Bone properties in osteogenesis imperfecta: what can we learn from a bone biopsy beyond histology?

Knocheneigenschaften bei Osteogenesis imperfecta: Was können wir jenseits der Histologie aus einer Knochenbiopsie lernen?

Summary

Transiliac bone biopsy samples are used to evaluate histology and bone cell activity in unclear pathological conditions. However, much additional information can be obtained from such bone samples. Using the example of osteogenesis imperfecta (OI), the current article describes how biopsy samples can be further used to study bone material characteristics including the degree of matrix mineralization, organic matrix properties, mineral particle size and bone nanoporosity. OI is a heritable collagen-related disorder that is phenotypically and genetically extremely heterogeneous. One essential finding was that OI bone is hypermineralized independently of clinical severity. Moreover, mineral particles in OI bone are of normal size or even smaller, but more densely packed than normally. Another recent finding was that in some forms of OI, collagen orientation is highly disorganized, indicating that the collagen–mineral particle network is profoundly altered in OI. These findings have contributed to the understanding of impaired bone strength in OI.

Zusammenfassung

Transiliakale Beckenkammbiopsien werden bei unklarer Pathologie entnommen, um Histologie und Zellaktivität zu untersuchen. Aus solchen Proben lässt sich jedoch noch viel mehr Information gewinnen. Osteogenesis imperfecta (OI) ist eine genetisch und phänotypisch sehr heterogene Erkrankung. Mutationen betreffen Gene, die entweder für Kollagen selbst oder Proteine zur Kollagensynthese kodieren. Allen Formen von OI ist eine erhöhte Knochenbrüchigkeit gemeinsam. Die vorliegende Arbeit beschreibt, wie Knochenbiopsien eingesetzt wurden, um Veränderungen im Knochenmaterial auf die Spur zu kommen. Ein wesentliches Ergebnis war beispielsweise, dass bei OI der Mineralgehalt im Knochen unabhängig vom Schweregrad erhöht ist. Die Mineralpartikel im Kollagen sind bei OI normal groß oder sogar kleiner, aber dichter gepackt. Erst kürzlich konnte beobachtet werden, dass die Orientierung des Kollagens bei bestimmten Formen der OI hochgradig gestört ist. Diese Materialuntersuchungen weisen darauf hin, dass der Verbund aus Kollagen und Mineralpartikel im Knochenmaterial bei OI deutlich verändert ist und tragen zur Erklärung der reduzierten mechanischen Festigkeit des Materials bei.

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Acknowledgements

The authors would like to thank colleagues and collaborators for past and ongoing exciting scientific work, in particular, Prof. Dr. Klaus Klaushofer and PD Dr. Paul Roschger, Ludwig Boltzmann-Institute of Osteology in Vienna, Austria; PD Dr. Wolfgang Wagermaier and Prof. Dr. Peter Fratzl, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany; Prof. Dr. Frank Rauch and Prof. Dr. Francis H. Glorieux, Shriner’s Hospital for Children and McGill University, Montreal, Canada; Dr. Joan C. Marini, Section on Heritable Disorders, of Bone and Extracellular Matrix, NICHD, NIH Bethesda, MD, USA; and Prof. Dr. Wolfgang Högler, Universitätsklinik für Kinder- und Jugendheilkunde, Kepler Universitätsklinikum Linz, Austria. Sample preparations and bone analyzes are always very carefully performed by Sonja Lueger, Petra Keplinger, Daniela Gabriel and Phaedra Messmer at the Bone laboratory of the Ludwig Boltzmann Institute for Osteology. Our work would not have been possible without the continuous support of the AUVA (Research funds of the Austrian worker’s compensation board), the OEGK (Austrian Health Insurance Fund, former WGKK) and the Ludwig Boltzmann Society.

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Correspondence to PD Dr. Nadja Fratzl-Zelman.

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M. Mähr, S. Blouin, B.M. Misof, E.P. Paschalis, M.A. Hartmann, J. Zwerina and N. Fratzl-Zelman declare that they have no competing interests.

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Mähr, M., Blouin, S., Misof, B.M. et al. Bone properties in osteogenesis imperfecta: what can we learn from a bone biopsy beyond histology?. Wien Med Wochenschr 171, 111–119 (2021). https://doi.org/10.1007/s10354-021-00818-w

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Keywords

  • Rare bone diseases
  • Transiliac bone biopsies
  • Histomorphometry
  • Bone material quality
  • Bone matrix mineralization

Schlüsselwörter

  • Seltene Knochenerkrankungen
  • Transiliakale Knochenbiopsien
  • Histomorphometrie
  • Qualität des Knochenmaterials
  • Knochenmineralisierung