]

[66]

Offenbacher S,Boggess KA,Murtha AP,Jared HL,Lieff S,McKaig RG,Mauriello SM,Moss KL,Beck JD, Progressive periodontal disease and risk of very preterm delivery. Obstetrics and gynecology. 2006 Jan;     [PubMed PMID: 16394036]

[67]

Turton M,Africa CWJ, Further evidence for periodontal disease as a risk indicator for adverse pregnancy outcomes. International dental journal. 2017 Jun;     [PubMed PMID: 27988930]