Matthew P. Lungren Michael R.B. Evans Editors Biomarkers in Clinical Medicine Periodontal Health Covertemplate and Disease RSuatbitointlael efo, rB enefits, and Future DCliirneicctaiol Mnsedicine Covers T3_HB NSeucrocnadn EBduitdiuonneli 112323 Biomarkers in Periodontal Health and Disease Nurcan Buduneli Biomarkers in Periodontal Health and Disease Rationale, Benefits, and Future Directions Nurcan Buduneli Department of Periodontology Faculty of Dentistry Ege University Izmir, Turkey ISBN 978-3-030-37315-3 ISBN 978-3-030-37317-7 (eBook) https://doi.org/10.1007/978-3-030-37317-7 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland The supreme guide in life is science. Do not be afraid of telling the truth. Mustafa Kemal ATATÜRK Dedicated to mom, who has always been the major encouraging power behind me; to dad, who had always believed in me And to my dear daughter and son, who are my hope for the future Preface Periodontal diseases continue to be one of the most common chronic infec- tious and inflammatory diseases in the world. Pathogenic mechanisms acting in periodontal diseases contain two major arms: the microbial component and the host response. Knowledge on both aspects has been increasing tremen- dously during the last two decades. Indeed, the progress in knowledge and the available evidence have led European Federation of Periodontology and American Academy of Periodontology to combine power and build up a new classification system for periodontal diseases in 2017 after 18 years passed since the 1999 Classification. Periodontology is one of the most glamorous fields of dentistry with doz- ens of exciting papers, which open up completely novel pathways of research. “The more we understand the scenario the more complex it becomes.” This is quite true for periodontology. However, this complexity not only attracts even more scientists to work in this field but also stimulates building new bridges between various disciplines of dentistry and medicine to make the story clear. Development of chair-side diagnostic tests for determining the presence or absence of periodontal disease and activity is still a challenge in periodontol- ogy. The use of biofluid samples such as gingival crevicular fluid, whole saliva, and serum as a means of evaluating host-derived products, as well as exogenous components has a great potential for diagnosis and monitorisation of periodontal diseases. Having more precise and early diagnostic tools may enable early intervention and help to develop individually tailored treatment modalities. We are not there, yet, but shall expect to arrive soon. The techno- logical developments in laboratory methods and the closer collaboration with different branches of medicine bring great hope for the future. The spirit of positivity with “can do” and “will do” is definitely encouraging; however, it is clear that reliable biomarkers should base on strong evidence. I hope this monograph will help to fire more researchers working in the field of peri- odontology to get involved. Moonlight floods the whole sky from horizon to horizon How much it can fill your room depends on its windows. Mawlana Jalal-al-Din Rumi İzmir, Anatolia Nurcan Buduneli September 2019 ix Acknowledgements I am grateful to Dr. Burcu Kanmaz for kindly preparing all the illustrations and providing the photographs for this book. xi Contents 1 Anatomy of Periodontal Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 Healthy Periodontal Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1.1 Gingiva . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1.2 Dentogingival Junction . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.1.3 Cementum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.1.4 Periodontal Ligament . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.1.5 Alveolar Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.2 Blood Supply of the Periodontium . . . . . . . . . . . . . . . . . . . . . . 6 1.3 Lymphatic System of the Periodontium . . . . . . . . . . . . . . . . . . . 6 1.4 Nerves of the Periodontium . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.5 Stem Cells of the Periodontium . . . . . . . . . . . . . . . . . . . . . . . . . 6 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2 Nature of Periodontal Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.1 Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.2 Pathogen Microorganisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2.3 Immune Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.4 Osteoclastic Bone Resorption . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2.5 Network of Cytokines and Chemokines . . . . . . . . . . . . . . . . . . 15 2.6 Lipid Mediators of Inflammation . . . . . . . . . . . . . . . . . . . . . . . . 16 2.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3 Conventional Diagnosis of Periodontal Diseases and the 2017 Classification System . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1 1989 Classification of Periodontal Diseases . . . . . . . . . . . . . . . 21 3.2 1999 Classification of Periodontal Disease . . . . . . . . . . . . . . . . 22 3.3 2017 Classification of Periodontal Diseases . . . . . . . . . . . . . . . 22 3.4 Medical and Dental History . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 3.5 Clinical Periodontal Parameters . . . . . . . . . . . . . . . . . . . . . . . . . 26 3.5.1 Bleeding on Probing . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3.5.2 Suppuration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3.5.3 Clinical Attachment Level . . . . . . . . . . . . . . . . . . . . . . . 30 3.5.4 Relative Attachment Level . . . . . . . . . . . . . . . . . . . . . . . 30 3.5.5 Probing Depth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 3.5.6 Gingival Recession . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3.5.7 Furcation Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3.5.8 Pathologic Tooth Migration . . . . . . . . . . . . . . . . . . . . . . 31 xiii xiv Contents 3.5.9 Increased Tooth Mobility . . . . . . . . . . . . . . . . . . . . . . . . 31 3.5.10 Bone Sounding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 3.5.11 Oral Hygiene Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 3.6 Radiographical Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 3.7 Limitations of the Conventional Diagnostic Methods . . . . . . . . 33 3.8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 4 Novel Diagnostic Approaches in Periodontics . . . . . . . . . . . . . . . . 35 4.1 Controlled-Force, Standardised Probes . . . . . . . . . . . . . . . . . . . 36 4.2 Voice-Activated Charting System . . . . . . . . . . . . . . . . . . . . . . . 36 4.3 Advanced Techniques with 3-Dimensional Imaging . . . . . . . . . 36 4.4 Computer-Assisted Digital Radiography . . . . . . . . . . . . . . . . . . 37 4.5 Computer-Assisted Densitometric Image Analysis (CADIA) . . 37 4.6 Cone-Beam Computerised Tomography . . . . . . . . . . . . . . . . . . 37 4.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 5 Biomarkers for Periodontal Diseases . . . . . . . . . . . . . . . . . . . . . . . 41 5.1 Main Text . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 5.1.1 How to Find a Needle in the Haystack? . . . . . . . . . . . . . 41 5.2 Microbial Factors for the Diagnosis of Periodontal Diseases . . 42 5.3 Biomarkers for Detection of Periodontal Disease . . . . . . . . . . . 43 5.4 Biomarkers for Prognosis of Non-surgical Periodontal Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 5.5 Biomarkers for Monitoring of Disease Progress . . . . . . . . . . . . 50 5.5.1 Response to Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . 50 5.6 Point-of-Care Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 5.7 Limitations of Available Studies . . . . . . . . . . . . . . . . . . . . . . . . 53 5.8 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 6 Biological Samples for Biomarkers: Strengths and Weaknesses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 6.1 Saliva . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 6.1.1 Collection of Saliva Samples . . . . . . . . . . . . . . . . . . . . . 60 6.1.2 Content of Saliva . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 6.1.3 Functions of Saliva . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 6.2 Gingival Crevicular Fluid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 6.2.1 Methods of Collection . . . . . . . . . . . . . . . . . . . . . . . . . . 63 6.2.2 Reporting GCF Sample Volume and Biomarker Data . . . 65 6.3 Serum or Plasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 6.4 Gingival Tissue Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 6.5 Calcified Tissue Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 6.6 Plaque . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 6.7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 7 Technologies for Biomarkers in Periodontics . . . . . . . . . . . . . . . . . 69 7.1 Biochemical Analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69