February 23, 2023

Improving Individual Fracture Risk Prediction in Osteogenesis Imperfecta: An Integrated Multi-omics, Materials Science, and Computational Modeling Approach

7th Call, iDoc

Short Summary

Osteogenesis imperfecta (OI) is a rare heritable disorder causing low bone mass and reduced bone strength, which leads to an increased fracture risk and bone deformities. Today, the causes for the brittle behavior of OI bone are not understood. Using recent advances in microscale characterization techniques, this study will help to improve current diagnostic tools used in a clinical setting by the knowledge of patient-specific bone geometry, the relationship between the microstructure and mechanical strength at several length scales, as well as genetic and biochemical analysis.

Goals

The proposed interdisciplinary study will bring together materials scientists, biomechanics experts, molecular biologists, and clinicians from five major hospitals in Switzerland. It aims at assessing bone strength by experimental and computational approaches spanning several length scales in OI patients and healthy controls who underwent orthopaedic surgery. Using recent advances in microscale characterization techniques, our goal is to improve current diagnostic tools used in a clinical setting by the knowledge of patient-specific bone geometry, the relationship between the microstructure and mechanical strength at several length scales, as well as genetic and biochemical analysis. It will be investigated if integration of these different measurements can help assess the effect of OI types and treatments on the individual bone quality and fracture risk.

Significance

This study will contribute to a better understanding of the changes in bone quality caused by OI. It aims at identifying clinically available biomarkers as well as image-based analyses that allow for improved diagnostics and patient-specific treatment based on an in-depth understanding of the effects of this severe pathology on bone quality and architecture on fracture risk.

Background

Osteogenesis imperfecta (OI) is a rare heritable disorder causing low bone mass and reduced bone strength, which leads to an increased fracture risk and bone deformities. Today, the causes for the brittle behavior of OI bone are not understood. Whole bone strength depends on bone density, but also on microscale tissue properties. Differences in composition, turnover, tissue properties, and their relationship to clinical fracture risk in the presence of a disease are not known. It is therefore important to understand the properties of bone at different length scales, which together with genetic and biochemical information, may help identifying changes in bone quality influencing fracture risk in OI patients.