A network meta-analysis of randomized controlled trials evaluating the evidence of pharmacological agents and growth factors in the regeneration of bony defects in chronic periodontitis.

Abstract

<h4>Background</h4>Periodontitis is a chronic, multifactorial infectious disease affecting the oral cavity, destroying the periodontal supporting tissues, including alveolar bone resorption and loss of clinical attachment. These changes can result in the formation of intrabony defects and if left untreated, it can ultimately result in tooth loss. To enhance periodontal regeneration, several pharmacologic agents-alendronate (ALN), rosuvastatin (RSV), atorvastatin (ATV), metformin (MF), and melatonin (ML)-have demonstrated promising osteoanabolic and anti-inflammatory effects. When combined with platelet-rich fibrin (PRF), these agents may further enhance clinical and radiographic outcomes. This study aimed to assess the adjunctive benefits of various drug-PRF combinations on clinical attachment level (CAL) gain and bone fill (BF) in chronic periodontitis patients.<h4>Methods</h4>This network meta-analysis (NMA) adhered to PRISMA-NMA standards and was recorded in the PROSPERO registry (CRD42024600432). An extensive literature search was conducted using the PubMed/ Medline, Wiley Online Library, Embase, and CENTRAL databases identified randomized controlled trials (RCTs) published after 2016. The analysis included ten studies comprising RCTs with 393 participants containing intrabony or furcation region defects and follow-up periods of 6 and 9 months.<h4>Results</h4>PRF with MF demonstrated the highest efficacy for CAL gain (SUCRA 1.00), followed by PRF with ALN (0.60) and RSV (0.70). For bone fill, PRF with ALN ranked highest (SUCRA 0.90), followed by RSV (0.90) and MF (0.60). ML and ATV combinations showed modest effects, while PRF alone and placebo consistently ranked lowest (SUCRA ≤ 0.20).<h4>Conclusions</h4>PRF combined with MF, ALN, and RSV appears to be the most effective therapeutic option for managing bony defects in chronic periodontitis. Future studies should confirm these findings through additional large and long-term clinical trials.<h4>Clinical relevance</h4>The study provides clinically relevant evidence supporting the adjunctive use of pharmacologic agents with PRF to optimize regenerative outcomes. Such combinations can improve bone fill and attachment gain, offering predictable benefits for patients with chronic periodontitis.