GENETICS OF OSTEOPOROSIS IN OLD ORDER AMISH

骨质疏松症是发达国家的一个主要公共卫生问题。据估计，到2050年，这种使人衰弱的疾病的发病率将显著增加，无论是在受影响的男女人数方面，还是在病人护理费用不断上升方面。最近的研究表明，在骨质疏松症的发展中有很强的遗传成分。研究还表明，骨质疏松症是一种复杂的疾病，几个基因相互作用，为老年和某些年轻人的骨质流失奠定了基础。宾夕法尼亚州兰开斯特县的旧秩序阿米什人是一个同质人群，通过候选基因分析和定位克隆方法，是鉴定骨质疏松易感基因的理想选择。骨质疏松先证者通过椎体或髋部骨折史和骨密度（BMD）测量来确定。此外，还分析了血清标志物前胶原I型羧基末端肽（PICP）、骨钙素、25羟基维生素D和尿标志物脱氧吡啶啉（DPD）。在本报告期内，对135名参与者的骨密度测量、血清和尿骨代谢指标进行了可能的相关性统计分析。与正常人群相比，骨质疏松人群在BMD、DPD和PICP值方面表现出差异。血清标志物（骨钙素和25羟基维生素D）显示骨质疏松症和正常参与者之间没有平均差异。在两组之间，没有明显的年龄或性别差异。然而，在骨质疏松组中，年龄和性别差异很明显，男性和女性表现出不同的骨质流失率（通过BMD和DPD测量），以及不同的诊断年龄。随着这两个研究群体的表型定义，现在开始对候选基因多态性进行初步筛选。待研究的多态性包括维生素D受体、雌激素受体以及I型胶原蛋白的多态性。仅限核心实验室；没有住院日或门诊。

Osteoporosis is a major public health problem in developed countries. By the year 2050, it is estimated that the incidence of this debilitating disorder will significantly increase both in terms of the numbers of women and men affected and in the escalating cost of patient care. Recent studies indicate that there is a strong genetic component in the development of osteoporosis. The studies also indicate that osteoporosis is a complex disorder with several genes interacting to set the stage for bone loss with advancing age and in certain younger individuals. The Old Order Amish of Lancaster County, Pennsylvania, are a homogeneous population that is ideal for the identification of osteoporosis susceptibility genes by candidate gene analysis and positional cloning methodology. Osteoporotic probands have been identified by history of vertebral or hip fracture and by bone mineral density (BMD) measurements. In addition, the serum markers procollagen type I carboxyl terminal peptide (PICP), osteocalcin, 25 hydroxy vitamin D, and the urinary marker deoxypyridinoline (DPD), have been analyzed. During the current reporting period, the data including BMD measurements and serum and urinary bone metabolism markers have been statistically analyzed for possible correlations for 135 participants. The defined osteoporotic population exhibited differences compared to normal cohorts in terms of BMD, DPD and PICP values. The serum markers (osteocalcin and 25 hydroxy vitamin D) showed no mean differences between osteoporotic and normal participants. Between the two groups, there were no significant age or gender differences. Within the osteoporotic group, however, age and gender differences were apparent with men and women exhibiting differing rates of bone loss (as measured by BMD and DPD), and differing ages of diagnosis. With the two study populations phenotypically defined, the stage is now set for an initial screening of candidate gene polymorphisms. The polymorphisms to be studied include those of the vitamin D receptor, estrogen receptor alpha and beta, as well as, type I collagen. CORE LABORATORY ONLY; NO INPATIENT DAYS OR OUTPATIENT VISITS.