LEAD EXPOSURE, GENETICS AND OSTEOPOROSIS EPIDEMIOLOGY

主要目的是研究环境铅的影响 暴露和维生素D受体（VDR）基因的等位基因变体， 中年妇女骨质疏松症的发展。 这项研究将 作为三个主要假设的前瞻性评估进行：（1） 铅暴露与骨矿物质密度（BMD）下降有关 和骨转换增加（由血清骨钙素和尿钙素定义）。 I型胶原蛋白交联N端肽或NTX） 妇女 (2)限制性片段长度多态性 由内切核酸酶Bsml和Taql定义的VDR基因与 骨密度下降，骨转换增加。 (3)铅暴露 改变了VDR基因型对测定 BMD和骨转换。 这项研究旨在利用信息 通过两项正在进行的研究收集：护士健康研究（NHS）， 女性慢性病的纵向调查 注册护士和NIEHS R 01-ES 05257支持的电极导线评价 暴露和认知以及肾功能的影响， 包括NHS参与者的大样本。 作为这一正在进行的 研究中，腰椎和髋关节的BMD的两个措施（测量4 或相隔5年）和有关骨铅水平、血铅 水平，饮食，药物使用，激素使用，生殖史， 将为427名NHS参与者提供骨折和病史。 目前的建议包括对存档的生物样本进行实验室分析， 从这427名妇女中提取样本，用于评估VDR基因型、血清 骨钙素和尿NTX。 初步研究结果包括 发现：（1）骨铅的横截面反向关联 水平与BMD，和（2）两者的横截面正相关 在前302名妇女的子样本中， 研究至今。 这些结果初步支持了 假设骨铅水平增加与 BMD的预期降低和骨转换活性的增加。 BMD 是骨质疏松症和骨质疏松性骨折的关键危险因素， 每年花费180亿美元， 估计终生死亡风险（妇女）和乳腺癌。 评估骨质疏松症的潜在环境危险因素， 证实了最近对这种疾病遗传学的研究结果， 以及对可能的基因环境的理解 与这种疾病的发展有关的相互作用是非常重要的 公共卫生的重要性作为一种手段， 骨质疏松症的治疗和预防策略。

The primary objective is to study the effects of environmental lead exposures and allelic variants of the vitamin D receptor (VDR) gene on the development of osteoporosis in middle-aged women. The study will be conducted as a prospective evaluation of three major hypotheses: (1) Lead exposure is associated with declines in bone mineral density (BMD) and increases in bone turnover (defined by serum osteocalcin and urinary cross-linked N telopeptide of type I collagen or NTX) in middle-aged women. (2) Specific restriction fragment length polymorphisms within the VDR gene defined by the endonucleases Bsml and Taql are associated with declines in BMD and increases in bone turnover. (3) Lead exposure modifies the effects of VDR genotype on the determination of changes in both BMD and bone turnover. The study is designed to use information collected through two ongoing studies: the Nurses' Health Study(NHS), an established longitudinal investigation of chronic disease in female registered nurses, and an NIEHS R01-ES05257 supported evaluation of lead exposure and cognitive and renal function in middle-aged adults that includes large sample of NHS participants. As part of this ongoing research, two measures of BMD at the lumbar spine and hip (measured 4 or 5 years apart) and information regarding bone lead levels, blood lead levels, diet , medication use, hormone use, reproductive history, fracture and medical history will be available for 427 NHS participants. The current proposal includes laboratory analyses of archived biological specimens from these 427 women for assessment of VDR genotype, serum osteocalcin, and urine NTX. Results of preliminary studies include findings of: (1) cross-sectional inverse associations of bone lead levels with BMD, and (2) cross-sectional positive associations of both blood and bone lead with urine NTX in a subsample of the first 302 women studied to date. These results provide initial support for the hypothesis that increased bone lead levels are associated with prospective decreases in BMD and increased bone turnover activity. BMD is a critical risk factor for osteoporosis and osteoporotic fractures, which are associated with annual cost of 18 billion and pose the same estimated lifetime risk of death (in women) as does breast cancer. Evaluating potential environmental risk factors for osteoporosis, corroborating results of recent studies of the genetics of this disease, and achieving and understanding of possible gene-environment interactions related to the development of this disorder are of great public health importance as a means for identifying appropriate strategies for osteoporosis treatment and prevention.