Bone is a dynamic tissue that naturally and continually undergoes turnover with new bone formation by osteoblasts and old bone resorption by osteoclasts at a balanced rate;any imbalance between the two rates results in varying states of abnormal bone turnover such as osteoporosis, with accompanying bone fragility and increased risk of fracture. Although osteoporosis is a common condition, particularly in older women, it is usually only diagnosed at a later stage when morbid symptoms, such as spine or hip fractures, have occurred. Currently, the most reliable methods for bone mineral density (BMD) measurements are imaging techniques such as dual photon absorptiometry (DPA), quantitative computed tomography (QCT), and dual energy X-ray absorptiometry (DEXA). Although these diagnostic techniques are accurate, they are not optimal for routine screening of bone density because they are expensive, relatively time- and labor-intensive compared to point- of-care tests, and often unavailable to for routine screening of the large population at risk for osteoporosis. Current laboratory-based tests such as enzyme linked immunoassay (ELISA) kits for the detection of individual biomarkers in either blood or urine are generally not offered for screening and treatment follow-up applications because they are invasive and expensive. Reliable measurements of bone turnover markers have been studied to evaluate their role in the diagnosis and prediction of bone deterioration;these studies assessed their correlation to BMD measurements, presented in T-score values, with great agreement. Bone turnover markers can be assayed from blood or urine, however, recent attention has focused on salivary diagnostics because of their convenient and non-invasive nature of sampling. Intelligent Optical Systems (IOS) proposes to develop a cost-effective, easy-to-use, non-invasive screening platform for bone turnover salivary markers based on a lateral flow test strip (LFTS) technique previously developed by IOS. This platform will assess two key bone activities: bone formation, presented in osteocalcin (OC), and bone resorption, presented in collagen crosslink deoxypyridinoline (D-PYR). Highly stable quantum dot labeling techniques will provide detection via fluorescence measurements, and will allow multiplexed detection using the same sample, test strip, and excitation light source. Phase I will focus on demonstrating the feasibility of achieving reproducible, sensitive measurements of OC and PYR/D-PYR levels in buffer and modeled saliva. In collaboration with Prof. Roger B. Johnson of the University of Mississippi Medical Center, Department of Periodontics and Preventive Sciences, a simple prospective study will include human saliva sample testing in comparison with urine/blood levels and BMD measurements. Phase II will demonstrate LFTS sensitivity and reliability in a large population study using salivary samples to validate detection accuracy and meet clinical requirements.

Public Health Relevance

Intelligent Optical Systems proposes to develop a new technique for a non-invasive salivary-based bone-loss marker detection platform. The detector is designed to have the measurement accuracy required for screening applications without the need for blood or urine sampling and testing, and will therefore contribute to a quick diagnosis and appropriate treatment. The proposed detection platform will enable routine screening of bone loss biomarkers via an inexpensive, non-invasive method that can be employed in point-of-care (POC) testing. Routine screening will result in an earlier detection of bone loss, which in turn will result in more effective treatment options, improving the quality of life of osteoporotic patients. Significant cost savings will be realized in the reduction of osteoporosis-related fractures and associated treatment.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Musculoskeletal Tissue Engineering Study Section (MTE)
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Denucci, D J
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Intelligent Optical Systems, Inc.
United States
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