Salivary-Based Bone-Loss Marker Detection Platform for Point-of-Care Screening

描述（由申请人提供）：骨是一种动态组织，不断经历新骨形成（通过成骨细胞）和旧骨吸收（通过破骨细胞）;它们的速率在所有生命阶段都处于平衡状态，但随着年龄的增长，骨密度逐渐丧失。在某些人群中，发生骨丢失的异常平衡（骨质疏松症），年龄> 50岁的白色女性中髋关节、脊柱或前臂骨折的终生风险为40%，白色男性中为13%。[1，2]骨质疏松症是一种全身性疾病和"无声流行病"，通常在晚期诊断，经常在骨折后。与骨质疏松症相关的骨矿物质密度（BMD）损失可以通过双光子吸收测定法（DPA）、定量计算机断层扫描（QCT）或双能X线吸收测定法（DEXA）可靠地测量。[1，2，3，4]虽然这些诊断方法可以准确测量BMD，但与即时检测相比，它们昂贵且耗时耗力;此外，硬件不适合小型化。同样，由于时间和成本原因，通常通过酶联免疫测定（ELISA）实验室检测评估的血清或尿液中排泄的生物标志物不用于常规筛查和治疗随访。为了解决这些局限性，并且作为诊断骨转换的简单、无创、易于使用、具有成本效益的常规手段，智能光学系统（IOS）正在开发一种基于IOS先前开发的用于监测骨转换的唾液标志物的简单侧流测定（LFTA）技术的平台。这将使临床医生能够在床旁（POC）环境中进行骨质疏松症的常规非侵入性筛查。简单的LFA平台，固定有对多种骨丢失唾液生物标志物敏感的特异性试剂，设计用于临床相关检测限小于10分钟，具有非侵入性、可靠筛查所需的灵敏度和特异性水平。验证研究的金标准将是使用已知羟基磷灰石量的体模通过腰椎（L1-L2）的QCT成像分析测量的绝对和相对BMD。[2，3，4] I期研究工作建立了唾液骨丢失标志物（OC和DPD）的测定平台。该检测试剂盒显示出与临床要求相关的灵敏度，显示出与患者诊断的高度相关性。[5，6]一项前瞻性临床研究证实了OC与骨矿物质密度（BMD）以及唾液和血液样本的金标准ELISA生物标志物测量试剂盒的良好相关性。在第二阶段，我们将扩大已建立的标志物检测的临床试验，包括一项广泛的人类前瞻性研究，以确定统计可靠性和种族的影响， 年龄和饮食在更大的人群中。

DESCRIPTION (provided by applicant): Bone is a dynamic tissue that continually undergoes new bone formation (by osteoblasts) and old bone resorption (by osteoclasts); their rates are in balance throughout all life stages, but a gradual loss of bone density occurs with aging. In some people, an abnormal balance of bone loss occurs (osteoporosis), with a lifetime risk of fracture of the hip, spine, or forearm of 40% in white women and 13% in white men age >50 years.[1,2] Osteoporosis is a systemic disease and "silent epidemic" that is usually diagnosed at a late stage, frequently after a fracture. Bone mineral density (BMD) loss associated with osteoporosis can be measured reliably by dual photon absorptiometry (DPA), quantitative computed tomography (QCT), or dual energy X-ray absorptiometry (DEXA).[1,2,3,4] Although these diagnostic methods measure BMD accurately, they are expensive and time- and energy-intensive compared to point-of-care tests; moreover, the hardware is not amenable to miniaturization. Similarly, biomarkers excreted in serum or urine, usually assessed by enzyme linked immunoassay (ELISA) laboratory testing, are not offered for routine screening and treatment follow-up for time and cost reasons. To address these limitations, and as a simple, noninvasive, easy-to-use, cost- effective, and routine means of diagnosing bone turnover, Intelligent Optical Systems (IOS) is developing a platform based on a simple lateral flow assay (LFTA) technique developed previously by IOS for monitoring salivary markers of bone turnover. This will enable clinicians to perform routine noninvasive screening for osteoporosis in a point-of-care (POC) setting. The simple LFA platform, immobilized with specific reagents sensitive to multiple bone loss salivary biomarkers, is designed to target clinically relevant detection limits n less than 10 min., with the required level of sensitivity and specificity for non-invasive, reliabl screening. The gold standard for validating the study will be absolute and relative BMD as measured by QCT imaging analysis of the lumbar spine (L1-L2) using a phantom with known quantities of hydroxyapatite.[2,3,4] The Phase I research effort established assay platforms for salivary bone loss markers (OC and DPD). The assays exhibited sensitivity that is relevant to clinical requirements, showing a high degree of correlation with patient diagnosis.[5,6] A prospective clinical study confirmed excellent correlation of OC with both bone mineral density (BMD) and the gold standard ELISA biomarker measurement kits for saliva and blood samples. In Phase II we will expand the clinical testing of the established marker detection to include an extensive human prospective study to determine the statistical reliability and the effects of race, age, and diet in a larger population.