Mechanical debridement with antibiotics in the treatment of chronic periodontitis : effect on systemic biomarkers : a systematic review

Munasur, Sudhir L. (2019-04)

Thesis (MMed)--Stellenbosch University, 2019.

Thesis

ENGLISH SUMMARY : Background: Chronic periodontitis is an inflammatory oral disease which leads to the destruction of the supporting tissues of the teeth, leading to bone resorption and tooth loss. Destruction of the periodontal attachment apparatus can result in gingival recession and root furcation exposure in advanced stages resulting in tooth mobility and tooth loss. Mechanical debridement is the most frequent treatment for chronic periodontitis, in severe cases systemic antibiotics in conjunction with mechanical debridement have been used. The efficacy and the beneficial effect of this combination on the inflammatory biomarkers require further investigation. Objectives: The aim of this systematic review was to assess the effectiveness of adjunctive antibiotics in the improvement of inflammatory systemic biomarkers in the treatment chronic periodontitis. Search methods: We searched the following electronic databases: Cochrane Oral Health Group Trials Register (30th June 2018). The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2018 – current issue), MEDLINE (1966 to present), EMBASE (1982 to present), CINAHL via EBSCO (1990 -present), Google scholar (1990 - present). Web of Knowledge (1990 to May 2018), The meta-Register of Controlled Trials (www.controlled-trials.com), The US National Institutes of Health On-going Trials Register (www.clinicaltrials.gov). The World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch) was searched to identify relevant trials for inclusion in the review. Conference proceedings, on-going trials registers (02/06/2018) and reference list of included articles were assessed for relevant trials. No language or date of publication restrictions applied. Selection criteria: We searched for randomised controlled trials (RCTs that evaluated the effectiveness of adjunct antibiotic therapy on the systemic biomarkers in the treatment of chronic periodontitis. All trials that compared adjunctive systemic antibiotics with mechanical debridement or mechanical debridement alone, or scaling and root planning, oral hygiene and prophylaxis or placebo were included in the study. Data collection and analysis: Two reviewers independently examined the titles and abstracts retrieved by the search to identify relevant trials for inclusion in the review. All included trials were assessed for risk of bias and data were extracted for further analysis. The primary outcomes assessed include: changes in serum/blood levels of inflammatory biomarkers such as Matrix Metalloproteinases (MMPs), Tissue Inhibitors of MMPs(TIMs), Cytokines, C-Reactive Protein(CRP) and Glycated haemoglobin(HbA1c). Secondary outcomes include periodontal indices such as bleeding on probing (BOP), gingival index (GI), clinical attachment level (CAL), plaque index (PI) and probing pocket depth (PPD). Main results: Fourteen trials (n=1457 participants) were included in the review. Seven trials reported on MMP-8, with average of 3 months time to event. Five trials reported on IL-1β, three trials on IL-6 and two on IL-8 serum level. Four trials reported on CRP; while eight reported on HbA1c level and one on TIMP-1 level. Trials were assessed for risk of bias and judged as low, high, or unclear of risk of bias. Six studies showed no significant differences in MMP-8 concentration level between the two intervention groups. Significant decrease (60%) in odds of increased MMP-8 levels during 2-year study was reported in one trial (OR 0.40, 95%CI: 0.21 to 0.77, p=0.006). One study reported no significant difference for TIMP-1 (0.96, 95% CI: 0.78 to 1.18, p=0.7), while two studies showed significant reduction in HbA1c (10%) at 3 months. Other studies reported no difference in HbA1c levels (%): (Mean (SD) 7.00 (0.76) versus 7.11 (0.99); p=0.710), (Median (Interquartile Range [IQR]) 6.3 (5.5,7.3) versus 6.7 (6.3, 7.7); p=0.8), (p=0.35, 0.55, 0.33, and 0.62, at baseline, 3 months, 6 months, and after 1 year of treatment respectively. Metaanalysis showed a mean reduction of 0.24mm in the periodontal pockets (PD) at 3 months [MD, -0.25 with 95% CI -0.38 to -0.12]. Two trials revealed no significant difference PD≤3mm at 3 months, [MD, -1, 95% CI -22.54 to 20.53 (p=0.19)]. A decrease in periodontal pockets(PD≥4mm) and a reduction of 3.38mm in favour of SRP+antibiotics after 3 months [MD, -3.38, 95% CI -6.51 to -0.25 (p=0.93, I2=0%)] was observed for probing depth(PD). No significant difference in clinical attachment level (CAL) at 3 months [MD, -0.13, 95% CI -0.34 to 0.07; Chi2=0.98, df=3, p=0.81, I2=0%]. The overall quality of evidence was low largely because of attrition bias (24%; 32%) connoting high risk of bias and wide confidence intervals which suggests imprecision of results. Authors' conclusions: There is limited but low-level of evidence suggesting that systemic antibiotic therapy combined with mechanical debridement improves the systemic biomarker levels during the treatment of chronic periodontitis.

AFRIKAANSE OPSOMMING : Agtergrond: Chroniese periodontitis is ‘n inflammatoriese mondsiekte wat lei tot die vernietiging van die ondersteunende weefsel van die tande, en uiteindelik tot beenresorpsie en tandverlies. Vernietiging van die periodontale hegtingsorgane kan lei tot tandvleis-terugsakking en wortelaftakking-ontbloting en, in meer gevorderde stadiums, potensieel tot tandmobiliteits- en tandverlies. Tandsteenverwydering en wortelbeplanning, ook bekend as meganiese brokstukverwydering, is die behandeling wat die meeste op chroniese periodontitis toegepas word. Vir ernstige gevalle van periodontale siektes, is sistemiese antibiotika tesame met skalering en wortelbeplanning gebruik; die doeltreffendheid hierdie kombinasie benodig verdere ondersoek oor die voordelige uitwerking op die vlak van inflammatoriese biomerkers. Doelwitte: Die doel van hierdie sistematiese oorsig was om die effektiwiteit van adjunktiewe (bykomende) antibiotika in die verbetering van inflammatoriese sistemiese biomerkers in die behandeling van chroniese periodontitis te assesseer. Soekmetodes: Ons het deur die volgende elektroniese databasisse gesoek: Cochrane Oral Health Group Trials Register (30 Junie 2018), The Cochrane Central Register of Controlled Trials (Trials (CENTRAL) (Cochrane Library 2018 – jongste uitgawe), MEDLINE (1966 tot hede), EMBASE (1982 tot hede), CINAHL via EBSCO (1990 – hede), Google scholar (1990 – hede). Web of Knowledge (1990 tot Mei 2018), The meta-Register of Controlled Trials (www.controlledtrials. com), The US National Institutes of Health On-going Trials Register (www.clinicaltrials.gov). The World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch) is ondersoek om relevante proefnemings vir insluiting in die oorsig te identifiseer. Relevante konferensieprosedures, deurlopende proefnemingsregisters (02/06/2018) en verwysingslyste van ingeslote artikels is vir relevante proefnemings geassesseer. Geen beperkings is geplaas op die taal of datum van publikasie toe die elektroniese databasisse ondersoek is nie. Seleksiekriteria: Ons het gesoek na lukraak gekontroleerde proefnemings (RCT’s) wat die effektiwiteit van adjunkte antibiotiese terapie op die sistemiese biomerkers in die behandeling van chroniese periodontitis geëvalueer het. Alle geïdentifiseerde RCT’s wat adjunktiewe sistemiese antibiotika met meganiese verwydering alleen of met skalering en wortelbeplanning, mondhigiëne en profilakse of plasebo vergelyk, is in die studie ingesluit. Dataversameling en -analise: Twee ondersoekende outeurs het onafhanklik van mekaar die titels en abstrakte bestudeer wat deur die soektog opgespoor is om die ingeslote proefnemings te selekteer. Elke ingeslote soektog is geassesseer vir risiko van vooroordeel (Sien risiko van vooroordeel-tabel) en relevante data is vir verdere analise onttrek. Ons primêr geassesseerde uitkomste is: veranderings in serum/bloedvlakke van inflammatoriese biomerkers soos (Matrix Metalloproteinases) MMPs, (Tissue Inhibitors of MMPs) TIMs, Cytokines, C-Reactive Protein(CRP) en Glycated haemoglobin (HbA1c). Sekondêre uitkomste sluit in periodontale aanduiders soos bloeding by ondersoek (BOP), tandvleis-indeks (GI), kliniese aanhegtingsvlak (CAL), plaak-indeks (PI) en diepte van ondersoek (PPD). Belangrikste resultate: Veertien proefnemings (n=1457) is in die ondersoek ingesluit. Alle proefnemings het antibiotika versus plasebo gekombineer met meganiese verwydering vergelyk. Sewe proefnemings het MMP-8 gerapporteer, met ‘n gemiddelde van 3 maande tot ryd van uitslag. Vyf proefnemings op IL-β, drie proefnemings op IL-6 en twee op IL-8 serumvlak. Daar is vier proefnemings op CRP gerapporteer; agt op HbA1c vlak en een op TIMP-1 vlak. Proefnemings is geassesseer vir risiko van partydigheid en geoordeel as synde laag, hoog, of onduidelik weens risiko van strydigheid. Ses studies het geen noemenswaardige verskille in MMP-8 konsentrasievlak tussen twee intervensiegroepe aangetoon nie. ‘n Aansienlike afname (60%) in verskille van verhoogde MMP-8 vlakke gedurende ‘n 2-jaarstudie is in een ondersoek (OR 0.40, 95%CI: 0.21 tot0.77, p=0.006) gerapporteer. Een studie het gewys op een nie-opvallende verskil vir TIMP-1 (0.96, 95% CI: 0.78 tot 1.18, p=0.7). Slegs twee studies het aansienlike verlaging in HbA1c (10% verlaging op 3 maande) aangetoon, terwyl ander geen opvallende verskil in HbA1c-vlakke aangetoon het nie (%): (Gemiddelde (SD) 7.00 (0.76) versus 7.11 (0.99); p=0.710), (Mediaan (Interkwartiel-omvang [IQR]) 6.3 (5.5,7.3) versus 6.7 (6.3 7.7); p=0.8), (p=0.35, 0.55, 0.33, en 0.62, op 3 maande, 6 maande, en ná 1 jaar van behandeling onderskeidelik. ‘n Studie het na 3 maande (1.5%) versus (0.9%) aangetoon; geen aansienlike verskil op 3 maande nie (p=0.22). Meta-analise vertoon ‘n gemiddelde verlaging van 0.24mm in die periodontale sakke (PD) op 3 maande [MD, -0.25 met 95% CI -0.38 tot -0.12], terwyl twee proefnemings geen beduidende verskil PD≤3mm op 3 maande, [MD, -1 met 95% CI -22.54 tot 20.53 (p=0.19)] aangetoon het nie. ‘n Afname in periodontale sakke (PD≥4mm) en ‘n verlaging van 3.38mm ten gunste van die SRP + antibiotika na 3 maande [MD, -3.38 met 95% CI -6.51 tot -0.25 (p=0.93; I2=0%)])] is vir ondersoekdiepte (PD) waargeneem. Geen aansienlike verskil in kliniese hegtingsvlak (CAL) op 3 maande [MD, -0.13 op 95% CI -0.34 tot 0.07; Chi2=0.98, df=3, p=0.81, I2=0%]. Gehalte van bewys is geassesseer deur GRADEpro en het lae voorkoms van effektiwiteit van adjunkte sistemiese antibiotika in die behandeling van chroniese periodontitis aangetoon. Skrywers se gevolgtrekkings: Daar is beperkte maar laevlak-bewyse wat suggereer dat sistemiese antibiotiese terapie gekombineer met meganiese verbrokkeling die sistemiese biomerkervlakke gedurende die behandeling van chroniese periodontitis verbeter.

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