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，无论是受影响的妇女和男子的人数，还是病人护理费用的不断上升。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。这些研究还表明，骨质疏松症是一种复杂的疾病，随着年龄的增长和某些年轻人，几个基因相互作用为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的群体，是通过候选基因分析和定位克隆方法鉴定骨质疏松症易感基因的理想人群。骨质疏松症先证者通过脊椎或髋部骨折史和骨矿物质密度（BMD）测量确定。此外，还分析了血清标志物I型前胶原羧基末端肽（PICP）、骨钙素、25羟基维生素D和尿液标志物脱氧吡啶酚（DPD）。在本报告期间，对135名参与者的数据（包括BMD测量和血清及尿液骨代谢标志物）进行了统计学分析，以确定可能的相关性。与正常人群相比，定义的骨质疏松人群在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，没有平均值之间的差异，骨质疏松症和正常参与者。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）和不同的诊断年龄。随着两个研究人群的表型定义，现在的阶段是候选基因多态性的初步筛选。待研究的多态性包括维生素D受体、雌激素受体α和β以及I型胶原蛋白的多态性。仅限核心实验室;无住院日或门诊访视。

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.