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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
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
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
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
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
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
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
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
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
SIM & TH reduced the TMJ articular layer thickness, 0.5 mg decreased inflammation
Holwegner et al. 2015
44 mature rats
CFA induced inflammation in right TMJ
6 groups
I: CFA + 0.5 SIM
III: CFA + 0.15 TH
VI: Control (left)
Time: 4 weeks
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