Effects of Simvastatin Gels on Murine Calvarial Bone

Thylin, Michael R.; McConnell, Jay C.; Schmid, Marian J.; Reckling, Ryon R.; Ojha, Junu; Bhattacharyya, Indraneel; Marx, David B.; Reinhardt, Richard

doi:10.1902/jop.2002.73.10.1141

Cited by 135 publications

(154 citation statements)

References 32 publications

Supporting

Mentioning

137

Contrasting

Unclassified

Order By: Relevance

“…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%

See 1 more Smart Citation

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

Rosselli

Martins

et al. 2014

Acta Cir. Bras.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 94%

“…Other reports indicate that simvastatin 17,[25][26][27][28] influenced and stimulated new bone formation. There are few consistent studies on the anabolic effects and bioavailability of simvastatin, which is a fact that leads to such varying results among several studies 29 .…”

Section: Immunohistochemistry Evaluationmentioning

confidence: 94%

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

Rosselli

Martins

et al. 2014

Acta Cir. Bras.

View full text Add to dashboard Cite

show abstract

“…4 In the present study, the use of high local doses of simvastatin caused an intense inflammatory reaction, accompanied by tissue necrosis and scabbing. Soft tissue inflammation was also reported by Thylin et al, 6 who used 2.2 mg of the drug in methylcellulose gel in rat calvaria; by Nyan et al, 9 who used 1 mg of the drug in calcium sulfate in rat calvaria; and by Stein et al, 7 who used doses of 0.5, 1.0, 1.5, and 2.2 mg of the drug in rat mandible. In the study conducted by Stein et al, 7 the 0.5-mg dose presented the best cost-benefit ratio, promoting significant bone formation and reduced inflammation.…”

Section: Discussionmentioning

confidence: 61%

“…• 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.

View full text Add to dashboard Cite

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.

show abstract

“…In addition, implant insertion was in the present study mono-cortical while Du et al performed bi-cortical insertion. Since the successful local application of statins has been demonstrated to depend on an effective drug delivery system, like chitosan, PGA or methylcellulose gels (Thylin et al, 2002), we have utilised chitosan in the present study. In accordance with previous studies, we observed a transient increase in BIC and the amount of peri-implant bone in the group that had received statin coated implants.…”

Section: B Stadlinger Et Al Modified Implants In An Osteoporosis Modelmentioning

confidence: 99%

Osseointegration of biochemically modified implants in an osteoporosis rodent model

Stadlinger

Korn

Tödtmann

et al. 2013

eCM

View full text Add to dashboard Cite

The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control) or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX) osteoporotic rats (n = 32/group). In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout). Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC), periimplant bone area (BA), bone volume/tissue volume (BV/ TV) and bone-mineral density (BMD) in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

show abstract

Effects of Simvastatin Gels on Murine Calvarial Bone

Abstract: A single, high dose of simvastatin gel can stimulate murine cranial bone apposition, particularly when delivered under an occlusive membrane. Both approaches should be investigated further for possible development for periodontal therapy.

Cited by 135 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

Osseointegration of biochemically modified implants in an osteoporosis rodent model

Contact Info

Product

Resources

About