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

Lima, Carlos Eugênio Villaboim de Castro; Calixto, Jimmy Cavalcanti; Anbinder, Ana Lia

doi:10.1590/s1806-83242011000100008

Cited by 21 publications

(14 citation statements)

References 19 publications

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“…51 demonstrated controversial, and even negative, effects of statins on bone repair, the vast majority of the studies in Table 1 support the beneficial role of this group of drugs. The administration of statins presents anabolic effects by promoting osteoblast activity and suppressing osteoclasts.…”

Section: Experimental Studiesmentioning

confidence: 99%

Statins, bone formation and osteoporosis: hope or hype?

Tsartsalis¹,

Dokos²,

Kaiafa³

et al. 2012

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Osteoporosis is a major health problem affecting both men and women. statins, besides their action as lipid-lowering agents, seem to have additional pleiotropic properties, among them a beneficial effect on bone mineral density. the entirety of experimental and the majority of clinical studies as well as the only relevant meta-analysis suggest that statins have an anabolic effect on bone metabolism. statins, osteoporosis and adipogenesis share the same pathway, rANKL/OPG. It would appear that an imbalance in this pathway could be responsible for the manifestation of some metabolic disorders such as diabetes mellitus, atherogenesis, multiple myeloma, osteoporosis. Possibly in the future, drugs which can intervene in this biochemical and pathophysiological cascade, like statins, in a variety of doses, could be used for the management of ectopic ossification syndromes and other bone disorders, even as an additive treatment. Until then, further large longitudinal randomized controlled studies for each statin separately are required to confirm this hypothesis.

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Section: Experimental Studiesmentioning

confidence: 99%

Statins, bone formation and osteoporosis: hope or hype?

Tsartsalis¹,

Dokos²,

Kaiafa³

et al. 2012

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“…25,35,38 It has been shown that low dose of Simvastatin (0.5 mg) reduces bone density on day 30 while after 60 days of injury, regardless of the dose, Simvastatin both at 0.5 and 2.2 mg/rat BW retards bone healing. 58 In rabbits, 2.5 and 5 mg Simvastatin/scaffold or/rabbit BW were the most effective doses responsible for bone regeneration. 38,92 In mice, 0.6 to 1 lmol/L and also 2.2 mg/scaffold or/mouse BW were effective in bone healing.…”

Section: Dosementioning

confidence: 97%

“…Impregnation of bone scaffolds with Simvastatin is the simplest way, but because the drug has high delivery rate (burst release effect) in the injured area, most of the drug is dissolved in the blood circulation and removed from the body so that the bioavailability of the drug is too short to be effective in influencing the reparative and remodelling phase of bone healing. 58,60 Alternatively, Simvastatin can be coated on the bone scaffolds by various methods such as spray techniques and ultrasonic dispersion. 1,113 However, in this method only low concentrations of Simvastatin can be coated and thus, the drug availability is more valuable in the inflammatory phase of bone healing and cannot be increased in order to influence later stages (e.g.…”

Section: Drug Delivery Systems Used In Simvastatin Therapymentioning

confidence: 99%

Role of Simvastatin on fracture healing and osteoporosis: a systematic review onin vivoinvestigations

Moshiri

Sharifi

Oryan

2016

Clin Exp Pharma Physio

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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.

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“…Some authors did not observe new bone formation induced by simvastatin [22][23][24] . Other reports indicate that simvastatin 17,[25][26][27][28] influenced and stimulated new bone formation.…”

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

Cited by 21 publications

References 19 publications

Statins, bone formation and osteoporosis: hope or hype?

Statins, bone formation and osteoporosis: hope or hype?

Role of Simvastatin on fracture healing and osteoporosis: a systematic review onin vivoinvestigations

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

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