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，从受影响的男女人数和不断攀升的病人护理费用来看，这种令人衰弱的疾病的发生率将显著增加。最近的研究表明，骨质疏松症的发生有很强的遗传因素。研究还表明，骨质疏松症是一种复杂的疾病，有几个基因相互作用，为随着年龄的增长和某些较年轻的人的骨质流失奠定基础。宾夕法尼亚州兰开斯特县的老阿米什人是一个同质的群体，是通过候选基因分析和位置克隆方法识别骨质疏松症易感基因的理想群体。骨质疏松症先证者可以通过脊椎或髋部骨折病史和骨矿密度(BMD)测量来确定。此外，还对血清I型前胶原羧基末端肽(PICP)、骨钙素、25羟基维生素D和尿标记物脱氧吡啶(DPD)进行了分析。在本报告所述期间，对135名参与者的骨密度测量以及血清和尿骨代谢标志物等数据进行了统计分析，以寻找可能的相关性。定义的骨质疏松症人群在BMD、DPD和PICP值方面与正常队列相比显示出差异。血清标记物(骨钙素和25羟基维生素D)在骨质疏松症患者和正常患者之间没有显著差异。在两组之间，没有显著的年龄或性别差异。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丢失率(以BMD和DPD衡量)，以及不同的诊断年龄。随着两个研究群体的表型定义，现在为候选基因多态的初步筛选做好了准备。要研究的基因多态性包括维生素D受体、雌激素受体α和β以及I型胶原的基因。仅限核心实验室；没有住院日或门诊就诊。

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.