Topical Application of Slow-Release Simvastatin as a Bone Substitute in Bone Defects in the Rat Tibia: A Pilot Study

Rushinek, Heli; Alterman, Michael; Laviv, Amir; Weiss, Ervin I.; Friedman, Michael; Casap, Nardy

doi:10.11607/jomi.te60

Cited by 3 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These articles compare the non-introduction of filling material [9,10,12,15,16,20], and the introduction of phosphate-buffered saline [14,15,16,17,18,19], polylactic acid [8,12], collagen sponges [9,16,21], hyaluronic acid [11], polyethylene glycol [11,18], gelatin hydrogel [13,16,22] or hydroxypropyl methylcellulose [17], with the introduction into the defect area of preparations containing statins [8,22].…”

Section: Resultsmentioning

confidence: 99%

“…The statin used and the dose were different depending on the study, with simvastatin being the most employed [8,9,10,12,13,16,17,19,20], followed by lovastatin [11,14,18,22]. Rosuvastatin [15,21] was used in only two of the articles.…”

Section: Resultsmentioning

confidence: 99%

“…In all the works [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22], the filling material was introduced at the time of the bone defect creation, except for one, in which a parallel experiment was carried out, in which the injections were made at the time of surgery, and at 14, 28 and 42 days [18].…”

Section: Resultsmentioning

confidence: 99%

“…In three studies, osteoblast levels were analyzed. In one, density was evaluated [13], obtaining a significant increase in the intervention group; in another, the percentage of surface covered with osteoblasts was measured [17], without finding significant differences between both groups. In the last one, the number of osteoblasts in a given area was counted, obtaining a significantly higher value in the intervention group [19].…”

Section: Resultsmentioning

confidence: 99%

“…Studies analyzing the effect of statins on the regeneration of non-periodontal bone defects are still mostly in the preclinical phase, and evaluate radiological, histological and analytical parameters to assess their impact [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Application of Statins in the Regeneration of Bone Defects. Systematic Review and Meta-Analysis

et al. 2019

View full text Add to dashboard Cite

This systematic review aims to analyze the effect of the local application of statins in the regeneration of non-periodontal bone defects. A systematic study was conducted with the Pubmed/Medline, Embase, Cochrane Library and Scielo databases for in vivo animal studies published up to and including February 2019. Fifteen articles were included in the analysis. The local application of the drug increased the percentage of new bone formation, bone density, bone healing, bone morphogenetic protein 2, vascular endothelial growth factor, progenitor endothelial cells and osteocalcin. Meta-analyses showed a statistically significant increase in the percentage of new bone formation when animals were treated with local statins, in contrast to the no introduction of filling material or the introduction of polylactic acid, both in an early (4–6 weeks) and in a late period (12 weeks) (mean difference 39.5%, 95% confidence interval: 22.2–56.9, p <0.001; and mean difference 43.3%, 95% confidence interval: 33.6–52.9, p < 0.001, respectively). Basing on the animal model, the local application of statins promotes the healing of critical bone size defects due to its apparent osteogenic and angiogenic effects. However, given the few studies and their heterogenicity, the results should be taken cautiously, and further pilot studies are necessary, with radiological and histological evaluations to translate these results to humans and establish statins’ effect.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Application of Statins in the Regeneration of Bone Defects. Systematic Review and Meta-Analysis

et al. 2019

View full text Add to dashboard Cite

show abstract

Role of Simvastatin on fracture healing and osteoporosis: a systematic review on in vivo investigations

Moshiri

Sharifi

Oryan

2016

Clin Exp Pharma Physio

View full text Add to dashboard Cite

SUMMARYSimvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. Several in vivo studies evaluated its role on osteoporosis and fracture healing, however, controversial results are seen in the literature. For this reason, Simvastatin has not been the focus of any clinical trials as yet. This systematic review clears the mechanisms of action of Simvastatin on bone metabolism and focuses on in vivo investigations that have evaluated its role on osteoporosis and fracture repair to find out (i) whether Simvastatin is effective on treatment of osteoporosis and fracture repair, and (ii) which of the many available protocols may have the ability to be translated in the clinical setting. Simvastatin induces osteoinduction by increasing osteoblast activity and differentiation and inhibiting their apoptosis. It also reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts and their differentiation. Controversial results between the in vivo studies are mostly due to the differences in the route of administration, dose, dosage and carrier type. Local delivery of Simvastatin through controlled drug delivery systems with much lower doses and dosages than the systemic route seems to be the most valuable option in fracture healing. However, systemic delivery of Simvastatin with much higher doses and dosages than the clinical ones seems to be effective in managing osteoporosis. Simvastatin, in a particular range of doses and dosages, may be beneficial in managing osteoporosis and fracture injuries. This review showed that Simvastatin is effective in the treatment of osteoporosis and fracture healing.

show abstract

Repairing a critical cranial defect using WISP1-pretreated chondrocyte scaffolds

et al. 2023

Self Cite

View full text Add to dashboard Cite

In cranial flat bone fractures, spontaneous bone repair will occur only when the fracture ends are in close contact. However, in cases wherein bone discontinuity is extensive, surgical interventions are often required. To this end, autologous bone is harvested and surgically integrated into the site of fracture. Here we propose to use cartilage, as an alternative autologous source, to promote cranial fracture repair. The advantage of this approach is the potential reduction in donor site morbidity, likely due to the avascular and aneural nature of cartilage. As a first step we attempted to induce cartilage mineralization in vitro, using micromass primary chondrocyte cultures, incubated with BMP2 and/or WISP1, which were examined histologically following a 3-week culture period. Next, chondrocyte seeded collagen scaffolds were evaluated in vitro for expression profiles and ALP activity. Finally, chondrocyte-seeded collagen scaffolds were implanted in a Lewis rats 8 mm critical calvaria defect model, which was imaged via live CT for 12 weeks until sacrifice. End points were analyzed for microCT, histology, and serum levels of bone related markers. Micromass cultures exhibited an osseous inducing trend following WISP1 administration, which was maintained in chondrocyte seeded scaffolds. Accordingly, in vivo analysis was carried out to assess the impact of WISP1-pretreated chondrocytes (WCS) versus untreated chondrocytes (UCS) in calvaria defect model and compared to untreated control comprised of a defect-associated blood clot (BC) or empty collagen scaffold (CS) implant. Live CT and microCT exhibited higher mineralization volumes in critical defect implanted with UCS, with some structural improvements in WCS. Histological analysis exhibited higher anabolic bone formation in WCS and trabecular bone was detected in WCS and UCS groups. Chondrocytes implanted into critical cranial defect expedite the formation of native-like osseous tissue, especially after WISP1 priming in culture. Ultimately, these data support the use of autologous chondrocytes to repair critical maxillofacial defects.

show abstract

Topical Application of Slow-Release Simvastatin as a Bone Substitute in Bone Defects in the Rat Tibia: A Pilot Study

Cited by 3 publications

References 0 publications

The Application of Statins in the Regeneration of Bone Defects. Systematic Review and Meta-Analysis

The Application of Statins in the Regeneration of Bone Defects. Systematic Review and Meta-Analysis

Role of Simvastatin on fracture healing and osteoporosis: a systematic review on in vivo investigations

Repairing a critical cranial defect using WISP1-pretreated chondrocyte scaffolds

Contact Info

Product

Resources

About