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Table 1 Summary of the studies on animal models

From: The impact of simvastatin intervention on the healing of bone, soft tissue, and TMJ cartilage in dentistry: a systematic review and meta-analysis

Author, study type

Procedure and animal type

Group and study type

Key results

Sherif et al. 2016

RCT

20 rats, bilateral extractions

Test group: 2.5% SIM gel

Control: no treatment

Rats sacrificed at 1st, 2nd, 3rd, and 4th week

Buccolingual ridge width measured with bone calipers

Single topical application of 2.5% simvastatin gel improves the quality of the new bone of the healing extraction socket and decreases bone resorption

Wu et al. 2008

RCT

60 rats, extraction

Test group (30): SIM 1 mg/1 ml PLGA scaffold

Control: PLGA

Rats sacrificed at 1, 2, 4, 8, and 12 weeks.

Histology and BMD examination

Higher bone formation rate and quality were found during the extraction socket healing in the experimental group than in the control group at all time points except for 1 week

Vaziri et al. 2007

RCT

49 rats, bilateral ovariectomy

7 groups with ligature placed in all except 1 (sham)

Group 1 (N = 7), ovariectomy (OVX) plus simvastatin (10–6 M); group 2 (N = 7), OVX plus simvastatin (3·10–7 M); group 3 (N = 7), OVX plus simvastatin (10–7 M); group 4 (N = 7), OVX plus normal saline; group 5 (N = 7), OVX group; group 6 (N = 7), ligature without OVX; group 7 (N = 7), sham surgery without OVX and ligature.

Sacrificed after 4 weeks.

Radiologic and histologic analysis. Bone loss, attachment loss

Simvastatin inhibits periodontal attachment loss with the least in 10–6 M group. 3·10–7 M had the least effect on the inhibition.

Local application of simvastatin shows protective features against the impact of periodontitis on attachment apparatus and alveolar bone

Killeen et al. 2012

RCT

Split-mouth study

65 rats, fenestration defects

Test group: 0.5 mg simvastatin in ethanol (SIM-EtOH); 2) 0.5 mg simvastatin in alendronate–cyclodextrin conjugate (SIM-ALN-CD); control group: 3) EtOH alone; 4) ALN-CD alone; or 5) no injections.

Sacrificed at 21 days, 48 days.

Histometric analysis

Twofold to threefold more new bone width (0.004) was seen in the fenestration defect treatment with the use of systemic ALN after SIM-EtOH injections as compared to local SIM/ALN-CD preparations or short-term SIM-EtOH injections

Kiliç E

et al. 2008

RCT

18 rabbits, unilateral distraction osteogenesis

Experimental group I: 2.5 mg/ml of SIM/0.2 g of gelatin sponge applied locally

Experimental group II: 10 mg SIM systemically

Control: no treatment

Sacrificed at 14 days

Peripheral quantitative computed tomography, and with histomorphometry

No SSD in the amount of regenerate bone during distraction osteogenesis between the systemic simvastatin group and control group or between the local simvastatin group and control group

Rutledge et al. 2011

Split-mouth study

4 beagle dogs, dehiscence defects bilaterally

Local placement of porous HA-collagen grafts with resorbable membranes with or without 10 mg SIM followed by local injections.

Sacrificed after 2 months

Histomorphometry

Locally injected SIM can induce modest amounts of new bone formation within the dehiscence defects in closed injection sites over a periosteal surface

Ozec et al. 2007

RCT

23 rats, critical-sized defects in the mandibles

Experimental group: 2.5 mg/Ml SIM mixed with 0.02 g of gelatin sponge.

Passive control

Active control: gelatin sponge mixed with water

Sacrificed at day 14

Radiology and histology assessment

New bone formation and density of new bone in mandibular defects are more significant in the experimental group than control groups

Anbinder et al. 2007

RCT/Split mouth

54 rats, two groups: ovariectomized (OVX) or sham operated

Experimental group: simvastatin (SIN–25 mg/kg), Active control: sodium alendronate (ALN–2 mg/kg) or Passive control: water (control) orally.

Sacrificed after 35 days

Radiographic bone density measured

No SSD in alveolar bone formation between ALN and SIM group

George MD et al. 2013

RCT

32 rats, randomized

5 groups. TMJ inflammation induced

I: Controls

II: ETH III: 0.1 mg SIM, 3) IV: 0.5 mg SIM, V: 0.15 mg TH.

Time: 28 days

H&E

SIM & TH reduced the TMJ articular layer thickness, 0.5 mg decreased inflammation

Holwegner et al. 2015

RCT

44 mature rats

CFA induced inflammation in right TMJ

6 groups

I: CFA + 0.5 SIM

II: CFA + EtOH

III: CFA + 0.15 TH

IV: CFA + SIM + H V: CFA

VI: Control (left)

Time: 4 weeks

CT, BV, BMD

CFA combination groups: TMJ ramus height > than CFA alone

BV:CFA + 0.5 SIM > CFA + SIM + TH

Condylar width, bone density: least in steroid grp as compared to SIM

  1. SIM simvastatin, HA hydroxyapatite, TH triamcinolone hexacetonide, CFA complete Freund’s adjuvant, EtOH ethanol