MAGNESIUM AND METABOLIC BONE DISEASE IN CHRONIC LIVER DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。代谢性骨病是儿童和成人慢性肝病中一种常见且重要的并发症。在胆汁淤积期间发生的骨质减少最终导致长骨骨折，对药物治疗反应不佳，并成为许多患者肝移植的指征。最近受到关注的一个与胆汁淤积性肝病期间骨代谢相关的因素是镁稳态。镁的缺乏可能会干扰甲状旁腺激素的分泌和随后的骨矿化。据推测，膳食镁的吸收不良继发于胆汁淤积引起的脂肪漏，导致镁皂与未吸收的脂肪酸形成。镁缺乏与慢性胆汁淤积性肝病儿童的骨密度下降有关，镁的补充将与骨密度的改善有关。在其他临床情况下发生的骨形成受损的发病机制涉及其他因素；炎性细胞因子（IL-1、IL-6和TNF α）浓度升高已被证明可抑制成骨细胞的骨合成；IGF-1也有助于正常成骨细胞功能和骨增生。慢性肝病患儿血清IGF-1水平抑制已有报道。本研究的主要目的是确定慢性胆汁淤积性和非胆汁淤积性肝病患儿的循环细胞因子、IGF-1和IGF-1结合蛋白（IGFBP）与骨矿物质密度的关系。对患有胆汁淤积性和非胆汁淤积性肝病的儿童进行这些因素的评估，将有助于区分慢性胆汁淤积症与慢性肝病对骨形成的影响。一旦确诊，缺镁儿童将接受补镁治疗，并在2年内评估其对骨密度的影响。受试者将被招募为三组；胆汁淤积性肝病、非胆汁淤积性肝病和正常对照者。在缺镁的受试者中补充镁可能对代谢性骨病有治疗益处，这可能会改善肝病患者的护理。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Metabolic bone disease is a frequent and significant complication of chronic liver disease in children and adults. Osteopenia that develops during cholestasis culminates in fractures of long bones, which responds poorly to medical treatment and becomes an indication for liver transplantation in many patients. A factor related to bone metabolism during cholestatic liver disease that has recently received attention is magnesium homeostasis. A deficiency of magnesium may interfere with parathyroid hormone secretion and subsequent bone mineralization. It is postulated that dietary magnesium is malabsorbed secondary to the steatorrhea caused by cholestasis, which leads to the formation of magnesium soaps with unabsorbed fatty acids. Magnesium deficiency is associated with decreased bone mineral density in children with chronic cholestatic liver disease and that repletion with magnesium will be associated with improvement of bone mineral density. Other factors have been implicated in the pathogenesis of impaired bone formation that occurs in other clinical situations; Elevated concentrations of inflammatory cytokines (IL-1, IL-6 and TNF alpha) have been shown to inhibit osteoblast synthesis of bone; IGF-1 is also instrumental in normal osteoblast function and bone accretion. Suppressed serum levels of IGF-1 have been reported in children with chronic liver disease. A major goal of this proposal is to determine the relationship of circulating cytokines, IGF-1 and IGF-1 binding proteins (IGFBP) to bone mineral density in children with chronic cholestatic and non-cholestatic liver disease. The evaluation of these factors in children with both cholestatic and non-cholestatic liver disease will allow for the differentiation of the effects of chronic cholestasis vs. that of chronic liver disease on bone formation. Once identified, children with magnesium deficiency will undergo magnesium repletion and its effect on bone mineral density will be evaluated over 2 years. Subjects will be recruited into three groups; those with cholestatic liver disease, those with non-cholestatic liver disease, and normal controls. Repletion of magnesium in deficient subjects may have therapeutic benefit for metabolic bone disease, which may improve the care of patients with liver disease.