Rats (retired female breeder) EIP by ligatures Maxillary right M2
Nonsurgical treatment (therapeutic) Simvastatin prodrug 0.5 mg, 1.0 mg, and 1.5 mg Local injections of the drug/SIM/SIM-mPEG carrier 10 μL into the palatal gingiva between maxillary M1 and M2 Three weekly injections until euthanasia
↗ amount of uninflamed connective tissue in the M1-M2 interproximal area ↘ bone loss, especially with 1.5 mg SIM/SIM-mPEG ↘ percentage of neutrophils
Simvastatin limited periodontal breakdown by reducing bone loss and the extent of gingival inflammation
Rats (male) ACP (maxillary bone defect) Maxillary M1 extraction followed by socket healing, preparation of a critical-sized periodontal defect (2.0 mm diameter and 1.0 mm depth) on the mesial aspect of the M2, and manual removal of the residual bone and cementum on mesial aspect of M2
↗ neo-osteogenesis ↗ bone mineral density ↗ bone volume fraction ↗ number and thickness of trabeculae ↘ trabecular separation ↗ cementogenesis of the periodontal apparatus ↘ inflammatory cell infiltration
Simvastatin promoted osteogenic differentiation, reduced inflammation, and facilitated osteogenesis. Sequential PDGF-simvastatin delivery was able to accelerate osteogenesis, bone maturation, fiber realignment, and cementogenesis of the periodontal apparatus, thus accelerating periodontal regeneration
Rats (male) ACP (tooth-associated alveolar bone defect model) extraction of M1 followed by 4 weeks of socket healing, preparation of a critical-sized intrabony periodontal defect in the M1 edentulous ridge next to the mesial aspect of the M2 finished by a 2.6 mm diameter and 1.0 mm deep osteotomy (completely removing the mesial wall of the osteotomy), and cementum removal (to expose the mesial aspect of M2)
Surgical treatment (therapeutic) Simvastatin 1 mg PDLLA-PLGA hybrid microspheres encapsulating simvastatin/PDGF/BSA to fill the defects
↗ neo-osteogenesis (histologically) PDL fibers not inserted on the root surface (mainly parallel) ↗ bone volume fraction % (not significant)
Simvastatin histologically improved bone healing but better healing response was observed in the group receiving PDGF
Rats (female) ACP (fenestration defects) Defects 2 mm high, 4 mm wide, and 1.5 mm deep over mandibular molar roots
Nonsurgical treatment (therapeutic) Simvastatin 0.5 mg Local injection of 0.5 mg SIM per site dissolved in 70% ethanol or as SIM-ALN-CD Three weekly injections Treatment started 15 days after the defect preparation
↗ insignificant improvement of bone fill compared to other groups New cementum formation (not significant) But better bone healing response after systemic ALN administration followed by simvastatin injections
Simvastatin had a local bone healing effect which can be augmented by addition of certain other regenerative molecules like ALN
Dogs (male) ACP (maxillary bone defect) Extraction of all maxillary PM2 followed by healing and preparation of one-walled intrabony defects (: buccolingual, mesiodistal, and depth, respectively) on the mesial and distal sides of maxillary bilateral PM1 Removal of residual cementum by SRP
Surgical treatment (therapeutic) Lovastatin 0.1, 0.5, 1, or 2 mg per trilayer functional CS with the EGCG membrane area (cm2)
↗ new bone formation in the EGCG14-CS-lovastatin 1 group ® group group (42.32%) Evidence of new cementum deposition observed on the root surface No inflammatory cell infiltrate was noted in the EGCG14-CS-lovastatin 1 group Fibrous connective tissue approximated to the surgical defect
The trilayer functional CS membrane with EGCG and lovastatin enhanced periodontal regeneration and bone formation rate
Dogs (male) ACP (maxillary bone defect) Extraction of maxillary 2nd and 3rd incisors followed by 8 weeks of socket healing and, later, preparation of three-walled intrabony defects (: buccolingual, mesiodistal, and depth, respectively) on the mesial side of maxillary bilateral canines Removal of residual cementum by SRP
Nonsurgical treatment (therapeutic) Lovastatin 4 mg dissolved in chloroform to form a 3 wt % PLGA solution Local injections of PLGA-lovastatin-CS-tetracycline 0.3% nanoparticles prepared as a hydrogel by mixing with gelatin (10 mg/100 mm3) to fill the defects
↗ new deposits of cementum on the root surface ↗ active plasmacytoid osteoblastic rimming along the trabecular surface of the bone adjacent to the defect ↗ percentage of new bone formation (41.32%) No evident inflammation
PLGA-lovastatin-chitosan-tetracycline nanoparticles showed a good osteogenic potential. They promoted new bone and cementum formation
Rats (male) ACP (mandibular bone defect) Preparation of surgical defects 0.8 mm in diameter through the alveolar bone over the mesiobuccal root of the mandibular M1 bilaterally
Surgical treatment (therapeutic) Simvastatin 2.5% gel Defect was filled with 2.5% simvastatin gel Single topical application
↘ marrow spaces in simvastatin-treated defects ↗ collagen fibril organization ↗ OPN in bone matrix ↗ alveolar bone regeneration
Simvastatin gel improved the quality of the new bone and decreased bone resorption
Dogs (males and females) ACP (mandibular bone defect) Preparation of bilateral 3-walled intrabony defects () distal of the mandibular PM2 and mesial of the PM4 and class II furcation defects at the buccal furcation of the mandibular M1 measuring 4 mm occlusal apically and 4 mm buccolingually followed by healing and SRP of defect sites
Nonsurgical treatment (therapeutic) Simvastatin 0.5 mg or 2.0 mg in 30 μL methylcellulose gel Three weekly injections
↗ edentulous ridge thickness (29% greater with simvastatin) ↗ bone loss in class II furcation defects ↗ length of new cementum in the interproximal intrabony defect ↗ bone height with simvastatin (2 mg) No new cementum was observed in furcations
Simvastatin was not appropriate for the treatment of class II furcation defects. However, it improved bone healing in intrabony defects and edentulous ridges significantly
Rats (male) EIP by ligatures Maxillary M2 bilaterally
Nonsurgical treatment (therapeutic) Atorvastatin 2% containing CS gel Local 100 μL volume application every other day until euthanasia
↘ IL-1β, IL-6, and IL-8 ↗ IL-10 (time dependent) ↘ alveolar bone resorption (significantly with application and insignificantly with ATV alone) ↘ attachment loss Improvement of inflammatory and osteoclastic activity score over time
Atorvastatin with chitosan downregulated inflammation-mediated bone resorption
Rats (female) EIP by injection of E. coli LPS 10 μL of endotoxin injection (1 mg/mL of LPS in PBS) between M1 and M2
Nonsurgical treatment (preventative) Simvastatin 0.5 mg of simvastatin and 3.75 mg of SIM-ALN-CD in H2O Three weekly 12 μL injection bilaterally into the palatal/interproximal gingiva of M1 and M2 Treatment started one week before induction
↗ bone preservation during experimental periodontitis by prophylactic SIM-ALN-CD injection ↘ subsulcular inflammation ↘ alveolar bone loss ↘ OC number
Simvastatin protected against alveolar bone loss and soft tissue inflammation
Dogs (female) ACP (mandibular bone defect) Preparation of dehiscence defects () bilaterally on the lateral aspect of the mandibular PM2 mesial roots and removal of root cementum Split-mouth design
Surgical treatment (therapeutic) Simvastatin Graft surgery with HA grafts bilaterally covered with resorbable bilayer collagen membranes hydrated with 10 mg simvastatin (graft surgery performed at the time of defect preparation) Local injection 10 mg SIM (0.5 mg/kg) in ethanol (100 μL) Three weekly injections (one week after the graft surgery and defect preparation)
↗ width of new bone in edentulous ridge Distance between CEJ and the alveolar crest was more coronal in dehiscence defects treated with simvastatin (insignificant) Three weeks post-op after simvastatin injection (firm swelling about to in size), disappeared in 2 months
Simvastatin improved new bone formation where periosteum existed and did not induce severe side effects except for moderate swelling that, eventually, subsided
Nonsurgical treatment (therapeutic) Simvastatin 1 mg/mL ( gel solution) into the periodontal pocket SRP and irrigation with simvastatin Single injection
Nonsurgical treatment (therapeutic) Simvastatin 0.2 mg in 50 μL PBS topically injected into the buccal gingivae Twice a week for 70 days
↗ ALP activity ↗ bone nodule formation No inflammatory cells around the new bone ↘ bone loss Simvastatin recovered the ligature-induced alveolar bone resorption (46% reversal of bone height)
Simvastatin increased bone regeneration and reduced inflammation
Nonsurgical treatment (preventative) Simvastatin 0.5 mg/kg body weight orally Followed by laser therapy Treatment started 1 day before induction and daily until euthanasia
Rats (female ovarectomized) EIP by ligatures Mandibular right M1
Nonsurgical treatment (protective) Simvastatin 10-6 M, , 10-7 M subperiosteal injections (0.05 mL) Twice a week since the first day of ligature insertion to the 25th day
↘ periodontal breakdown ↘ bone loss in alveolar bone crest zone in a dose-dependent manner ()
Simvastatin reduced bone loss in a dose-dependent manner
Rat (female) EIP (ligature) Maxillary M2 bilaterally
Nonsurgical treatment (therapeutic) Simvastatin SIM-PPi conjugate Different treatments including SIM-PPi (dissolved in 25%, 2.56 mg, equivalent to 1.5 mg SIM) and SIM acid (dissolved in PBS, 1.56 mg, equivalent to 1.5 mg of SIM) locally injected (10 μL) into the palatal gingiva between the maxillary M1 and M2 On the first day of weeks 1, 2 and 3 after ligature placement
↗ alveolar bone crest preservation with SIM-PPi ↗ bone volume ↗ trabecular thickness ↗ trabecular number ↘ trabecular separation ↘ neutrophil and lymphocyte score ↘ OC score
Simvastatin improved periodontal bone regeneration and decreased periodontal inflammation
