ROLE OF HYPERBILIRUBINEMIA IN THE IMPAIRMENT OF OSTEOBLAST PROLIFERATION-ASSOCIATED WITH CHOLESTATIC JAUNDICE
ROLE OF HYPERBILIRUBINEMIA IN THE IMPAIRMENT OF OSTEOBLAST PROLIFERATION-ASSOCIATED WITH CHOLESTATIC JAUNDICE
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DOI：
10.1172/jci117959
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发表时间：
1995-06-01
影响因子：
15.9
通讯作者：
RIGGS, BL
中科院分区：
文献类型：
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作者：
JANES, CH;DICKSON, ER;RIGGS, BL
由于慢性胆汁淤积性肝病（CCLD）中发生的骨质疏松症与骨形成减少有关，并且通过肝移植是可逆的，胆汁淤积期间保留在血浆中的物质可能损害成骨细胞功能。29例年龄、性别相匹配的正常人的平均PMA为56.4%（P < 0.001），14例CCLD和15例其他黄疸患者的PMA下降幅度相似。胆汁酸和胆红素是胆汁淤积期间保留的两大类产物。将普通结合胆汁酸和胆红素以模拟CCLD患者中发现的浓度加入正常人血浆中。各种胆汁盐对PMA无影响，而非结合胆红素以剂量依赖方式降低PMA（r =-0.98，P < 0.0001）在不影响细胞活力的情况下，通过光漂白从血浆中相对选择性地去除胆红素使5名黄疸患者的PMA降低正常化，但在5名正常受试者中没有产生明显变化，这些数据支持高胆红素血症或其他可能的光不稳定物质损害成骨细胞增殖能力的假设，因此可能在与CCLD相关的骨质疏松症的发病机制中发挥重要作用。
Because the osteoporosis occurring in chronic cholestatic liver disease (CCLD) is associated with decreased bone formation and is reversible by liver transplantation, substances retained in plasma during cholestasis may impair osteoblast function, This hypothesis was tested using a new bioassay that measures plasma mitogenic activity (PMA) for normal human osteoblast-like (hOB) cells, In 29 jaundiced patients, mean PMA was 56.4% (P < 0.001) of that in 29 age- and sex-matched normal subjects, and the decrease in PMA was similar in the 14 with CCLD and the 15 with other causes of jaundice. Bile acids and bilirubin are the two major groups of products retained during cholestasis. The common conjugated bile acids and bilirubin were added to normal human plasma in concentrations simulating those found in patients with CCLD. Various bile salts had no effect on PMA whereas unconjugated bilirubin decreased PMA in a dose-dependent fashion (r = -0.98, P < 0.0001) without affecting cell viability, Relatively selective removal of bilirubin from the plasma by photobleaching normalized the decreased PMA in five jaundiced patients but produced no apparent change in five normal subjects, These data support the hypothesis that hyperbilirubinemia or possibly other photolabile substances impair osteoblast proliferative capacity and thus may play a major role in the pathogenesis of the osteoporosis associated with CCLD.