Characterization of the Biomineralization Process to Develop Bone Quality

Investigators: Yong Wang, Jeff Gorski, Lynda Bonewald, J David Eick, UMKC-Dentistry (Co-PIs)
Pathological mineralization or an imbalance in lamellar and woven bone formation can lead to bone disease such as osteomalacia, rickets, osteoporosis, osteogenesis imperfecta, and others. Using state of the art bioengineering approaches to characterize normal and abnormal woven and lamellar bone should lead to potential means to diagnose bone disease and predisposition to fracture in order to intervene with preventative and therapeutic treatment. The proposed work includes: identify and characterize processes responsible for biomineralization in woven or primary bone, identify and characterize processes whereby osteoid osteocytes control and initiate mineralization of lamellar bone, integrate the characteristics of normal and abnormal woven and lamellar bone using state of the art biophysical and bioinformatics approaches in order to generate a bone tissue profile that defines bone quality. Bone mineral density is the gold standard for predicting bone fragility, however, in many cases, individuals with similar densities will have dramatically different susceptibility to fracture. Despite bone mineral density's contribution to fracture, other less clear properties of the skeleton contribute to bone quality, an independent risk factor for fracture. We propose a new approach of "bone tissue profiling" that will lead to identification of those parameters which could lead to better prediction, prevention and treatment of bone disease. Comparison of these profiles should lead to the identification of novel biomarkers, understanding of molecular mechanisms responsible for generation and maintenance of bone quality, and identification of specific targets for further studies aimed at improving bone quality and strength leading to improved health.