Comorbidity of periodontal disease: two sides of the same coin? An introduction for the clinician

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ABSTRACT

Increasing evidence has suggested an independent association between periodontitis and a range of comorbidities, for example cardiovascular disease, type 2 diabetes, rheumatoid arthritis, osteoporosis, Parkinson’s disease, Alzheimer’s disease, psoriasis, and respiratory infections. Shared inflammatory pathways are likely to contribute to this association, but distinct causal mechanisms remain to be defined. Some of these comorbid conditions may improve by periodontal treatment, and a bidirectional relationship may exist, where, for example, treatment of diabetes can improve periodontal status. The present article presents an overview of the evidence linking periodontitis with selected systemic diseases and calls for increased cooperation between dentists and medical doctors to provide optimal screening, treatment, and prevention of both periodontitis and its comorbidities.

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Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

E H Corder, A M Saunders, W J Strittmatter … (1993)

The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.

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From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis.

Stavros C. Manolagas (2010)

Estrogen deficiency has been considered the seminal mechanism of osteoporosis in both women and men, but epidemiological evidence in humans and recent mechanistic studies in rodents indicate that aging and the associated increase in reactive oxygen species (ROS) are the proximal culprits. ROS greatly influence the generation and survival of osteoclasts, osteoblasts, and osteocytes. Moreover, oxidative defense by the FoxO transcription factors is indispensable for skeletal homeostasis at any age. Loss of estrogens or androgens decreases defense against oxidative stress in bone, and this accounts for the increased bone resorption associated with the acute loss of these hormones. ROS-activated FoxOs in early mesenchymal progenitors also divert ss-catenin away from Wnt signaling, leading to decreased osteoblastogenesis. This latter mechanism may be implicated in the pathogenesis of type 1 and 2 diabetes and ROS-mediated adverse effects of diabetes on bone formation. Attenuation of Wnt signaling by the activation of peroxisome proliferator-activated receptor gamma by ligands generated from lipid oxidation also contributes to the age-dependent decrease in bone formation, suggesting a mechanistic explanation for the link between atherosclerosis and osteoporosis. Additionally, increased glucocorticoid production and sensitivity with advancing age decrease skeletal hydration and thereby increase skeletal fragility by attenuating the volume of the bone vasculature and interstitial fluid. This emerging evidence provides a paradigm shift from the "estrogen-centric" account of the pathogenesis of involutional osteoporosis to one in which age-related mechanisms intrinsic to bone and oxidative stress are protagonists and age-related changes in other organs and tissues, such as ovaries, accentuate them.

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Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.

G Schellekens, B. de Jong, F van den Hoogen … (1998)

Only a few autoantibodies that are more or less specific for RA have been described so far. The rheumatoid factor most often tested for is not very specific for RA, while the more specific antiperinuclear factor for several reasons is not routinely used as a serological parameter. Here we show that autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline, a posttranslationally modified arginine residue, are specifically present in the sera of RA patients. Using several citrulline-containing peptide variants in ELISA, antibodies could be detected in 76% of RA sera with a specificity of 96%. Sera showed a remarkable variety in the reactivity pattern towards different citrulline-containing peptides. Affinity-purified antibodies were shown to be positive in the immunofluorescence-based antiperinuclear factor test, and in the so-called antikeratin antibody test, and were reactive towards filaggrin extracted from human epidermis. The specific nature of these antibodies and the presence of these antibodies early in disease, even before other disease manifestations occur, are indicative for a possible role of citrulline-containing epitopes in the pathogenesis of RA.

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Author and article information

Journal

Journal ID (nlm-ta): J Oral Microbiol

Journal ID (iso-abbrev): J Oral Microbiol

Journal ID (archive): ZJOM

Journal ID (publisher-id): zjom20

Title: Journal of Oral Microbiology

Publisher: Taylor & Francis

ISSN (Electronic): 2000-2297

Publication date Collection: 2017

Publication date (Electronic): 14 June 2017

Volume: 9

Issue: 1

Electronic Location Identifier: 1332710

Affiliations

[ ^a ] Section for Periodontology, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark

[ ^b ] Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen University Hospital , Copenhagen, Denmark

[ ^c ] Department of Oral Biology, Faculty of Dentistry, University of Oslo , Oslo, Norway

[ ^d ] Department of Periodontology, Faculty of Odontology, Malmö University , Malmö, Sweden

[ ^e ] Division of Periodontology, Department of Dental Medicine, Karolinska Institutet , Stockholm, Sweden

[ ^f ] Steno Diabetes Center Copenhagen , Copenhagen, Denmark

[ ^g ] Cardiology Department, Herlev and Gentofte Hospital , Hellerup, Denmark

Author notes

CONTACT Palle Holmstrup pah@ 123456sund.ku.dk

Article

Publisher ID: 1332710

DOI: 10.1080/20002297.2017.1332710

PMC ID: 5508374

PubMed ID: 28748036

SO-VID: 908b150f-5aa6-40fa-8f3b-02575b9f9aa1

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 27 October 2016

Date accepted : 7 January 2017

Page count

Tables: 2, References: 126, Pages: 14

Funding

This work was supported by the European Commission [FP7-HEALTH-306029], Danish Dental Association, Danish Foundation for Mutual Efforts in Dental Care, and Simon Spies Foundation.

Comorbidity of periodontal disease: two sides of the same coin? An introduction for the clinician

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Most cited references 92

Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis.

Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies.

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