Contribution of Statins towards Periodontal Treatment: A Review

Abstract

The pleiotropic effects of statins have been evaluated to assess their potential benefit in the treatment of various inflammatory and immune-mediated diseases including periodontitis. Herein, the adjunctive use of statins in periodontal therapy in vitro, in vivo, and in clinical trials was reviewed. Statins act through several pathways to modulate inflammation, immune response, bone metabolism, and bacterial clearance. They control periodontal inflammation through inhibition of proinflammatory cytokines and promotion of anti-inflammatory and/or proresolution molecule release, mainly, through the ERK, MAPK, PI3-Akt, and NF-κB pathways. Moreover, they are able to modulate the host response activated by bacterial challenge, to prevent inflammation-mediated bone resorption and to promote bone formation. Furthermore, they reduce bacterial growth, disrupt bacterial membrane stability, and increase bacterial clearance, thus averting the exacerbation of infection. Local statin delivery as adjunct to both nonsurgical and surgical periodontal therapies results in better periodontal treatment outcomes compared to systemic delivery. Moreover, combination of statin therapy with other regenerative agents improves periodontal healing response. Therefore, statins could be proposed as a potential adjuvant to periodontal therapy. However, optimization of the combination of their dose, type, and carrier could be instrumental in achieving the best treatment response.

Figure 1

Effect of statins on the inflammatory-immune crosstalk. Direct LFA1 site binding by lipophilic statins decreases ICAM-1 presentation leading to reduced leukocyte chemotaxis and antigen presentation. Statins inhibit MHC-II induction by IFN-γ leading to decreased T-cell activation. Statins lower mevalonate release, leading to resolution of inflammation via the ERK, MAPK, and PI3K-Akt pathways.

Figure 2

Effects of statins on several pathways involved in bone metabolism. Statins decrease osteoclastogenesis via RANK/RANKL and NF-κB signaling. Statins promote osteogenesis by increasing VEGF, BMP2, and TGF-β expression through the PI3-Akt pathway. Statins prevent inflammation-mediated bone resorption by decreasing TNF-α, via TNFR.

Figure 3

Antibacterial effect of statins. Statins arrest bacterial growth and disrupt their membrane stability by decreasing cholesterol. Statins increase bacterial clearance by decreasing NF-κB and ROS signaling (via the PI3K-Akt and NADPH oxidase pathways, respectively) and by enhancing proresolution molecule release.

Figure 4

Selection of the studies.

Figure 5

Pleiotropic effects of statins in the context of periodontitis management. Statin biological properties might be of interest for the management of periodontitis as they act on each tissular compartment and mechanisms including inflammatory-immune crosstalk, bone metabolism and bacterial clearance.