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Both bilirubin and lithocholic acid (LCA) result in detrimental effects on osteoblastic cells, and ursodeoxycholic acid (UDCA) counteracts these outcomes. However, there is no information on the consequences of these retained substances of cholestasis and sera from cholestatic patients in osteocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The impact of bilirubin, LCA, UDCA and serum from jaundiced patients on viability, differentiation, mineralization and apoptosis has been assessed in MLO\u2010Y4 and MLO\u2010A5 osteocyte cell lines. Effects on gene expression were assessed in these cells and in human bone fragments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lithocholic acid 10\u00a0\u03bcmol\/L and bilirubin 50\u00a0\u03bcmol\/L decreased viability in MLO\u2010Y4 and MLO\u2010A5 cells (11% and 53% respectively; <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a0.01). UDCA alone or combined with LCA or bilirubin increased cell viability. Jaundiced sera decreased cell viability (56%), an effect which was reverted by UDCA. Bilirubin decreased differentiation by 47% in MLO\u2010Y4 (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a0.01) and mineralization (87%) after 21\u00a0days in MLO\u2010A5 (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a0.03). Both bilirubin and LCA increased apoptosis in MLO\u2010Y4, and UDCA diminished the apoptotic effect. Moreover, bilirubin down\u2010regulated <jats:italic>RUNX2<\/jats:italic> and up\u2010regulated <jats:italic>RANKL<\/jats:italic> gene expression in bone tissue, MLO\u2010Y4 and MLO\u2010A5 cells, and LCA up\u2010regulated <jats:italic>RANKL<\/jats:italic> expression in bone tissue. UDCA 100\u00a0\u03bcmol\/L increased the gene expression of all these genes in bone tissue and MLO\u2010Y4 cells and neutralized the decreased <jats:italic>RUNX2<\/jats:italic> expression induced by bilirubin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Bilirubin and LCA have damaging consequences in osteocytes by decreasing viability, differentiation and mineralization, increasing apoptosis and modifying gene expression, effects that are neutralized by UDCA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14630","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T14:18:31Z","timestamp":1596550711000},"page":"2767-2775","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Bilirubin and bile acids in osteocytes and bone tissue. Potential role in the cholestatic\u2010induced osteoporosis"],"prefix":"10.1111","volume":"40","author":[{"given":"Silvia","family":"Ruiz\u2010Gasp\u00e0","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Barcelona Spain"},{"name":"Metabolic Bone Diseases Unit Department of Rheumatology Hospital Cl\u00ednic University of Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7103-9530","authenticated-orcid":false,"given":"N\u00faria","family":"Gua\u00f1abens","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Barcelona Spain"},{"name":"Metabolic Bone Diseases Unit Department of Rheumatology Hospital Cl\u00ednic University of Barcelona Barcelona 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