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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, yearType of the studyNumber of included studiesIntervention/controlLocal or systemic delivery of statinsMain outcomes
Bertl K et al. 2017 [32]Systematic review and meta-analysis of periclinical in vivo trials16 Studies in experimentally induced periodontitis (EIP) models and 7 studies in acute/chronified periodontal defect (ACP) modelsEffect of local and/or systemic statin use on periodontal tissues in preclinical in vivo studiesLocal and systemic useStatin 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 trials11Treatment with statins as an adjunct to scaling and root planing (SRP) in the treatment of chronic perio-dontitis (CP) compared to SRP with placebo gelLocal and systemic useAll 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 trials19Treatment with statins as an adjunct to non-surgical and surgical periodontal therapy compared to no treatment or periodontal therapy aloneLocal and systemic useSignificant 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 trials19Local and systemic statin delivery to enhance the osseointegration of implants.Local and systemic useOn experimental grounds, local and systemic statin delivery seems to enhance osseointegration
Ting M et al.2016 [51]Systematic review of in vitro trials26Orally adminis- tered statins as an antimicrobial agents for microorganisms infecting oral and perioral tissuesSystemic useStudies 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 trials18Treatment 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 useStatins 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 studies21Treatment with statins as an agent to reduce alveolar bone resorption following extraction or periodontal diseaseLocal and systemic useStatins 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 trials11Treatment 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 useStatins 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]Review7 Relevant papers, which were not reviews or in vitro studies. All animal modelFluvastatin, Simvastatin and RosuvastatinLocal and systemicEvidence 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 studies12Topical and systemic statins as a pro-osteogenic agent to enhance the osseointegration of dental implantsTopical and systemic useFindings 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 trials13Treatment with statins as adjuncts to scaling and root planing (SRP) in chronic periodontitis in comparison to the SRP alone or with placeboLocalSRP + 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 trials10Treatment with statins as adjunct to mechanical periodontal therapy compared with mechanical periodontal therapy and a placebo gelLocalTaking 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