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  1. Moshiri A, Sharifi AM, Oryan A
    Clin Exp Pharmacol Physiol, 2016 Jul;43(7):659-84.
    PMID: 27061579 DOI: 10.1111/1440-1681.12577
    Simvastatin 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.
  2. Moshiri A, Tekyieh Maroof N, Mohammad Sharifi A
    Iran J Basic Med Sci, 2020 Nov;23(11):1426-1438.
    PMID: 33235700 DOI: 10.22038/ijbms.2020.46228.10707
    Objectives: We investigated the role of various biomaterials on cell viability and in healing of an experimentally induced femoral bone hole model in rats.

    Materials and Methods: Cell viability and cytotoxicity of gelatin (Gel; 50 µg/µl), chitosan (Chi; 20 µg/µl), hydroxyapatite (HA; 50 µg/µl), nanohydroxyapatite (nHA; 10 µg/µl), three-calcium phosphate (TCP; 50 µg/µl) and strontium carbonate (Sr; 10 µg/µl) were evaluated on hADSCs via MTT assay. In vivo femoral drill-bone hole model was produced in rats that were either left untreated or treated with autograft, Gel, Chi, HA, nHA, TCP and Sr, respectively. The animals were euthanized after 30 days. Their bone holes were evaluated by gross-pathology, histopathology, SEM and radiography. Also, their dry matter, bone ash and mineral density were measured.

    Results: Both the Gel and Chi showed cytotoxicity, while nHA had no role on cytotoxicity and cell-viability. All the HA, TCP and Sr significantly improved cell viability when compared to controls (P<0.05). Both the Gel and Chi had no role on osteoconduction and osteoinduction. Compared to HA, nHA showed superior role in increasing new bone formation, mineral density and ash (P<0.05). In contrast to HA and nHA, both the TCP and Sr showed superior morphological, radiographical and biochemical properties on bone healing (P<0.05). TCP and Sr showed the most effective osteoconduction and osteoinduction, respectively. In the Sr group, the most mature type of osteons formed.

    Conclusion: Various biomaterials have different in vivo efficacy during bone regeneration. TCP was found to be the best material for osteoconduction and Sr for osteoinduction.

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