About Markus A. Hartmann

Markus Hartmann studied physics at the University of Vienna. He obtained his PhD under the supervision of Peter Fratzl at the Max-Planck-Institute of Colloids and Interfaces in Potsdam/Germany, where he was studying stochastic models to simulate bone remodeling. After several postdoctoral positions in Germany, France and Austria, he joined the Ludwig Boltzmann Institute of Osteology in Vienna in 2018, where he is heading the Mineral, Structure and Function group. His research interests lie in the investigation of the structure of bone of healthy individuals and the change of this structure during ageing and in (rare) diseases. Special emphasis is put on the mineralization of the bone material and its mechanical behavior. A combination of various methods from different scientific disciplines, like physics, materials science, chemistry or biology allow for a better understanding of the different aspects of bone - from the material to the endocrine organ.

About the seminar

Bone is a complex hierarchical structure, on the lowest level consisting of an organic collagen matrix that is reinforced by mineral particles. I will discuss several methods that allow to analyze bone structure in a spatially resolved manner. I will show how these methods can be used to assess bone structural changes with age as well as differences between normal and pathological bone due to (rare) diseases. Micro-CT methods allow to investigate how trabecular architecture and cortical porosity change with age. In aged individuals trabecular bone volume, trabecular thickness and number are decreasing, while cortical porosity is increasing. I will explain how local mineralization with a a spatial resolution of approx. 1 micrometer can be assessed using quantitative backscattered electron imaging [1]. In combination with tetracycline labeling it will be shown that it is not only possible to measure the current mineralization, but also to estimate the mineralization kinetics. Mineralization kinetics are accelerated in patients suffering from osteogenesis imperfecta compared to healthy individuals [2]. Furthermore, it will be shown how the images obtained for mineralization assessment can also be used to characterize osteocyte characteristics. These measurements show that osteocyte density is decreasing with age and is higher in the cortex compared to the spongiosa [3]. Changes in bone structure between treated and treatment na¨ıve bone samples can be assessed. One example that I will present, is the influence of Burosumab, a fully human monoclonal FGF23 antibody that is approved for treatment of x-linked hypophospatemia in adults [4]. Changes in the lacuno-canalicular network can be obtained in full 3D by measuring the fluorescent signal in rhodamine stained samples using laser scanning confocal microscopy, highlighting changes between wildtype and knock-out mice in an animal model for osteogenesis imperfecta [5]. Finally, I will also discuss how local mechanical properties can be obtained using scanning acoustic microscopy [6].

^{The OLCN of a human osteon, imaged with confocal microscopy of a rhodamine stained sample.} 

References

[1] M. A. Hartmann et al., “Quantitative backscattered electron imaging of bone using a thermionic or a field emission electron source”, Calcified Tissue International 109, 190 (2021).

[2] B. M. Misof et al., “Accelerated mineralization kinetics in children with osteogenesis imperfecta type 1”, Bone 166, 116580 (2023).

[3] S. Blouin et al., “Osteocyte lacunae in transiliac bone biopsy samples across life span”, Acta Biomaterialia, 10.1016/ j.actbio.2022.11.051 (2023).

[4] N. Fratzl-Zelman et al., “Bone matrix mineralization and response to burosumab in adult patients with x-linked hypophosphatemia: results from the phase 3, single-arm international trial”, Journal of Bone and Mineral Research 37, 1665–1678 (2022). 

[5] G. Hedjazi et al., “Alterations of bone material properties in growing ifitm5/bril p.s42 knock-in mice, a new model for atypical type vi osteogenesis imperfecta”, Bone 162, 116451 (2022). 

[6] S. Blouin et al., “Cortical bone properties in the brtl/+ mouse model of osteogenesis imperfecta as evidenced by acoustic transmission microscopy”, Journal of the Mechanical Behavior of Biomedical Materials 90, 125–132 (2019).