Utilizing Saliva to Measure Bone Turnover

描述（由申请人提供）：骨质疏松症影响超过4400万美国人，导致每年直接支出超过200亿美元。衡量骨保留疗法的成功不仅需要敏感的测试，而且还需要方便的患者程序，因为许多骨质疏松症患者是老年人。在本研究中，我们建议测试唾液（一种易于收集的生物流体）的效用，以测量一组围绝经期妇女的骨转换变化，这些妇女参加了一项随机、双盲、安慰剂对照的5年研究，该研究是Kronos早期雌激素预防研究（KEEPS）的一部分。马约诊所是 全国共有8家参展企业。KEEPS的主要目的是研究雌激素的作用 制剂对动脉粥样硬化的影响。幸运的是，还将获得血清中的骨转换标志物水平和骨矿物质密度值，这意味着KEEPS提供了一个研究唾液的绝佳机会。本申请的中心假设是存在于人唾液中的宿主来源的骨特异性蛋白质将用作全身性骨转换和骨矿物质密度的生物标志物。我们提出的基本原理是，如果唾液中骨转换标志物的水平与血清和/或BMD的水平相关，那么唾液，一种容易收集的生物流体，可以用于监测全身骨转换。我们为开展这项研究做了特别充分的准备，因为：（1）我们已经证明，骨转换标志物可以通过人类唾液中的传统酶联免疫测定法检测到;（2）KEEPS基础设施确保了严格的临床研究环境。我们将通过追踪 以下两个具体目标： 1)在对照临床试验人群中确定唾液骨转换标志物水平是否与血清水平相关。工作假设是唾液中的生物标志物水平代表血清中相同生物标志物的水平。 2)确定对照临床试验人群中唾液骨转换标志物水平变化与BMD变化之间的关系。工作假设是，与接受安慰剂治疗的受试者相比，通过接受MHT的受试者唾液中唾液生物标志物水平的变化测量的骨转换与BMD增加相关。 这项辅助研究申请解决了NIDCR口腔、牙齿和颅面疾病基因组学和蛋白质组学小组概述的一项关键指令，该指令强调需要研究唾液作为诊断工具。我们预计，我们的研究结果将确定如何唾液生物标志物可用于评估骨质疏松症患者的骨状态，或在风险，骨质疏松症。

DESCRIPTION (provided by applicant): Osteoporosis affects over 44 million Americans leading to direct annual expenditures in excess of $20 billion. Measuring the success of bone-sparing therapies requires not only sensitive tests but also convenient patient procedures since many osteoporosis sufferers are elderly. In the present study, we propose to test the utility of saliva, an easily collected biofluid, to measure changes in bone turnover in a group of peri-menopausal women who are participating in a randomized, double-blind, placebo-controlled 5-year study conducted as part of the Kronos Early Estrogen Prevention Study (KEEPS). Mayo Clinic is one of 8 participating centers nationally. The primary purpose of KEEPS is to study the effect of estrogen formulations on atherosclerosis. Fortuitously, bone turnover marker levels in serum and bone mineral density values will also be obtained meaning that KEEPS offers an extraordinary opportunity to investigate saliva. The central hypothesis of this application is that host derived bone-specific proteins present in human saliva will serve as biomarkers of systemic bone turnover and bone mineral density. The rationale for our proposal is that if levels of bone turnover markers in saliva correlate with levels in serum and/or BMD, then saliva, an easily collected biofluid, can be used to monitor systemic bone turnover. We are particularly well prepared to undertake this research because: (1) we have demonstrated that the bone turnover markers can be detected by conventional enzyme-linked immunoassays in human saliva; and (2) the KEEPS infrastructure ensures a rigorous clinical research environment. We will test our hypothesis by pursuing the following two specific aims: 1) Determine whether salivary bone turnover marker levels correlate with serum levels in a controlled clinical trial population. The working hypothesis is that levels of biomarkers in saliva are representative of levels of the same biomarkers in serum. 2) Determine the relationship between changes in salivary bone turnover marker levels and changes in BMD in a controlled clinical trial population. The working hypothesis is that bone turnover as measured by changes in levels of salivary biomarkers in the saliva of subjects receiving MHT is associated with increase in BMD when compared to subjects receiving placebo therapy. This ancillary study application addresses a key directive outlined by the NIDCR Panel on Genomics and Proteomics of Oral, Dental and Craniofacial Diseases which stressed the need to investigate saliva as a diagnostic tool. We anticipate that our results will identify how salivary biomarkers can be used to assess the osseo-status of patients with, or at risk for, osteoporosis.