Skeletal bone formation viewed across length scales

Access to tools that can image the complex structure of bone on the micrometre to nanometre length scales opens new possibilities. An international research team used NanoMAX to study mineralisation of skeletal bones. The study shows the importance of zinc for the process.

The template for a skeleton is laid out in the embryo by the formation of cartilage and connective tissue. The template then begins to mineralise and grow into bone. In the present study, the researchers used several different methods to study the morphology, composition and structure of bone during formation at a smaller length scale than what has been done before. They looked at the humerus, the equivalent of the long bone of the upper arm, of mice. One thing that the researchers could follow was the distribution of elements, especially zinc, using X-ray fluorescence.

A concentration of zinc is visible in the growth plate of the mouse humerus long bone

“Bone mineral is mainly composed of calcium and phosphorous. However, our study showed zinc concentrations localized just at the border of new and ongoing mineralisation,” says professor Hanna Isaksson from Lund University. “Zinc plays an important role during bone formation, as it is a common co-factor of several enzymes which catalyse the mineralisation of the matrix.”

Basic science studies like this one are important steps and a resource for other researchers to understand disease and treatment in future studies.

“The study provides insight into how normal long bone mineralisation occurs, primarily at the smallest length scales and building blocks,” explains Isabella Silva-Barreto, PhD student and first author of the study. “The findings are essential as a piece of the puzzle in future studies to understand how diseases or drugs may affect mineral deposition.”

The growth front of the bone is called the growth plate. With the nano focused X-ray at NanoMAX, the distribution of elements could be seen in this part.

“The study characterises bone mineralisation over a range of length scales, with a micrometre to nanometre resolution. NanoMAX provided the highest spatial resolution, which was needed to see the distribution of calcium and zinc in the growth plate. It was essential to discover the spatial distribution of Zn at the mineralisation front,” Isaksson concludes.



Isabella Silva Barreto, Sophie Le Cann, Saima Ahmed, Vivien Sotiriou, Mikael J. Turunen, Ulf Johansson, Angel Rodriguez‐Fernandez, Tilman A. Grünewald, Marianne Liebi, Niamh C. Nowlan, Hanna Isaksson, Multiscale Characterization of Embryonic Long Bone Mineralization in Mice, Adv Sci 2020, published online 24 September, DOI: 10.1002/advs.202002524