Local Simvastatin Effects on Mandibular Bone Growth and Inflammation

Stein, David E.; Lee, Yeon-Ju; Schmid, Marian J.; Killpack, Byron; Genrich, Mikala A.; Narayana, Nagamani; Marx, David B.; Cullen, D. M.; Reinhardt, Richard

doi:10.1902/jop.2005.76.11.1861

Cited by 153 publications

(205 citation statements)

References 32 publications

(20 reference statements)

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“…The same occurred with the osteoclasts with greater scores in the simvastatin group compared with the control group. These results are in agreement with other studies [16][17][18][19]26 . In the late period of regeneration, simvastatin was able to stimulate a greater presence of osteoblasts and subsequent bone formation.…”

Section: Discussionsupporting

confidence: 94%

“…We applied the simvastatin in gel form through an association with a vehicle: hidroxipropilenometilcelulose (HPMC), which is biocompatible, stable and able to slowly release simvastatin in its action site. The choice of the concentration of simvastatin (1.0 mg / ml gel 0.5 HPMC) was based on other reports that used similar doses: 2.2 mg 17 , 0.5 mg 11,18 , 0.1 mg / 0.5 mg / 1.0 mg / 1.5 mg / 2.2 mg 19 . There are reports that the local use of highdose simvastatin impaired bone healing, which suggests that there might have been a stimulant effect on osteoclastic activity, which would result in the resorption of new bone formations 9 .…”

Section: Immunohistochemistry Evaluationmentioning

confidence: 99%

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The effect of simvastatin on the regeneration of surgical cavities in the femurs of rabbits

Rosselli

Martins

et al. 2014

Acta Cir. Bras.

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PURPOSE:To evaluate the effect of a local application of simvastatin gel in repairing bone defects in the femurs of rabbits. METHODS:Two standard surgical cavities were created in the femoral epiphysis of 18 rabbits. In the simvastatin group (SG), the cavities were filled with a collagen sponge soaked in 0.5 ml of a simvastatin (1 mg) gel, and the cavities were covered with a biological membrane. The bone cavities in the second group (control group) were filled with a blood clot and covered with a biological membrane.On the 7 th, 21st and 42 nd days, six animals in each group were euthanized, and the femurs were subject to histological evaluation (vascularity, fibrosis, reactive bone formation, osteoblasts, and osteoclasts) and immunohistochemical (anti-VEGF and anti-osteocalcin) analysis.The results were analyzed using a Wilcoxon test (p<0.05). RESULTS:There were significant differences between the two groups: the SG had greater scores in comparison with the CG in terms of the degree of vascularity on the 7t h and the 21st days, fibrosis on the 21 st day, bone formation reaction on the 21 st and the 42 nd days and the number of osteoblasts and osteoclasts on the 42 nd day. The immunohistochemical expression was also greater for osteocalcin and VEGF on the 7 th, 21st and 42 nd days. CONCLUSION:Surgical defects created in rabbit femurs were treated locally with simvastatin gel to stimulate bone repair, which promoted an ameliorative effect in the morphological and immunohistochemical markers of bone regeneration.

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Section: Discussionsupporting

confidence: 94%

Section: Immunohistochemistry Evaluationmentioning

confidence: 99%

The effect of simvastatin on the regeneration of surgical cavities in the femurs of rabbits

Rosselli

Martins

et al. 2014

Acta Cir. Bras.

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“…The simvastatin solution was prepared by mixing simvastatin (lot no. 0707071512; Galena, Campinas, SP, Brazil) and distilled water at a proportion of 2.2 mg/50 µl (solution 1 6 ) or of 0.5 mg/50 µl (solution 2 7 ) and centrifuging the mixture for 1 h. The animals were divided into four groups:…”

Section: Methodsmentioning

confidence: 99%

“…• local delivery in methylcellulose gel; 6,7 • local delivery in polylactic acid/polyglycolic acid copolymer; 5 • local delivery in gelatin sponge; 8 and • statins used in combination with calcium sulfate. 9,10 The results have often been encouraging.…”

Section: Introductionmentioning

confidence: 99%

Influence of the association between simvastatin and demineralized bovine bone matrix on bone repair in rats

Lima

Calixto

Anbinder³

2011

Braz. oral res.

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Simvastatin, a drug used to lower blood cholesterol, has been reported to have an anabolic effect on bone. The purpose of this study was to evaluate the influence of simvastatin and demineralized bovine bone matrix (DBBM) on the repair of rat calvarial defects. Defects of 5 mm were created in 64 rats, divided into four groups: no local treatment (control); treatment with DBBM (DBBM); treatment with a combination of simvastatin solution (2.2 mg/50 µl) and DBBM (DBBMSIM-1); and treatment with simvastatin solution (0.5 mg/50 µl) and DBBM (DBBM-SIM-2). Animals were sacrificed on postoperative day 30 or 60, after which the calvariae were X-rayed and prepared for histomorphometric evaluation. The data were submitted to statistical analysis (p < 0.05). Xrays revealed that, on postoperative day 30, animals treated with a lower dose of simvastatin presented the lowest bone density, whereas on postoperative day 60 the use of simvastatin, regardless of the dose, resulted in lower density than that observed in control and DBBM group samples. Histomorphometric analysis revealed that, on postoperative day 30, both DBBM and DBBMSIM-1 had a negative impact on bone formation. On postoperative day 60, none of the combinations tested impaired bone repair. These results showed that the association between DBBM and simvastatin had a negative impact on bone repair.

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“…The materials available for bone regeneration are still expensive and unaffordable to many patients, and therefore, there is a tireless search by the scientific community for a biomaterial that is efficient and, at the same time, accessible to the majority of the population 6,8 .…”

Section: Introductionmentioning

confidence: 99%

Behavioural and cognitive effects of simvastatin dose used in stimulation of bone regeneration in rats

Sousa¹,

Santana

Ferreira

et al. 2014

Acta Cir. Bras.

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PURPOSE:To analyze the effects of simvastatin (SVT) in the locomotion, anxiety and memory of rats, as a reflection of the administration of a minimum dose capable of stimulating bone regeneration in defects in the calvariae. METHODS:Surgical procedures were performed in 15 female Wistar rats, 2-month old, to insert the grafting material regenerator (Bone-ceramic ® ) and/or SVT, followed by behavioural and cognitive assessments in the 7 th , 30 th and 60 th days post surgery. RESULTS:The SVT locally applied with the goal of bone regeneration in defects created in rat calvariae does not interfere with locomotion, anxiety levels and/or memories of rats, except for the first week following surgery, when an anxiolytic effect was observed, as a result of a possible central action. CONCLUSION:Failure to provoke any response within 30 and 60 days post surgical procedures suggests that SVT may constitute a good choice in stimulating bone regeneration without affecting the long term neural functions.

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Local Simvastatin Effects on Mandibular Bone Growth and Inflammation

Abstract: Reducing the simvastatin dose from 2.2 to 0.5 mg reduced inflammation to a more clinically acceptable level without sacrificing bone-growth potential, but COX-associated inflammation appears to be necessary for in vivo bone growth.

Cited by 153 publications

References 32 publications

The effect of simvastatin on the regeneration of surgical cavities in the femurs of rabbits

The effect of simvastatin on the regeneration of surgical cavities in the femurs of rabbits

Influence of the association between simvastatin and demineralized bovine bone matrix on bone repair in rats

Behavioural and cognitive effects of simvastatin dose used in stimulation of bone regeneration in rats

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