**1. Introduction**

Atherosclerosis and ischemic heart disease are the most common causes of death in the world. Hyperlipidemia is one of the most important risk factors for the development of diseases of the cardiovascular system. Prevention and treatment are based on lowering the serum concentration of atherogenic lipoproteins and triglycerides. Statins are one of the most commonly used drugs for this purpose. As structural analogs, they inhibit cholesterol synthesis in liver cells by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-CoA (HMGCoA) reductase. People treated with statins generally continue with this therapy for the rest of their lives. Statins consumption is on the rise and in some countries, those drugs can be bought without a prescription [1].

Statins are rapidly absorbed and the maximum plasma concentration is within 4 hours [2]. The optimal time to take a statin is in the evening before bedtime when the synthesis of endogenous cholesterol is most intense [3]. They are metabolized largely by cytochrome P450 (CYP450). This metabolic pathway is particularly important for lipophilic statins that are highly susceptible to oxidative reactions at cytochrome P450 [4]. Elimination after metabolization in the liver is done mainly by bile. Therefore, hepatic dysfunction is a risk factor for statin-induced myopathy. Hydrophilic statins that bypass the metabolic pathway *via* cytochrome P450 are excreted largely unchanged by the liver and kidneys.

Statins are generally well tolerated and serious side effects are very rare. Mild and transient side effects that may occur include bloating, constipation, diarrhea, abdominal pain, general weakness, and dizziness [5].

Caution should be exercised with regard to dental procedures in patients receiving warfarin therapy because statins may increase the concentration of warfarin in plasma and dose adjustment of warfarin is sometimes required [6]. It is important to note that macrolides, although rarely prescribed in dental clinics, can increase plasma statin concentrations and consequently cause myopathy. It is recommended that statins are discontinued during macrolide therapy if treatment with another group of antibiotics is not possible [7].

Statins have an antibacterial effect against oral pathogens, especially against *Aggregatibacter actinomycetemcomitans* and *Porphyromonas gingivalis* [8]. They also have an antifungal effect against *Candida albicans*, *Aspergillus fumigatus*, and Zygomycetes. Statins modulate the immune response to inflammation and sepsis and reduce the CRP inflammatory parameter by reducing the level of inflammatory interleukin 6. They also increase the level of bone morphogenic protein-2 (BMP-2), stimulate osteoblast activity in bone matrix formation, and promote osseointegration of dental implants [9, 10]. There are several factors that may influence implant and osseointegration such as type of implant-abutment connection. Menini et al. do research on internal versus external connections. They measured peri-implant marginal bone level (MBL) changes, plaque index (PI), probing depth (PD), and bleeding on probing (BoP), evaluated at implant insertion and at 3, 6, and 12 months post-loading. After 12 months, both implant connections showed good clinical features, without inflammation or bone resorption [11]. Animal studies have shown that simvastatin promotes angiogenesis, osteoblast differentiation, and periodontal ligament cell development in both topical and systemic administrations. Angiogenesis and fibrinogenesis are prompted by stimulation of vascular endothelial growth factor (VEGF) in a not yet fully elucidated way [12, 13]. Studies in the United States have shown that more than one-third of the adult population over the age of 45 use systemic statin therapy, putting these drugs in a position to be used as essential therapeutics in dentistry, especially in oral surgery, dental implantology, and periodontology [14].

### **2. Materials and methods of search strategy**

#### **2.1 Literature search strategy**

The keywords used in the web search were: (1) statins + osseointegration; (2) statins + implants; (3) statins + implants + osseointegration; (4) BIC + statins; (5) BIC + statins + osseointegration; (6) simvastatin + osseointegration; (7) simvastatin + *Use of Statins in Dental Implantology and Their Impact on Osseointegration: Animal Studies DOI: http://dx.doi.org/10.5772/intechopen.108953*

implants; (8) rosuvastatin + osseointegration + implants; (9) fluvastatin + osseointegration; and (10) fluvastatin + implants (**Figure 1**).

Keywords were entered into PubMed, Cochrane Central, and Google Scholar databases. The search inclusion criteria were published studies from the creation of the databases to the end of April 2021. Articles that do not have English abstract with the following keywords were eliminated: statins + endodontics, statins + pulpitis, statins + direct pulp coverage, and statins + stem cells. This was done by reviewing the reference list of included articles to identify the potential of an acceptable study. *In vitro* studies investigating oral and perioral microorganisms found in the oral cavity were included in the review. Studies published in languages other than English language were included only if an abstract was available in English. Studies inclusion criteria in this systematic review were if they met the following eligibility

**Figure 1.** *Flowchart of article selection process in the review.*

criteria: original studies in English (clinical and animal trials); evaluation of titanium implants influenced by statins; the presence of a control group; and outcome data considering bone implant contact (BIC), mechanical tests, or other histological evaluation. Studies exclusion criteria was articles using implants inserted into the medullar cavity, Letters to the editor, reviews, case series, case reports, and *in vitro* studies were also exclusion criteria for this chapter.

### **2.2 Review and identification of acceptable studies**

In the initial phase, one author reviewed abstracts of all papers to identify the studies that could have the inclusion criteria. If the abstract met the inclusion criteria, then the full text of the paper was obtained, evaluated, and cited in the review paper. The second author checked all the listed works and the criteria for inclusion or exclusion of certain articles.
