{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T19:51:49Z","timestamp":1778701909510,"version":"3.51.4"},"reference-count":59,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2008,8,7]],"date-time":"2008-08-07T00:00:00Z","timestamp":1218067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Simvastatin, an inhibitor of 3\u2010hydroxy\u20103\u2010methylglutaryl coenzyme A reductase, is a cholesterol\u2010lowering drug that may play a role in bone metabolism through a mechanism that is not fully understood. Recently, receptor activator of NF\u2010\u03baB ligand (RANKL), a member of the TNF superfamily, has emerged as a major mediator of bone loss <jats:italic>via<\/jats:italic> activation of osteoclastogenesis. The latter is also associated with certain cancers such as multiple myeloma and breast cancer. Whether simvastatin can modulate RANKL\u2010induced or cancer induced osteoclastogenesis was investigated. The effect of simvastatin on RANKL signaling and consequent osteoclastogenesis was investigated. RANKL induced NF\u2010\u03baB activation, whereas pretreatment with simvastatin completely suppressed such activation and correlated with suppression of RANKL\u2010induced activation of I\u03baB\u03b1 kinase, I\u03baB\u03b1 phosphorylation and I\u03baB\u03b1 degradation. Similarly, RANKL induced the differentiation of monocytic cells to osteoclasts, whereas simvastatin suppressed it. The inhibition was maximal when cells were exposed to both simvastatin and RANKL simultaneously and minimal when simvastatin was added 1 day after RANKL treatment. Simvastatin also inhibited the osteoclastogenesis induced by human breast cancer and by multiple myeloma cells. Together, our results indicate that simvastatin inhibits the RANKL\u2010induced NF\u2010\u03baB activation pathway that leads to suppression of osteoclastogenesis induced by RANKL and by tumor cells, thereby suggesting its therapeutic potential in osteoporosis and in cancer\u2010related bone loss. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23745","type":"journal-article","created":{"date-parts":[[2008,8,7]],"date-time":"2008-08-07T19:35:05Z","timestamp":1218137705000},"page":"1733-1740","source":"Crossref","is-referenced-by-count":109,"title":["Simvastatin, 3\u2010hydroxy\u20103\u2010methylglutaryl coenzyme A reductase inhibitor, suppresses osteoclastogenesis induced by receptor activator of nuclear factor\u2010\u03baB ligand through modulation of NF\u2010\u03baB pathway"],"prefix":"10.1002","volume":"123","author":[{"given":"Kwang 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