Fracture Risk Prediction in Children and Adults with Osteogenesis Imperfecta (OI)
Osteogenesis imperfecta (OI) is an inherited disease of collagen synthesis which causes skeletal deformity and bone fragility. It is characterized by a broad variability among affected individuals that can include frequent fractures of the lower extremities. Treatment includes fracture prevention/management as a central focus with goals of maintaining ambulatory and functional abilities and quality of life. Current literature postulates that a deficient collagen network and abnormal mineralization are responsible for the mechanical properties of OI bone tissue. An accurate biomechanical model of the lower extremities is proposed in this work to better understand and predict and ultimately rehabilitate and better control fracture occurrence. In addition to an array of clinical assessment tools, state of the art technologies including nanoindentation, 3-D gait analysis and finite element analysis will be employed to develop the proposed model. A primary design goal includes model flexibility for more universal yet specific application in children and young adults with OI. Testing and evaluation is proposed for a group of twenty-four (24) patients with OI who will be followed at six-month intervals over the course of the study.
This work will use the novel technology of nanoindentation to better characterize the structural properties of OI bone in children and young adults. For this parallel portion of the work bone samples will be gathered during routine repairative surgery from thirty-four individuals (children and young adults) with OI who have experienced fractures. The bone will then be analyzed to determine strength, stiffness, modulus, and brittleness/ductility at the trabecular level. Results will be compared to current published studies and used to significantly enhance the existing data.
A hallmark of this proposal is the construction of a finite element model of the lower extremities. In addition to published material property data, input for the model will come from 3-D quantitative gait studies (for constraints and boundary conditions) and our parallel nanoindentation studies (for material property data). The resulting model will accurately reflect the structural anatomy, mechanical properties and loads on the long bones of the lower extremities. The model will be flexible and specifically fit to the study participants’ bony geometry on the basis of radiographs. Validation and refinement of the model will occur as twenty-four (24) ambulatory subjects with OI are evaluated and followed during four successive clinical visits (six month intervals). During the course of the study, the model boundary conditions will be altered to explore the influence of factors such as bone size, geometry (bowing), bone structure and functional loading on the development of fractures. A comparison of model parameters to clinical assessment results will provide critical insight with regard to fracture development, therapeutic intervention and longer-term outcomes.
The synthesis of published material property data, unique mechanical test data on the nano scale, quantitative gait analysis and finite element modeling should provide a higher level of sophistication in our understanding of bone biology and mechanical behavior in OI. Validation with our study population of children and young adults with OI will allow further refinement as the model is applied. Ultimately we hope to offer an improved approach to fracture risk prediciton in children and young adults by combining information from quantitative models and an array of clinical instruments.
U. S. Department of Education, National Institute on Disability and Rehabilitation Research (NIDRR)
H133G050201
Principal Investigator: Gerald F. Harris, Ph.D., P.E.
11/1/05 – 10/31/10
Click here for a list of publications related to this grant.