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，一种慢性疾病 人口越来越大，难以诊断和治疗。 一个 重要目标是预防骨质疏松症，尽管其多因素 病因已经阻止了所有原因的阐明。同囊尿症，an 由于缺乏胱淀粉β-导致代谢的天生错误 合酶活性的特征是同型半胱氨酸水平升高 血液和脊柱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，同囊血症的可能性 随着年龄的增长和更年期之后的增加，可能是由几个 因素：营养缺乏症（维生素B6和叶酸），吸收不良 （由于维生素B12缺乏，过量酒精摄入或非甾体类药物 抗炎药的使用），高蛋氨酸饮食（即高动物 蛋白质饮食）和/或未知因素。因此，正是我们的假设 同型半胱氨酸的水平升高代表了另一个风险因素 骨质疏松症。 我们将研究升高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 通过使用体外方法。 大鼠骨髓细胞，在 适当的培养条件可以诱使骨骼或产生 活性破骨细胞。 我们将添加外源性同型半胱氨酸或引起 细胞产生升高的同型半胱氨酸水平（通过施加营养 缺陷）和测定对上述参数的影响。 因此，我们 应能够评估升高同型半胱氨酸对两者的影响 骨体内平衡，形成和吸收的成分，功能 水平。 如果获得了支持我们假设的数据，我们将承担 老年人血浆同型半胱氨酸水平的横断面研究 并且没有骨质疏松症，最终在干预试验中 哪些饮食策略用于降低同型半胱氨酸水平。