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Vehicle or <jats:styled-content style=\"fixed-case\">RLX<\/jats:styled-content> was administered orally for 90\u00a0days. During treatment, the dental pulp of mandibular first molars was exposed to the oral environment for induction of periapical lesions, which were analysed after 7 and 30\u00a0days. After the experimental periods, blood samples were collected for measurement of oestradiol, calcium, phosphorus and alkaline phosphatase. The rats were euthanized and the mandibles removed and processed for immunohistochemical detection of receptor activator of nuclear factor kappa\u2010B ligand (<jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>), osteoprotegerin (<jats:styled-content style=\"fixed-case\">OPG<\/jats:styled-content>), hypoxia\u2010inducible factor\u20101 alpha (<jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1) and bone\u2010specific alkaline phosphatase (<jats:styled-content style=\"fixed-case\">BALP<\/jats:styled-content>). Data were compared using Kruskal\u2013Wallis followed by Dunn test (nonparametric values) and <jats:sc>anova<\/jats:sc> followed by the Tukey's test (parametric values).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The plasma concentration of oestradiol showed hypo\u2010oestrogenism in the rats subjected to ovary removal. On day 7, alkaline phosphatase activity, calcium and phosphorus were higher in the <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">RLX<\/jats:styled-content> group than in the <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u2010veh group (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), but immunolabelling for <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 was lower in <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">RLX<\/jats:styled-content> group (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). On day 30, the <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u2010veh group had higher immunolabelling for <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content> than the <jats:styled-content style=\"fixed-case\">OVX<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">RLX<\/jats:styled-content> group (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). There were no significant differences in the immunoreactivity of <jats:styled-content style=\"fixed-case\">OPG<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">BALP<\/jats:styled-content> between any groups at either time\u2010point (<jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">RLX<\/jats:styled-content> therapy reversed the increased levels of the local regulators of both osteoclastogenesis and angiogenesis induced by oestrogen deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.12403","type":"journal-article","created":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T15:35:28Z","timestamp":1414596928000},"page":"1059-1068","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Raloxifene modulates regulators of osteoclastogenesis and angiogenesis in an oestrogen deficiency periapical lesion model"],"prefix":"10.1111","volume":"48","author":[{"given":"J. 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