The use of Subgingivally Delivered Simvastatin in the Treatment of Chronic Periodontitis

Author: caterina frascolino
Date: 05/01/2014


Infections that involve teeth structure are known as periodontal disease. Still today there isn’t a precise classification of this disease, however they are divided in two categories: gingivitis and periodontisis.


Periodontitis is a set of inflammatory diseases affecting the periodontium , which are the tissues that surround and support the teeth. Periodontitis involves the progressive loss of the alveolar bone around the teeth. If it’s not treated it can lead to the loosening and subsequent loss of teeth. Periodontitis is caused by microorganisms that adhere to and grow on the tooth's surfaces, along with an overly aggressive immune response against these microorganisms. A diagnosis of periodontitis is established by inspecting the soft gum tissues around the teeth with a probe (a clinical examination) and by evaluating the patient's X-ray films (a radiographic examination), to determine the amount of bone loss around the teeth. Specialists in the treatment of periodontitis are periodontists; their field is known as "periodontology" or "periodontics".

Many treatment modalities are available to achieve the goal of periodontal therapy. This includes non surgical periodontal therapy, such as scaling and root planing alone or SRP plus systemic or local antimicrobial/anti-inflammatory agents, and surgical periodontal therapy. Autologous bone is the current gold-standard graft material for the treatment of skeletal defects and fracture repair. However, the need for a second surgical site and the limited supply of bone available have led to the development of various alternative materials, such as pharmacologial compompounds. If pharmacologic compounds can upregulate the necessary autogenous growth factors to stimulate bone growth, this approach may prove to be a cost-effective way to correct bone defects.

Chronic inflammatory periodontal disease

Like mentioned above, periodontitis are disease that hit the periodontium. Based on clinical parameter, such as scaling, divide them in chronic and aggressive. Studies using simvastatin, combined with other treatments in the sub-gingival region were conducted on the chronic periodontal disease. The chronic inflammatory periodontal disease is highly prevalent, especially in late middle age, when cardiovascular disease is also common. It has been defines as “an infectious disease resulting in the inflammation with in supporting tissues of the teeth, progressive attachment loss and bone loss”. In periodontitis, the production of pro-inflammatory cytokines and tissue-degradative enzymes is initiated and advanced by oral bacterial infection, ultimately resulting in the destruction of periodontal tissue. Since it’s an inflammatory disease occurring adjacent to bone, it leads to bone reabsorption, creating bony defects that may cause tooth loss. Like written above, there are various affective methods effective that repair these defects, creating space, and stimulating host bone formation through the use of a graft, guided tissue-regeneration, and growth factors.


The question now is, what is Simvastatin?
Simvastatin is a synthetic compound. It derives from the product of the fermentation of Aspergillus terreus, which belongs to the Statin family. Statins such as SMV, are specific competitive inhibitors of 3-hydroxy-2-methyl-glutaryl coenzyme A (HMG- CoA) reductase. These agents are widely used to lower cholesterol, and they provide an important and effective approach for the treatment of hyperlipidemia and arteriosclerosis. Statins also seem to modulate bone formation by increasing the expression of bone morphogenetic protein, inflammation, and angiogenesis, thus providing a new direction in the field of periodontal therapy. Various studies showed that SMV assists in bone regeneration as well as the anti-inflammatory effect when delivered or applied locally (Statins: A new era in local drug delivery, 2012).
The effectiveness of Simvastatin was demonstrated in numerous clinical trials, such as one done in 2010 by Pradeep AR, Thorat MS, that we analized (Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: a randomized clinical trial, 2010).

Clinical Trial:

During the clinical trial, which also uses Simvastatin to treat Chronic periodontitis, 64 patients, aged 25 to 45 years (33 males and 31 females) were enrolled in this study. After subject selection, 30 patients were randomly assigned to two treatment groups: group one was treated only with scaling and root planning (SRP); group two was treated with SRP plus simvastatin (1.2 mg/0.1 ml).
For standardization, 0.1 ml prepared SMV gel (1.2 mg/0.1 ml) was injected into the periodontal pockets using a syringe. No periodontal dressing was applied after delivery of the drug because it would have caused swelling and occlusion of the periodontal pocket. After placing the gel in situ, patients were instructed to refrain from chewing hard or sticky foods, brushing near the treated areas, or using any inter-dental aids for one week. Adverse effects were noted at recall visits, and any supra-gingival deposits were removed.


60 of 64 patients completed the study. Four patients were excluded for reasons unrelated to the study. Sixty treatment sites were evaluated for clinical parameters at baseline (before scaling and root planning) and at 1, 2, 4, and 6 months. No opposing reaction was observed in any subject from the test group, and no patient reported any discomfort. Healing was uneventful. All subjects tolerated the drug, without any post-application complications.

Parameters that didn’t have any significant difference in the two groups were:
1) Evaluation of Oral Hygiene: both groups maintained comparable levels of oral hygiene throughout the study.
2) PD: probing depth
3) CAL: clinical attachment loss
4) Analysis of SMV Concentration in GCF: SMV in GCF peaked at 2 hours after application (11.43 – 0027 mg/ml). The mean concentrations on days 7, 14, 21, and 30 indicate that SMV was retained in this target compartment for a long period, suggesting a controlled release of the drug until day 30.

Parameters that had a significant difference within the two groups:
1) mSBI (modified sulcus bleeding index): A statistically significant decrease in mSBI scores from baseline was found in both groups. However, the decrease was greater in group 2 (2.32 – 0.80) compared to group 1 (0.50 – 0.68) at 6 months.
2) IBD (Radiographic Evaluation of Intrabony Defects) Fill: There was a greater decrease in mean IBD in group 2 (1.41 – 0.74 mm or 32.54%) compared to group 1 (0.09 – 0.58 mm or 2.16%), and it was statistically significant.


There was a greater decrease in gingival index and PD and more CAL gain with significant IBD fill with locally delivered SMV in patients with chronic periodontitis. These observations may give new direction in the field of periodontal regeneration, to achieve the goal of regeneration without any invasive procedures, thereby causing less discomfort to the patients. Other clinical trials were done on patients who were smokers and the results confirmed better results when Simvastatin was used compared to placebo (Simvastatin local drug delivery in smokers with chronic periodontitis: a randomized controlled clinical trial, 2013).
However, long term studies, using different vehicles and concentrations of SMV, should be carried out to affirm the observations of the study.
Simvastatin is a widely used pharmaceutical. It may also be used to decrease the amount of cholesterol and other fatty substances children’s’ blood with familial heterozygous hypercholesterolemia or it can be used to decrease the risk of heart attacks, strokes and to decrease the need for surgery to improve blood flow in people who have medical conditions that put them at high risk of developing heart and blood vessel problems.
However it is a pharmaceutical with numerous side effects. It can cause constipation, stomach pain, nausea, headache, memory loss or forgetfulness, confusion. These side effects can develop and become serious. Although it brings a lot of positive effects in medicine, it also brings along many negative ones. This is why Simvastatin is still studied today, in order to determine whether the positive effects overcome the negative ones (Paradoxical Negative HDL Cholesterol Response to Atorvastatin and Simvastatin Treatment in Chinese Type 2 Diabetic Patients,2013).

Bellagarda Giorgia, Frascolino Caterina

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