November 23, 2022

Combining Bone Proteotype and Multiscale Extracellular Matrix Properties for Improved Clinical Fracture Risk Prediction

1st Call, iDoc

Short Summary

As modern societies age, the increasing number of fractures poses a challenge for health care systems worldwide. Hip fractures are especially deleterious, as they are associated with an increased mortality. Within a collaboration between Empa, University of Bern, and University Hospital Bern, we will translate recent advances in microscale characterization techniques into clinical practice to improve current diagnostic tools with patient-specific information on bone composition, micromechanics, and proteotype. The final goal is to achieve higher accuracy in bone strength and fracture risk prediction of individual patients.

Goals

The study aims at translating recent advances in microscale characterization techniques into clinical practice to improve current diagnostic tools by the knowledge of ECM composition, proteotype, and micromechanical properties of each individual patient biopsy. Using clean room methods and FIB technology on bone for high throughput production of micropillars and automated experimental protocols allows massive parallel scanning. Bone strength of the femoral neck is determined by multiscale experimental and computational approaches for patients who underwent total hip arthroplasty. It will be assessed by data mining approaches if knowledge of proteotype and microscale information combined with clinical data can help to estimate fracture strength at higher accuracy.

Significance

By introducing recent advances in microscale characterization, clean room technology, and proteomics to the field of bone biomechanics, this study will establish new methods for simultaneously assessing proteotype and microscale properties of bone extracellular matrix as a biopsy-based screening method. This knowledge may be used for an improved personalized prediction of bone strength and fracture risk in the future.

Background

As modern societies age, the increasing number of fractures poses a challenge for health care systems worldwide. Hip fractures are especially deleterious, as they lead to a loss of mobility and show an increased mortality. Whole bone strength depends primarily on bone mineral density measured by clinical densitometry, but also on the microscale properties resulting from the complex hierarchical organization and continuous remodeling of the bone extracellular matrix. Especially changes in composition, bone turnover, micromechanical properties of the ECM, and their relationship to clinical fracture risk in the presence of a disease, are not known today.

Publications

Casari D, Kochetkova T, Michler J, Zysset P, Schwiedrzik J, Microtensile Failure Mechanisms in Lamellar Bone: Influence of Fibrillar Orientation, Specimen Size and Hydration. Microtensile failure mechanisms in lamellar bone: Influence of fibrillar orientation, specimen size and hydration. Acta Biomaterialia 2021, 131, 391–402. doi:10.1016/j.actbio.2021.06.032
Kochetkova T, Groetsch A, Indermaur M, Peruzzi C, Remund S, Neuenschwander B, Bellon B, Michler J, Zysset P, Schwiedrzik J, Assessing minipig compact jawbone quality at the microscale. Journal of the Mechanical Behavior of Biomedical Materials 2022,134,105405; doi: 10.1016/j.jmbbm.2022.105405
Kormilina, T.; Englisch, S.; Kochetkova, T.; Drobek, D.; Wirth, J.; Zubiri, B. A.; Schwiedrzik, J.; Spiecker, E. Multi-Modal Characterization of Collagen Fibril Orientation in Human Cortical Bone by a Combination of Quantitative Polarized Raman Spectroscopy, Nanoscale X-Ray Computed Tomography and 360° Electron Tomography. Microscopy and Microanalysis 2021, 27 (S1), 96–101.doi:10.1017/S1431927621000970
Indermaur, D. Casari, T. Kochetkova, C. Peruzzi, E. Zimmermann, F. Rauch, B. Willie, J. Michler, J. Schwiedrzik, P. Zysset, Compressive strength of iliac bone ECM is not reduced in Osteogenesis Imperfecta and increases with mineralization. Journal of Bone and Mineral Research, 36(7), 1364–1375. doi:10.1002/jbmr.4286
Maurya, A. K., Parrilli, A., Kochetkova, T., Schwiedrzik, J., Dommann, A., & Neels, A. Multiscale and multimodal X-ray analysis: Quantifying phase orientation and morphology of mineralized turkey leg tendons. Acta Biomaterialia 2021, 129, 169–177. doi:10.1016/j.actbio.2021.05.022
Kochetkova, C. Peruzzi, O. Braun, J. Overbeck, A.K. Maurya, A. Neels, M. Calame, J. Michler, P. Zysset, J. Schwiedrzik, Combining polarized Raman spectroscopy and micropillar compression to study microscale structure-property relationships in mineralized tissues. Acta Biomater. 2021; doi:10.1016/j.actbio.2020.10.034