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Table 1 The effect of Statins on dental and oral diseases based on systematic review and meta-analysis

From: The effects of statins on dental and oral health: a review of preclinical and clinical studies

Author, year

Type of the study

Number of included studies

Intervention/control

Local or systemic delivery of statins

Main outcomes

Bertl K et al. 2017 [32]

Systematic review and meta-analysis of periclinical in vivo trials

16 Studies in experimentally induced periodontitis (EIP) models and 7 studies in acute/chronified periodontal defect (ACP) models

Effect of local and/or systemic statin use on periodontal tissues in preclinical in vivo studies

Local and systemic use

Statin use (Simvastatin, Atorvastatin or Rosuvastatin) in periodontal indications has a positive effect on periodontal tissue parameters.

Meta-analysis based on 14 EIP trials confirmed a significant benefit of local and systemic Statin use in terms of alveolar bone level/amount; meta-regression revealed that Statin type exhibited a significant effect in favor of Atorvastatin

Akram Z et al. 2017 [43]

Meta-analysis of clinical trials

11

Treatment with statins as an adjunct to scaling and root planing (SRP) in the treatment of chronic perio-dontitis (CP) compared to SRP with placebo gel

Local and systemic use

All of the studies showed that SRP and adjunctive Statin delivery was effective in the treatment of CP at follow up. In all of the included studies, periodontal inflammatory parameters (PD, CAL, and BD fill) showed significantly higher improvements in the test group (Statin delivery + SRP) compared to the control group (SRP + placebo/SRP)

Bertl K et al. 2017 [44]

Systematic review and meta-analysis of clinical trials

19

Treatment with statins as an adjunct to non-surgical and surgical periodontal therapy compared to no treatment or periodontal therapy alone

Local and systemic use

Significant additional clinical and radiographic improvements are obtained after local, but not systemic, statin use as an adjunct to SRP in deep pockets associated with intrabony defects and seemingly with furcation defects; intrasurgical statin application seems similarly beneficial.

There are differences among the various statin types, in terms of efficacy, and RSV appears as the most efficacious for local application

Kellesarian SV et al. 2017 [47]

Systematic review of prospective animal trials

19

Local and systemic statin delivery to enhance the osseointegration of implants.

Local and systemic use

On experimental grounds, local and systemic statin delivery seems to enhance osseointegration

Ting M et al.2016 [51]

Systematic review of in vitro trials

26

Orally adminis- tered statins as an antimicrobial agents for microorganisms infecting oral and perioral tissues

Systemic use

Studies show that most statins exhibit antimicrobial effects against various oral microorganisms. Simvastatin is most effective against the periodontal pathogens Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, and against most dental plaque bacteria, including Streptococcus mutans. Statins also exhibit antiviral properties against human cytomegalovirus, hepatitis B virus, and hepatitis C virus, and have antifungal properties against Candida albicans, Aspergillus fumigatus, and Zygomycetes spp.

Pavan LM et al.2015 [124]

Systematic review of in vitro or in vivo animal trials

18

Treatment with statins alone or as an adjunct to chemotherapy and/or radiotherapy approaches in the treatment of head and neck squamous cell carcinom (HNSCC) compared to no treatment or chemotherapy and/or radiotherapy approaches alone.

Systemic use

Statins have a significant effect on HNSCC cell lines with respect to cell viability, cell cycle, cell death, and the regulation of protein expression levels involved in pathways of carcinogenesis, which corroborates with the potential in vitro anti-tumor effects

De Monès et E al. 2014 [71]

A narrative review of preclinical and clinical studies

21

Treatment with statins as an agent to reduce alveolar bone resorption following extraction or periodontal disease

Local and systemic use

Statins reduced significantly alveolar bone resorption observed during periodontal disease and after tooth extraction. Oral administration was effective using high statin concentrations although local administration using a biodegradable carrier was effective with lower concentrations

Estanislau IM et al. 2015 [48]

Systematic review of clinical trials

11

Treatment with statins as an adjunct to scaling and root planing (SRP) in the treatment of chronic perio- dontitis compared to SRP with placebo.

Local and systemic use

Statins have beneficial effects, stimulating bone formation, decrease of inflammation and immunomodulation. This implies that this group of drugs might have a great potential to improve the therapeutic effect in the treatment of periodontitis, since they are safe and not costly, but not to substitute the standard of periodontal treatment, which consists in removing microorganisms

Fu JH et al. (2012) [91]

Review

7 Relevant papers, which were not reviews or in vitro studies. All animal model

Fluvastatin, Simvastatin and Rosuvastatin

Local and systemic

Evidence seems to suggest that statins may increase bone formation, which may be beneficial to dental implant healing

Moraschini V et al. 2018 [92]

Systematic review of animal studies

12

Topical and systemic statins as a pro-osteogenic agent to enhance the osseointegration of dental implants

Topical and systemic use

Findings of all of the selected studies indicated that statins (simvastatin and fluvastatin) had a statistically significant positive effect on bone formation around implants

Meza-Mauricio J et al. 2018 [49]

Systematic review and meta-analysis of clinical trials

13

Treatment with statins as adjuncts to scaling and root planing (SRP) in chronic periodontitis in comparison to the SRP alone or with placebo

Local

SRP + statin treatment (with at least 6 months of follow-up after randomization) had statistical significant effects on clinical attachment level gain, probing pocket depth reduction, modified sulcus bleeding index, and intrabony defect depth compared with SRP alone or with placebo

Muniz Fwmget al. 2018 [50]

Systematic review and meta-analysis of clinical trials

10

Treatment with statins as adjunct to mechanical periodontal therapy compared with mechanical periodontal therapy and a placebo gel

Local

Taking of simvastatin rosuvastatin, and atorvastatin as adjunct to mechanical periodontal therapy resulted in a dramatic reduction in probing pocket depth compared with mechanical periodontal therapy and a placebo gel.

A significant improvement was found in resolution of intrabony defect in repose to the simvastatin and rosuvastatin use as an adjunct therapy compared with control group.

Taking simvastatin as an adjunct therapy was significantly associated with clinical attachment level gain compared with control group.

In all of the measured parameters, simvastatin is the only drug with additional beneficial effects