Salivary Biomarkers to Predict Alveolar Bone Loss

描述：本R21应用程序的目标是开发一个客观，快速的系统，可以轻松地在牙科中使用！办公室确定未来牙槽骨丢失的高风险患者。这些信息将使医生能够针对最需要治疗的患者采取适当的干预措施，并避免对这些服务需求有限的患者进行昂贵和耗时的治疗。我们将利用一种既定的方法，使用包裹有特异性抗体的顺磁微球，一步捕获、检索、浓缩和识别与唾液中牙周骨破坏相关的生物标志物。本研究的一般假设是，宿主来源的骨吸收因子，如人类唾液中的白细胞介素-1- β (il -1- β)、肿瘤坏死因子- α (TNFalpha)、白细胞介素-6 （il -6）和前列腺素- e2 (PGE2)，将作为主动骨破坏的生物标志物。此外，我们还将使用该技术浓缩骨破坏产物，如I型胶原蛋白（ICTP）的c -末端肽吡啶啉交联、骨钙素和骨连接素。然后用简单的比色法对这些浓缩产品进行定量。这些生物标志物，所有这些生物标志物之前都被报道在活动性牙周病患者的龈沟液（GCF）中升高，与其他已知的危险因素（如年龄、吸烟等）一起，将用于开发统计诊断模型，用于预测未来的牙槽骨丢失，纵向监测患者的任何PD状态变化，并评估治疗成功或失败。

DESCRIPTION: The goal of this R21 application is to develop an objective, rapid system that can be used with ease in the dental! office to identify patients at high risk for future alveolar bone loss. This information will allow the practitioner to target appropriate interventions to patients in most need of treatment and avoid expensive and time consuming treatment for patients having limited need for these services. We will exploit an established method that uses paramagnetic microspheres coated with specific antibodies to capture, retrieve, concentrate and identify biomarkers associated with periodontal bone destruction in saliva in one step. The general hypothesis of this study is that host-derived bone resorptive factors such as interleukin-1-beta(IL-1-beta, tumor necrosis factor-alpha(TNFalpha, interleukin-6 (ll-6), and prostaglandin-E2 (PGE2) from human saliva will serve as biomarkers of active bone destruction. Additionally, we will use this technology to also concentrate products of bone destruction, such as C-telopeptide pyridinoline crosslinks of Type I collagen (ICTP), osteocalcin and osteonectin from human saliva. These concentrated products will then be quantitated using simple colorometric methods. These biomarkers, all of which have been previously reported to be elevated in gingival crevicular fluid (GCF) of subjects with active periodontal disease, in conjunction with other well known risk factors, e.g. age, tobacco use, etc., will be used to develop statistical diagnostic models for predicting future alveolar bone loss, monitoring patients longitudinally with respect to any PD status change and evaluating treatment success or failure. The use of the magnetic microspheres to quantitate biomarkers in saliva has several advantages. The microspheres allow concentration of small amounts of biomarkers that may be present in saliva. The microspheres can also be coated with antibodies with multiple specificities that will allow simultaneous quantitation of multiple target biomarkers from the same saliva sample. Saliva, unlike GCF, is readily accessible and can be rapidly collected with minimal effort. We envision that this approach could be conveniently adapted in the future for use by practicing dentists to provide objective information to assess risk for periodontal bone loss.