Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations

Gutiérrez, Gloria; Lalka, David; Garrett, I. Ross; Rossini, Gianni; Mundy, Gregory R.

doi:10.1007/s00198-006-0079-0

Cited by 87 publications

(67 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This effect comes directly through activation of bone morphogenic protein (BMP-2) and TGF-b1 (Mundy et al, 1999;Nyan et al, 2010;Stojadinovic et al, 2010) as well as, indirectly by the suppression of osteoclast activity (Hughes et al, 2007;Ayukawa et al, 2009;Luisetto & Camozzi, 2009;Moriyama et al, 2010). Studies proved that this control of bone remodeling process by statins was prominent after subcutaneous, oral and local administration (Oxlund & Andreassen, 2004;Gutierrez et al, 2006;Moriyama et al, 2008). Local application could reduce the side effects and eliminate the doubts about the biodistribution of parenteral and oral statins to bone (Hirabayashi & Fujisaki, 2003;Miyamoto et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration

Ibrahim

Fahmy

2016

Drug Delivery

View full text Add to dashboard Cite

Objective: Statins proved potential bone healing properties. Rosuvastatin is a synthetic, hydrophilic, potent and highly efficacious statin. In the current work, an attempt was investigated to develop, evaluate various bioerodible composite sponges enclosing rosuvastatin and explore their potential in augmenting bone healing and regeneration. Method: Twelve lyophilized sponge formulae were prepared adapting a 4 1 .3 1 full factorial design. Xanthan gum, polycarbophil, Carbopol Õ and sodium alginate were investigated as anionic polymers, each at three chitosan:anionic polymer ratios (1:3, 1:1, 3:1). The formula of choice was implanted in fractured rat femora. Results: Visual and microscopic examination showed flexible homogenous porous structures with considerable bending ability. Polyelectrolyte complex formation was proved by DSC and FT-IR for all chitosan/anionic combinations except with xanthan gum where chitosan probably bound to the drug rather than xanthan gum. Statistical analysis proved that anionic polymer type and chitosan: polymer ratio, as well as, their interactions, exhibited significant effects on the release parameters at p 0.05. The optimum chitosan/anionic polymer complexation ratios were 3:1 for polycarbophil and 1:1 for Carbopol and alginate. The release at these ratios followed Fiction diffusion while other ratios had anomalous diffusion. Imwitor Õ 900K and HPMC K100M were added as release retarardants for further release optimization. The formula of choice was implanted in fractured rat femora. Histopathological examination revealed advanced stages of healing in treated femora compared to control ones. Conclusion: Biodegradable sponges for local rosuvastatin delivery proved significantly enhanced wound healing and regeneration properties to fractured bones.

show abstract

Section: Introductionmentioning

confidence: 99%

Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration

Ibrahim

Fahmy

2016

Drug Delivery

View full text Add to dashboard Cite

show abstract

“…2 Statins target the liver and have reduced affinity for bone tissue; in addition, orally administered statins are poorly distributed to bone. 3 The doses required for statins to have an effect on bone are much higher than those required to reduce cholesterol levels and are associated with unacceptable toxicity. 3 The major limitation to the clinical use of statins for bone regeneration is the lack of an effective carrier for the drug, 4 since the success of in vivo bone formation depends on high local concentrations of statins.…”

Section: Introductionmentioning

confidence: 99%

“…3 The doses required for statins to have an effect on bone are much higher than those required to reduce cholesterol levels and are associated with unacceptable toxicity. 3 The major limitation to the clinical use of statins for bone regeneration is the lack of an effective carrier for the drug, 4 since the success of in vivo bone formation depends on high local concentrations of statins. 5 Various authors have investigated new methods and carriers for the administration of statins:…”

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 vivo, the effects are even more contradictory. Although there are studies which agree with the original findings of Mundy et al (Garrett et al 2001, Oxlund et al 2001, Sugiyama and Kawai 2001, Garrett and Mundy 2002, Kajinami et al 2003, Staal et al 2003, Wong and Rabie 2003, Kawane et al 2004, Stein et al 2005, Gutierrez et al 2006, Garrett et al 2007), some very conscientiously designed studies have not been able to demonstrate any such effects (Maritz et al 2001, von Stechow et al 2003, Yao et al 2006.…”

Section: Statinsmentioning

confidence: 74%

Following the mevalonate pathway to bone heal alley

Skoglund¹

2007

Acta Orthopaedica

View full text Add to dashboard Cite

Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations

Abstract: These results show transdermal application of statins produces greater beneficial effects on bone formation than oral administration does.

Cited by 87 publications

References 31 publications

Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration

Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration

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

Following the mevalonate pathway to bone heal alley

Contact Info

Product

Resources

About