The aim of this review was to update the evidence of new approaches to non-surgical therapy (NSPT) in the treatment of periodontitis. Preclinical and clinical studies addressing the benefits of adjunctive antimicrobial photodynamic therapy, probiotics, prebiotics/synbiotics, statins, pro-resolving mediators, omega-6 and -3, ozone, and epigenetic therapy were scrutinized and discussed. Currently, the outcomes of these nine new approaches, when compared with subgingival debridement alone, did not demonstrate a significant added clinical benefit. However, some of these new alternative interventions may have the potential to improve the outcomes of NSPT alone. Future evidence based on randomized controlled clinical trials would help clinicians and patients in the selection of different adjunctive therapies.

Background: Enamel matrix derivative (EMD) has recently been shown to promote periodontal regeneration in vivo. Insulin‐like growth factor‐I (IGF‐I) is a potent modulator of periodontal regeneration stimulating cell proliferation, differentiation, synthesis of type I collagen, and non‐collagenous proteins. However, the biochemical effects of these factors on periodontal ligament (PDL) fibroblasts are not completely understood. The objective of the present study was to evaluate the effect of EMD, IGF‐I, and the combination of these two factors on the proliferation, adhesion, migration, and expression of type I collagen in PDL fibroblasts.Methods: The proliferation rate was measured by automated cell counting and immunohistochemical expression of proliferating cell nuclear antigen (PCNA). The cell adhesion was analyzed by a colorimetric assay and cell migration was measured in Boyden chambers. Type I collagen expression and production was determined by semi‐quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA), respectively.Results: The results indicated that the proliferation of PDL fibroblasts was significantly stimulated by EMD and EMD plus IGF‐I in a dose‐ and time‐dependent manner. EMD, IGF‐I, and the combination of both factors had no effects on cellular migration and adhesion or expression and production of type I collagen.Conclusion: Our results showed that EMD, IGF‐I, and the combination of both factors stimulated PDL fibroblast proliferation, whereas these factors did not affect adhesion, migration, or expression of type I collagen of these cells. J Periodontol 2004;75:498‐504.

Adjunctive therapeutic strategies that modulate the inflammatory mediators can play a significant role in periodontal therapy. In this double-blind, placebo-controlled study, 60 subjects diagnosed as periodontitis patients were evaluated for 28 days after periodontal treatment combined with selective cyclooxygenase-2 (COX-2) inhibitor. The experimental group received scaling and root planning (SRP) combined with the Loxoprofen antiinflammatory drug (SRP+Loxoprofen). The control group received SRP combined with placebo (SRP+placebo). Plaque index (PI), probing pocket depth (PD) and bleeding on probing (BOP) were monitored with an electronic probe at baseline and after 14 and 28 days. Both groups displayed clinical improvement in PD, PI and BOP. They also showed statistically similar values (p>0.05) of PD reduction on day 14 (0.4 mm) and on day 28 (0.6 mm). At the baseline, few deeper sites (>7 mm) from SRP+Loxoprofen group were responsible and most PD reduction was observed after 14 days (p7 mm) after 14 days in the SRP+Loxoprofen group was significantly lower (p

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14⁺) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14⁺ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14⁺ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.