HOMOCYSTEINEMIA--A RISK FACTOR FOR OSTEOPOROSIS

同型半胱氨酸血症——骨质疏松症的危险因素

• 批准号: 2131706
• 负责人: CHARLES W PRINCE
• 金额: $ 2.14万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2131706
• 关键词: SDS polyacrylamide gel electrophoresis; aminoacid metabolism; biomarker; blood chemistry; bone marrow; cell cycle; disease /disorder prevention /control; disease /disorder proneness /risk; extracellular matrix; growth media; homeostasis; homocysteine; homocystinuria; laboratory rat; musculoskeletal disorder diagnosis; normal ossification; osteoclasts; osteocytes; osteogenesis; osteoporosis; pathologic bone resorption; tissue /cell culture

Osteoporosis, a chronic disease causing significant morbidity among an increasingly large population, is difficult to diagnose and treat. An important goal is prevention of osteoporosis, though its multi-factorial etiology has prevented elucidation of all its causes. Homocystinuria, an inborn error of metabolism resulting from deficient cystathionine beta- synthase activity, is characterized by elevated homocysteine levels in blood and early onset of severe osteoporosis of the spine and long bones. The probability of homocysteinemia, in the absence of a genetic disease, increases with age and after menopause and may result from several factors: nutrient deficiencies (vitamin B6 and folic acid), malabsorption (due to vitamin B12 deficiency, excess alcohol intake or non-steroidal anti-inflammatory drug use), a high methionine diet (i.e., a high animal protein diet) and/or unknown factors. Thus, it is our hypothesis that elevated levels of homocysteine represent another risk factor for osteoporosis. We shall investigate the effects of elevated homocysteine on bone cell growth, extracellular matrix synthesis, bone formation and bone resorption by using an in vitro approach. Rat bone marrow cells, under the appropriate culture conditions, can be induced to make bone or to produce active osteoclasts. We shall add exogenous homocysteine or cause the cells to produce elevated levels of homocysteine (by imposing nutrient deficiencies) and assay effects on the parameters named above. Thus, we shall be able to assess the effects of elevated homocysteine on the two components of bone homeostasis, formation and resorption, at functional levels. If data supporting our hypothesis are obtained, we shall undertake a cross-sectional study of plasma homocysteine levels in elderly people with and without osteoporosis and, ultimately, for an intervention trial in which dietary strategies are used to lower homocysteine levels.

骨质疏松症是一种慢性疾病， 越来越多的人口，很难诊断和治疗。 一个重要目标是预防骨质疏松症，尽管其多因素 病因学阻碍了对其所有原因的阐明。同型胱氨酸尿症 先天性代谢缺陷，由缺乏胱硫醚β- 合成酶活性，其特征是高半胱氨酸水平升高， 血液和脊椎和长骨的严重骨质疏松症的早期发作。 在没有遗传疾病的情况下， 随着年龄的增长和绝经后增加，可能是由于几个 因素：营养缺乏（维生素B6和叶酸），吸收不良 (due维生素B12缺乏、过量饮酒或非甾体类 抗炎药物使用），高蛋氨酸饮食（即，高等动物 蛋白质饮食）和/或未知因素。因此，我们假设， 同型半胱氨酸水平升高是另一个危险因素， 骨质疏松 我们将研究升高的同型半胱氨酸对骨细胞的影响， 生长、细胞外基质合成、骨形成和骨吸收 by using运用an in vitro体外approach方法. 大鼠骨髓细胞， 在适当的培养条件下，可以诱导成骨或产生 活性破骨细胞 我们应该加入外源性同型半胱氨酸， 细胞产生高水平的同型半胱氨酸（通过施加营养 缺陷）和测定对上述参数的影响。 因此我们 应能够评估同型半胱氨酸升高对两个 骨稳态、形成和再吸收的组成部分，在功能 程度. 如果获得了支持我们假设的数据，我们将进行一项 老年人血浆同型半胱氨酸水平的横断面研究 没有骨质疏松症，最终， 哪些饮食策略可以降低同型半胱氨酸水平。