Can low doses of simvastatin enhance fracture healing? An experimental study in rabbits

Chissas, D.; Ntagiopoulos, Panagiotis G.; Stamatopoulos, G.; Verettas, D.; Kazakos, Konstantinos; Papalois, A.; Agrogiannis, Georgios; Papaeliou, A.; Agapitos, E.; Balanika, Alexia; Papadopoulou, E.; Anastopoulos, G.; Asimakopoulos, A.

doi:10.1016/j.injury.2009.07.024

Cited by 6 publications

(7 citation statements)

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“…Local application of a nanobead preparation of lovastatin was also shown to be beneficial in hastening fracture healing in rats [59]. However, orally administered simvastatin at 10 and 30 mg/kg/day had a negative anabolic effect on callus formation in rabbits' fracture healing, whereas lower doses did not show any effect in the early stages of fracture healing [60]. Research conducted so far indicates that lipophilic statins are more effective in enhancing the bone healing.…”

Section: Statins and Bone Healingmentioning

confidence: 99%

Statins as potential therapeutic agents for healing disorders

Stojadinović

Lebrun

Pastar

et al. 2010

Expert Review of Dermatology

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Statins, HMG-CoA reductase inhibitors, are common cholesterol-lowering drugs. Recent studies suggest that statins may have potential as novel treatments for diverse conditions, ranging from sepsis and inflammatory diseases to chronic wounds and bone fractures. The diverse pleiotropic actions of statins are probably related to reduced isoprenylation of downstream targets of the mevalonate pathway and their binding to several nuclear hormone receptors. Statins exert their anti-inflammatory effect by inhibiting the release of C-reactive peptide, chemokines, cytokines and adhesion molecules, which may make them a powerful addition to the dermatologic antiinflammatory medication arsenal. Along with reducing inflammation, statins have the potential to heal chronic wounds by decreasing farnesyl pyrophosphate, facilitating vascular relaxation, promoting neovascularization and reducing bacterial load. A review of the literature elucidates that route of administration, dose and type of statin appear to impact the outcome. A better understanding of their effects at the cellular and molecular level in skin is necessary for their future use.

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Section: Statins and Bone Healingmentioning

confidence: 99%

Statins as potential therapeutic agents for healing disorders

Stojadinović

Lebrun

Pastar

et al. 2010

Expert Review of Dermatology

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“…16 Controversial effects of simvastatin on bone formation have also been reported. 15,33 Maritz et al indicated that oral administration of high-dose simvastatin (20 mg/kg/day) increases bone formation and resorption, while low-dose simvastatin (1 mg/kg/day) decreases bone formation and increases bone resorption in rats. 15 In one clinical study, simvastatin 40 mg/day for one year significantly increased bone mineral density at the lumbar spine and femoral neck.…”

Section: Discussionmentioning

confidence: 99%

Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair

Tai¹,

Fu²,

Wang³

et al. 2013

IJN

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“…In rabbits, oral administration of Simvastatin with doses ranging from 10 to 30 mg/kg per day and dosages ranging from 150 to 900 mg had no beneficial effects on bone healing and to some extent such concentrations retarded bone healing and accelerated bone loss. 66,89 Higher doses particularly 120 mg/kg per day with the total dose of 10080 mg, seem to be effective in bone regeneration when Simvastatin is given orally in rabbits. 85 In canine, oral Simvastatin with the dose of 40 mg/kg per day and total dose of 3360 mg seems to be an effective approach in repairing osteonecrosis.…”

Section: Dose and Dosage Of Simvastatin In Maxillofacial Modelsmentioning

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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Can low doses of simvastatin enhance fracture healing? An experimental study in rabbits

Cited by 6 publications

References 0 publications

Statins as potential therapeutic agents for healing disorders

Statins as potential therapeutic agents for healing disorders

Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair

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

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