{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:17:23Z","timestamp":1787501843280,"version":"build-2736575974"},"reference-count":125,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T00:00:00Z","timestamp":1466553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Simvastatin is a lipid lowering drug whose beneficial role on bone metabolism was discovered in 1999. Several\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    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\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    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\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1111\/1440-1681.12577","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T13:43:56Z","timestamp":1460295836000},"page":"659-684","source":"Crossref","is-referenced-by-count":49,"title":["Role of Simvastatin on fracture healing and osteoporosis: a systematic review on\n                    <i>in\u00a0vivo<\/i>\n                    investigations"],"prefix":"10.1111","volume":"43","author":[{"given":"Ali","family":"Moshiri","sequence":"first","affiliation":[{"name":"RAZI Drug Research Centre School of Medicine Iran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Mohammad","family":"Sharifi","sequence":"additional","affiliation":[{"name":"RAZI Drug Research Centre School of Medicine Iran University of Medical Sciences Tehran Iran"},{"name":"Department of Pharmacology School of Medicine Iran University of Medical Sciences Tehran Iran"},{"name":"Tissue Engineering Group Department of Orthopaedic Surgery (NOCERAL) Faculty of Medicine University of Malaya Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Oryan","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Veterinary Medicine Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,22]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.07.022"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-015-9981-9"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5446.1946"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1749-799X-9-18"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.35499"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0102-865020150050000003"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2015.08.034"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.892247"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MJT.0000000000000271"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977194.2015.1011270"},{"key":"e_1_2_5_12_1","first-page":"7231","article-title":"Combination of calcium sulfate and simvastatin\u2010controlled release microspheres enhances bone repair in critical\u2010sized rat calvarial bone defects","volume":"10","author":"Fu YC","year":"2015","journal-title":"Int. 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