Osteogenesis imperfecta (OI or brittle bone disease) is a major genetic disorder of bone characterized by multiple spontaneous fractures, skeletal deformities and severe disabilities. These disabilities include reduced mobility, hearing loss, and respiratory problems. There is currently no cure for OI, and treatments relying on the use of bisphosphonates have questionable efficacy. With improved management, these children now progress to adulthood, where the challenge of age-related fractures occurs. There is therefore a critical need for fundamental, quantitative research into bone that can then support the development of new, effective treatments. More effective treatments will enhance the quality of life of people with OI. As fracture and fragility are the main symptoms of OI, this CAREER proposal aims to first understand what features of OI bone make it more susceptible to fracture and then evaluate the efficacy of current therapies. This will be done by examining the actual bone resistance to fracture. Combining rigorous fracture mechanics experiments with high-resolution imaging and innovative computational models, this project will examine the relation between structure, composition, and mechanics of the bone in OI with and without treatment. This will then reveal the mechanisms of crack propagation in OI bone at an unprecedented detail. It will also provide a foundation for the development of improved therapies that target the key properties in bone that will affect bone fragility. The techniques developed through this project can be applied to any bone fragility disease, which will further advance the development of effective therapies for these conditions. Improved outcomes for individuals with these disorders has the potential for substantial economic, health and welfare benefits to society. The educational plan of this CAREER plan promotes training, mentoring and learning of diverse students, representing the next-generation of engineers. By broad outreach activities connected with research, we will inspire and attract children, students at any age and the general public to STEM disciplines. These include social media videos about bone mechanics, learning modules for K12 students, and inviting young adults with OI to participate in workshops to learn about the latest research and bone mechanics in general.
Osteogenesis imperfecta (OI) is a genetic disorder that causes an extreme susceptibility to spontaneous fracture which then progresses such that skeletal deformities and severe disabilities result. Current treatments involve the use of bisphosphonates; however, their efficacy has not yet been demonstrated. By combining cutting edge experimental techniques for the analysis of fracture mechanics with high resolution imaging and novel finite element models, this project will investigate the relationship between structure, composition, and mechanics in OI bone with and without treatment. Improved understanding of the fracture mechanisms associated with OI and the factors that cause the fracture susceptibility will support the development of improved therapies that can then target those aspects of bone structure and molecular organization. The educational component of this project seeks to increase understanding of bone mechanics and its importance, both among engineering students and the public. A combination of formal and informal educational activities will reach undergraduate and graduate engineering students, K12 students, and the general public. Activities are also included to encourage underrepresented groups, especially women and individuals with disabilities, to pursue STEM education and careers.
