Salivary Biomarkers to Predict Alveolar Bone Loss

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.