Efficacy of adjunctive periodontal interventions in non-surgical periodontal therapy for Stage III/IV Grade C periodontitis: A systematic review and network meta-analysis

Abstract

This study evaluates the effectiveness of adjunctive therapies combined with non-surgical periodontal treatment for Stage III/IV Grade C periodontitis, focusing on pocket depth (PD) reduction, clinical attachment level (CAL) gain, and adverse events. A systematic review and network meta-analysis were conducted, including randomized controlled trials up to September 2024. Inconsistencies and publication bias were detected, prompting sensitivity analyses and effectiveness rankings of adjunctive therapies. Data from 50 studies were included, with 45 entered into network meta-analysis, covering 24 interventions and 1431 patients. Compared to scaling and root planing (SRP) alone, adjunctive systemic lincosamides with nitroimidazole (Mac/Linc+Nitro-S) demonstrated the greatest PD reduction, followed by local statins (Statins-L) in the short term (≤3 months). Statins-L also provided the highest CAL gain. In the medium term (4-6 months), Statins-L remained the most effective, followed by bisphosphonates. For long-term (>6 months) follow-up, where fewer treatment approaches were available, Nitro-S achieved the most significant PD reduction and CAL gain, followed by Mac/Linc-S. Adverse effects were mild and self-limiting. Despite promising findings, inconsistencies in CAL outcomes and potential publication bias highlight the need for further research to confirm long-term safety and efficacy.

Keywords: Adjunctive periodontal treatment; Aggressive periodontitis; Meta-analysis; Non-surgical periodontal therapy; Stage III/IV Grade C.

Fig. 1

Flow diagram of the study. Abbreviations: GCF, gingival crevicular fluid; n, number; RCT, randomized controlled trial; SRP, scaling and root planing.

Fig. 2

Network plots of treatment comparisons. Network plots displayed treatment comparisons for the change in pocket depth (PD) at (A) short-term, (B) medium-term, and (C) long-term follow-ups, clinical attachment level (CAL) at (D) short-term, (E) medium-term, and (F) long-term follow-ups. The lines connecting nodes indicated direct comparisons between trials, with line thickness reflecting the number of trials involved in the network. The size of each circle corresponds to the number of studies of the respective treatment. Abbreviations: aPDT, antimicrobial photodynamic therapy; BP-L, bisphosphonates-local; CAL, clinical attachment level; CHX, chlorhexidine; Mac/Linc-S, macrolides and lincosamides-systemic; NSAIDS-S, non-steroidal anti-inflammatory drugs-systemic; PD, probing depth; Pen+CA-S, penicillins+clavulanic acid-systemic; Pen+Nitro-S, penicillins+nitroimidazole-systemic; PVP-I, povidone iodine; Quino, quinolones; SRP, scaling and root planing; Tetra-S, tetracyclines-systemic; Tetra-L, tetracyclines-local.

Fig. 3

Cumulative rankograms displayed plots of the surface under the cumulative ranking curves (SUCRAs) for the change in pocket depth (PD) at (A) short-term, (B) medium-term, and (C) long-term follow-ups, clinical attachment level (CAL) at (D) short-term, (E) medium-term, and (F) long-term follow-ups. Ranking in the cumulative rankograms represented the probability of each treatment being the best, second best, and so forth, among the evaluated interventions. A higher SUCRA score indicated a greater effectiveness for a specific intervention. Abbreviations: aPDT, antimicrobial photodynamic therapy; BP-L, bisphosphonates-local; CAL, clinical attachment level; CHX, chlorhexidine; Mac/Linc-S, macrolides and lincosamides-systemic; NSAIDS-S, non-steroidal anti-inflammatory drugs-systemic; PD, probing depth; Pen+CA-S, penicillins+clavulanic acid-systemic; Pen+Nitro-S, penicillins+nitroimidazole-systemic; PVP-I, povidone iodine; Quino, quinolones; SRP, scaling and root planing; Tetra-S, tetracyclines-systemic; Tetra-L, tetracyclines-local.

Fig. 3

Cumulative rankograms displayed plots of the surface under the cumulative ranking curves (SUCRAs) for the change in pocket depth (PD) at (A) short-term, (B) medium-term, and (C) long-term follow-ups, clinical attachment level (CAL) at (D) short-term, (E) medium-term, and (F) long-term follow-ups. Ranking in the cumulative rankograms represented the probability of each treatment being the best, second best, and so forth, among the evaluated interventions. A higher SUCRA score indicated a greater effectiveness for a specific intervention. Abbreviations: aPDT, antimicrobial photodynamic therapy; BP-L, bisphosphonates-local; CAL, clinical attachment level; CHX, chlorhexidine; Mac/Linc-S, macrolides and lincosamides-systemic; NSAIDS-S, non-steroidal anti-inflammatory drugs-systemic; PD, probing depth; Pen+CA-S, penicillins+clavulanic acid-systemic; Pen+Nitro-S, penicillins+nitroimidazole-systemic; PVP-I, povidone iodine; Quino, quinolones; SRP, scaling and root planing; Tetra-S, tetracyclines-systemic; Tetra-L, tetracyclines-local.

Fig. 4

(A) Network plot and (B) cumulative rankograms (sensitivity analysis) for short-term clinical attachment level (CAL) gain after exclusion of six studies (Akincibay et al., 2008; Lu et al., 2012; Palmer et al., 1996; Coelho et al., 2023; Anwar et al., 2024; and Unsal et al., 1995) due to concerns regarding data reliability. Abbreviations: aPDT, antimicrobial photodynamic therapy; BP-L, bisphosphonates-local; CAL, clinical attachment level; CHX, chlorhexidine; Mac/Linc-S, macrolides and lincosamides-systemic; NSAIDS-S, non-steroidal anti-inflammatory drugs-systemic; Pen+Nitro-S, penicillins+nitroimidazole-systemic; PVP-I, povidone iodine; Quino, quinolones; SRP, scaling and root planing; Tetra-S, tetracyclines-systemic.