Utilizing Saliva to Measure Bone Turnover

描述(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。由于许多骨质疏松症患者都是老年人，衡量保留骨骼疗法的成功不仅需要敏感的测试，还需要方便的患者程序。在目前的研究中，我们建议测试唾液(一种容易收集的生物液体)在一组围绝经期妇女中测量骨转换变化的效用，这些妇女参加了一项为期5年的随机、双盲、安慰剂对照研究，该研究是Kronos早期雌激素预防研究(Keep)的一部分。梅奥诊所是 全国8个参赛中心。Keep的主要目的是研究雌激素的作用。 关于动脉粥样硬化的配方。幸运的是，还将获得血清中的骨转换标记水平和骨密度值，这意味着Keep为研究唾液提供了一个非同寻常的机会。这一应用的中心假设是，存在于人类唾液中的宿主来源的骨特定蛋白将作为全身骨转换和骨密度的生物标记物。我们建议的理由是，如果唾液中的骨转换标志物水平与血清和/或骨密度水平相关，那么唾液，一种容易收集的生物液体，可以用来监测全身骨转换。我们为开展这项研究做好了特别充分的准备，因为：(1)我们已经证明，可以通过传统的酶联免疫分析方法在人类唾液中检测到骨转换标志物；(2)Keep基础设施确保了严格的临床研究环境。我们将通过以下方式测试我们的假设： 以下是两个具体目标： 1)在受控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记物水平代表了血清中相同生物标记物的水平。 2)在对照临床试验人群中，确定唾液骨转换标志物水平的变化与骨密度变化之间的关系。工作假设是，与接受安慰剂治疗的受试者相比，接受MHT治疗的受试者的唾液生物标记物水平的变化衡量的骨转换与BMD的增加有关。 这项辅助研究申请涉及NIDCR口腔、牙科和颅面部疾病基因组学和蛋白质组学小组概述的一项关键指令，该指令强调需要将唾液作为诊断工具进行调查。我们预计，我们的结果将确定唾液生物标志物如何用于评估骨质疏松症患者或有骨质疏松风险的患者的骨状态。

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.