Volkan ARIKAN, Nimet Gül GÖRGÜLÜ, Başak DOĞAN

Clinical and Biochemical Effects of Smoking on Non-Surgical Periodontal Treatment in Grade III Stage C Periodontitis Patients

Objective: The purpose of this study was to evaluate the effect of smoking on clinical parameters and the serum and saliva levels of RANKL, OPG, and IL-34 in periodontitis stage III grade C (III-C) patients after non-surgical periodontal treatment (NSPT). Methods: A total of 60 subjects, 40 periodontitis-III-C patients (20 smokers and 20 non-smokers) and 20 non-smoker periodontally healthy individuals, were included. All clinical periodontal parameters were recorded, and unstimulated saliva and serum samples were collected from all patients at baseline, but at 1 and 3 months only from periodontitis patients (N=40). Saliva and serum levels of RANKL, OPG, and IL-34 were analyzed by ELISA. Results: At baseline only whole mouth probing depth (PD) and percent of sites with PD>5mm were higher in smokers than non-smoker periodontitis patients (p<.05). All periodontal measurements significantly improved in both periodontitis groups after NSPT (p<.001). After NSPT, the reduction in gingival index (GI), bleeding on probing (BOP), and mean PD in sites initially PD≥5mm were lower in smokers than nonsmoker periodontitis patients (p>.05). Only saliva IL-34 levels were higher in all-periodontitis patients than healthy individuals (p=.001) and decreased in both periodontitis groups after NSPT (p<.05). Moreover, elevated serum RANKL level was detected in smokers compared to nonsmoker periodontitis or healthy ones at baseline (p<.05). Serum RANKL levels exhibited no change after NSPT in either periodontitis groups. Conclusions: The smokers are less responsive to NSPT, and saliva IL-34 can be a potential inflammatory marker of periodontitis-III-C. Moreover, high serum RANKL levels are associated with smoking.

Keywords:

periodontitis, smoking interleukin-34, receptor activator of nuclear factor-kappa B ligand, osteoprotegerin,

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Apatzidou D, Riggio M, Kinane D. Impact of smoking on the clinical, microbiological and immunological parameters of adult patients with periodontitis. J Clin Periodontol. 2005;32(9):973-983. DOI: 10.1111/j.1600-051X.2005.00788.x
Johnson GK, Guthmiller JM. The impact of cigarette smoking on periodontal disease and treatment. Periodontol 2000. 2007;44(1):178-194. DOI: 10.1111/j.1600-0757.2007.00212.x
Helal O, Göstemeyer G, Krois J, Fawzy El Sayed K, Graetz C, Schwendicke F. Predictors for tooth loss in periodontitis patients: Systematic review and meta‐analysis. J Clin Periodontol. 2019;46(7):699-712. DOI: 10.1111/jcpe.13118
Guru S, Sam SE, Rajan S, Padmanabhan S. Comparative evaluation of salivary hepatocyte growth factor in smokers and non‐smokers with chronic periodontitis. J Investig Clin Dent. 2018;9(2):e12306. DOI: 10.1111/jicd.12306
Preshaw PM, Lauffart B, Zak E, Jeffcoat MK, Barton I, Heasman PA. Progression and treatment of chronic adult periodontitis. J Periodontol. 1999;70(10):1209-1220. DOI: 10.1902/jop.1999.70.10.1209
Preshaw P, Holliday R, Law H, Heasman P. Outcomes of non‐surgical periodontal treatment by dental hygienists in training: impact of site‐and patient‐level factors. Int J Dent Hyg. 2013;11(4):273-279. DOI: 10.1111/idh.12032
Ardais R, Mário Tde G, Boligon J, Kantorski KZ, Moreira CH. The effect of smoking on bleeding on probing after nonsurgical periodontal therapy: a quasi-experimental study. Braz Oral Res. 2014;28:1-7. DOI: 10.1590/1807-3107bor-2014.vol28.0058
Buduneli N, Kardeşler L, Işık H, Willis III CS, Hawkins SI, Kinane DF, Scott DA. Effects of smoking and gingival inflammation on salivary antioxidant capacity. J Clin Periodontol. 2006;33(3):159-164. DOI: 10.1111/j.1600-051X.2006.00892.x
Ojima M, Hanioka T. Destructive effects of smoking on molecular and genetic factors of periodontal disease. Tob Induc Dis. 2010;8(1):1-8. DOI: 10.1186/1617-9625-8-4
Tanaka H, Tanabe N, Shoji M, Suzuki N, Katono T, Sato S, Motohashi M, Maeno M. Nicotine and lipopolysaccharide stimulate the formation of osteoclast-like cells by increasing macrophage colony-stimulating factor and prostaglandin E2 production by osteoblasts. Life Sci. 2006;78(15):1733-1740. DOI: 10.1016/j.lfs.2005.08.017
Linden GJ, Lyons A, Scannapieco FA. Periodontal systemic associations: Review of the evidence. J Periodontol. 2013;84 (Suppl 4):8-19. DOI: 10.1902/jop.2013.1340010.
Kong Y-Y, Yoshida H, Sarosi I, Tan H-L, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397(6717):315-323. DOI: 10.1038/16852
Lacey D, Timms E, Tan H-L, Kelley M, Dunstan C, Burgess T, Elliott R, Colombero A, Elliott G, Scully S. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165-176. DOI: 10.1016/S0092-8674(00)81569-X
Simonet W, Lacey D, Dunstan C, Kelley M, Chang M-S, Lüthy R, Nguyen H, Wooden S, Bennett L, Boone T. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309-319. DOI: 10.1016/S0092-8674(00)80209-3
Özçaka Ö, Nalbantsoy A, Köse T, Buduneli N. Plasma osteoprotegerin levels are decreased in smoker chronic periodontitis patients. Aust Dent J. 2010;55(4):405-410. DOI: 10.1111/j.1834-7819.2010.01261.x
Lappin DF, Sherrabeh S, Jenkins WM, Macpherson LM. Effect of smoking on serum RANKL and OPG in sex, age and clinically matched supportive‐therapy periodontitis patients. J Clin Periodontol. 2007;34(4):271-277. DOI: 10.1111/j.1600-051X.2007.01048.x
Tang TH, Fitzsimmons TR, Bartold PM. Effect of smoking on concentrations of receptor activator of nuclear factor κ B ligand and osteoprotegerin in human gingival crevicular fluid. J Clin Periodontol. 2009;36(9):713-718. DOI: 10.1111/j.1600-051X.2009.01444.x
Buduneli N, Buduneli E, Kütükçüler N. Interleukin‐17, RANKL, and osteoprotegerin levels in gingival crevicular fluid from smoking and non‐smoking patients with chronic periodontitis during initial periodontal treatment. J Clin Periodontol. 2009;80(8):1274-1280. DOI: 10.1902/jop.2009.090106
Behfarnia P, Saied-Moallemi Z, Javanmard SH, Naseri R. Serum, saliva, and GCF concentration of RANKL and osteoprotegerin in smokers versus nonsmokers with chronic periodontitis. Adv Biomed Res. 2016;5:80. DOI: 10.4103/2277-9175.180992.
Yuce HB, Gokturk O, Turkal HA, Inanir A, Benli I, Demir O. Assessment of local and systemic 25-hydroxy-vitamin D, RANKL, OPG, and TNF levels in patients with rheumatoid arthritis and periodontitis. J Oral Sci. 2017;59(3):397-404. DOI: 10.2334/josnusd.16-0677
Doğan SB, Dede FÖ, Balli U, Sertoglu E. Emerging roles of Interleukin-34 together with receptor activator of nuclear factor-kB ligand and osteoprotegerin levels in periodontal disease. Cytokine. 2021;144:155584. DOI: 10.1016/j.cyto.2021.155584
Shetty B, Divakar DD, Al-Kheraif AA, Alharbi AO, Almutairi MST, Alanazi MM. Role of PDT as an adjunct to SRP on whole salivary RANKL and OPG ratio in type-2 diabetic and normoglycemic individuals with chronic periodontitis. Cytokine. 2021;34:102220. DOI: 10.1016/j.pdpdt.2021.102220
Lin H, Lee E, Hestir K, Leo C, Huang M, Bosch E, Halenbeck R, Wu G, Zhou A, Behrens D. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science. 2008;320(5877):807-811. DOI: 10.1126/science.1154370
Guruprasad C, Pradeep A. Influence of smoking on interleukin-34 levels in gingival crevicular fluid and plasma in periodontal health and disease: A clinico-biochemical study. Bull Tokyo Dent Coll. 2018;59(4):247-255. DOI: 10.2209/tdcpublication.2017-0051
Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol. 2018;89(Suppl 1):S159-S172. DOI: 10.1002/jper.18-0006
Lang NP, Bartold PM. Periodontal health. J Periodontol. 2018;89 Suppl 1:S9-s16. DOI: 10.1002/jper.16-0517
Türkoğlu O, Eren G, Emingil G, Azarsız E, Kutukculer N, Atilla G. Does smoking affect gingival crevicular fluid LL-37 levels following non-surgical periodontal treatment in chronic periodontitis? Arch Oral Biol. 2016;61:98-105. DOI: 10.1016/j.archoralbio.2015.10.018
Silness J, Löe H. Periodontal disease in pregnancy II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand. 1964;22(1):121-135. DOI: 10.3109/00016356408993968.
Löe H, Silness J. Periodontal disease in pregnancy I. Prevalence and severity. Acta Odontol Scand. 1963;21(6):533-551. DOI: 10.3109/00016356309011240
Görgülü NG, Doğan B. Effect of non‐surgical periodontal treatment on salivary and serum biomarkers in stage III grade B and C periodontitis. J Periodontol. 2022. DOI: 10.1002/JPER.21-0536
Yamamoto Y, Nishida N, Tanaka M, Hayashi N, Matsuse R, Nakayama K, Morimoto K, Shizukuishi S. Association between passive and active smoking evaluated by salivary cotinine and periodontitis. J Clin Periodontol. 2005;32(10):1041-1046. DOI: 10.1111/j.1600-051X.2005.00819.x
Chen Z, Buki K, Vääräniemi J, Gu G, Väänänen HK. The critical role of IL-34 in osteoclastogenesis. PloS one. 2011;6(4):e18689. DOI: 10.1371/journal.pone.0018689
Yasuda H. Discovery of the RANKL/RANK/OPG system. J Bone Miner Metab. 2021;39(1):2-11. DOI: 10.1007/s00774-020-01175-1
Chang J, Meng HW, Lalla E, Lee CT. The impact of smoking on non-surgical periodontal therapy: A systematic review and meta-analysis. J Clin Periodontol. 2021;48(1):60-75. DOI: 10.1111/jcpe.13384
Tsukasaki M. RANKL and osteoimmunology in periodontitis. J Bone Miner Metab. 2021;39(1):82-90. DOI: 10.1007/s00774-020-01165-3
Frodge BD, Ebersole JL, Kryscio RJ, Thomas MV, Miller CS. Bone remodeling biomarkers of periodontal disease in saliva. J Periodontol. 2008;79(10):1913-1919. DOI: 10.1902/jop.2008.080070
Buduneli N, Bıyıkoğlu B, Sherrabeh S, Lappin DF. Saliva concentrations of RANKL and osteoprotegerin in smoker versus non‐smoker chronic periodontitis patients. J Clin Periodontol. 2008;35(10):846-852. DOI: 10.1111/j.1600-051X.2008.01310.x
Al-Sabbagh M, Alladah A, Lin Y, Kryscio RJ, Thomas MV, Ebersole JL, Miller CS. Bone remodeling-associated salivary biomarker MIP-1α distinguishes periodontal disease from health. J Periodontal Res. 2012;47(3):389-395. DOI: 10.1111/j.1600-0765.2011.01445.x
Caldeira FID, Hidalgo MAR, Dias MLDC, Scarel-Caminaga RM, Pigossi SC. Systematic review of ratios between disease/health periodontitis modulators and meta-analysis of their levels in gingival tissue and biological fluids. Arch Oral Biol. 2021;127:105147. DOI: 10.1016/j.archoralbio.2021.105147
Tabari ZA, Azadmehr A, Tabrizi MAA, Hamissi J, Ghaedi FB. Salivary soluble receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio in periodontal disease and health. J Periodontal Implant Sci. 2013;43(5):227. DOI: 10.5051/jpis.2013.43.5.227
Hikita A, Yana I, Wakeyama H, Nakamura M, Kadono Y, Oshima Y, Nakamura K, Seiki M, Tanaka S. Negative regulation of osteoclastogenesis by ectodomain shedding of receptor activator of NF-kappaB ligand. J Biol Chem. 2006;281(48):36846-36855. DOI: 10.1074/jbc.M606656200
Tsukasaki M, Komatsu N, Nagashima K, Nitta T, Pluemsakunthai W, Shukunami C, Iwakura Y, Nakashima T, Okamoto K, Takayanagi H. Host defense against oral microbiota by bone-damaging T cells. Nat Commun. 2018;9(1):701. DOI: 10.1038/s41467-018-03147-6
Perlstein TS, Lee RT. Smoking, metalloproteinases, and vascular disease. Arterioscler Thromb Vasc Biol. 2006;26(2):250-256. DOI: 10.1161/01.ATV.0000199268.27395.4f
Lum L, Wong BR, Josien R, Becherer JD, Erdjument-Bromage H, Schlöndorff J, Tempst P, Choi Y, Blobel CP. Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival. J Biol Chem. 1999;274(19):13613-13618. DOI: 10.1074/jbc.274.19.13613
Ozçaka O, Biçakci N, Pussinen P, Sorsa T, Köse T, Buduneli N. Smoking and matrix metalloproteinases, neutrophil elastase and myeloperoxidase in chronic periodontitis. Oral Dis. 2011;17(1):68-76. DOI: 10.1111/j.1601-0825.2010.01705.x
He C-Y, Gao X-Q, Jiang L-P. The impact of smoking on levels of chronic periodontitis-associated biomarkers. Exp Mol Pathol. 2016;101(1):110-115. DOI: 10.1016/j.yexmp.2016.07.004
Guruprasad C, Pradeep A. Effect of nonsurgical periodontal therapy on interleukin-34 levels in periodontal health and disease. Indian J Dent Res. 2018;29(3):280-285. DOI: 10.4103/ijdr.IJDR_527_17
Martinez G, Majster M, Bjurshammar N, Johannsen A, Figueredo C, Boström E. Salivary colony stimulating factor‐1 and interleukin‐34 in periodontal disease. J Periodontol. 2017;88(8):e140-e149. DOI: 10.1902/jop.2017.170081
Lira-Junior R, Bissett SM, Preshaw PM, Taylor JJ, Boström EA. Levels of myeloid-related proteins in saliva for screening and monitoring of periodontal disease. J Clin Periodontol. 2021;48(11):1430-1440. DOI: 10.1111/jcpe.13534
Muñoz-Garcia J, Cochonneau D, Télétchéa S, Moranton E, Lanoe D, Brion R, Lézot F, Heymann MF, Heymann D. The twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis. Theranostics. 2021;11(4):1568-1593. DOI: 10.7150/thno.50683