MAGNESIUM AND METABOLIC BONE DISEASE IN CHRONIC LIVER DISEASE

慢性肝病中的镁与代谢性骨病

• 批准号: 7374321
• 负责人: MICHAEL R. NARKEWICZ
• 金额: $ 0.49万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-24 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374321
• 关键词: bone; bone density; children; cholestasis; liver; magnesium

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.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。代谢性骨病是儿童和成人慢性肝病的常见和重要并发症。在胆汁淤积期间发生的骨量减少最终会导致长骨骨折，这对药物治疗的反应很差，并成为许多患者进行肝移植的适应症。最近受到关注的一个与胆汁淤积性肝病期间的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，饮食中的镁被吸收不良继发于胆汁淤积引起的脂肪泻，从而导致镁肥皂的形成，其中含有未被吸收的脂肪酸。在慢性淤胆性肝病的儿童中，镁缺乏与骨密度降低有关，而镁的补充将与骨密度的改善有关。其他因素也参与了其他临床情况下骨形成障碍的发病机制；炎性细胞因子(IL-1、IL-6和TNFα)浓度的升高被证明抑制了成骨细胞的骨合成；IGF-1也有助于正常的成骨细胞功能和骨的生长。有报道称，慢性肝病儿童的血清IGF-1水平受到抑制。这项建议的一个主要目标是确定慢性淤胆性和非淤胆性肝病儿童循环细胞因子、IGF-1和IGF-1结合蛋白(IGFBP)与骨密度的关系。在胆汁淤积性和非胆汁淤积性肝病的儿童中评估这些因素将有助于区分慢性胆汁淤积症和慢性肝病对骨形成的影响。一旦确诊，缺镁儿童将接受镁补充，其对骨密度的影响将在两年内进行评估。受试者将被招募到三组：胆汁淤积性肝病组、非胆汁淤积性肝病组和正常对照组。在缺乏镁的受试者中补充镁可能对代谢性骨病有治疗作用，这可能会改善肝病患者的护理。