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To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> s.c.); alendronate (0.003 and 0.03\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> s.c.); raloxifene hydrochloride (0.05 and 0.5\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> s.c.); 17\u2010\u03b1\u2010ethinyl oestradiol (0.003 and 0.03\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> s.c.)) for 12 weeks. Untreated OVX (<jats:italic>n<\/jats:italic>=12) and sham OVX (<jats:italic>n<\/jats:italic>=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone\u2010alkaline phosphatase (b\u2010ALP), collagen C\u2010telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor\u2010\u03baB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Genistein (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) showed a greater increase in both BMD (<jats:italic>P<\/jats:italic>&lt;0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b\u2010ALP (<jats:italic>P<\/jats:italic>&lt;0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2008) <jats:bold>155<\/jats:bold>, 896\u2013905; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.305\">10.1038\/bjp.2008.305<\/jats:ext-link>; published online 11 August 2008<\/jats:p><\/jats:sec>","DOI":"10.1038\/bjp.2008.305","type":"journal-article","created":{"date-parts":[[2008,8,11]],"date-time":"2008-08-11T14:12:26Z","timestamp":1218463946000},"page":"896-905","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Effects of genistein aglycone in osteoporotic, ovariectomized rats: a comparison with alendronate, raloxifene and oestradiol"],"prefix":"10.1111","volume":"155","author":[{"given":"A","family":"Bitto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B P","family":"Burnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Polito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Marini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R M","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M A","family":"Armbruster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Minutoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Di Stefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Irrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Antoci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Granese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Squadrito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Altavilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2004.00068.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/cmt.5.2.190.196"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568016043477297"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100953200"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.138.11.5652"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.54.1.105"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/13697130701586113"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.5.2309"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(01)00661-5"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra067395"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-2115(98)00313-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1079\/BJN20061735"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","unstructured":"Collaborative Group on Hormonal Factors in Breast Cancer(1997).Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer. 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