How osteons form: A quantitative hypothesis-testing analysis of cortical pore filling and wall asymmetry

Hegarty-Cremer, S. G.; Borggaard, X. G.; Andreasen, C. M.; van der Eerden, B. C.; Simpson, M. J.; Andersen, T. L.; Buenzli, P. R.

doi:10.1101/2023.10.26.564273

bioRxiv · 10.1101/2023.10.26.564273

How osteons form: A quantitative hypothesis-testing analysis of cortical pore filling and wall asymmetry

Hegarty-Cremer, S. G.·Borggaard, X. G.·Andreasen, C. M.·van der Eerden, B. C.·Simpson, M. J.·Andersen, T. L.·Buenzli, P. R.

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Abstract

Osteon morphology provides valuable information about the interplay between different processes involved in bone remodelling. The correct quantitative interpretation of these morphological features is challenging due to the complexity of interactions between osteoblast behaviour, and the evolving geometry of cortical pores during pore closing. We present a combined experimental and mathematical modelling study to provide insights into bone formation mechanisms during cortical bone remodelling based on histological cross-sections of quiescent human osteons and hypothesis-testing analyses. We introduce wall thickness asymmetry as a measure of the local asymmetry of bone formation within an osteon and examine the frequency distribution of wall thickness asymmetry in cortical osteons from human iliac crest bone samples from women 16-78 years old. Our measurements show that most osteons possess some degree of asymmetry, and that the average degree of osteon asymmetry in cortical bone evolves with age. We then propose a comprehensive mathematical model of cortical pore filling that includes osteoblast secretory activity, osteoblast elimination, osteoblast embedment as osteocytes, and osteoblast crowding and redistribution along the bone surface. The mathematical model is first calibrated to symmetric osteon data, and then used to test three mechanisms of asymmetric wall formation against osteon data: (i) delays in the onset of infilling around the cement line; (ii) heterogeneous osteoblastogenesis around the bone perimeter; and (iii) heterogeneous osteoblast secretory rate around the bone perimeter. Our results suggest that wall thickness asymmetry due to off-centred Haversian pores within osteons, and that nonuniform lamellar thicknesses within osteons are important morphological features that can indicate the prevalence of specific asymmetry-generating mechanisms. This has significant implications for the study of disruptions of bone formation as it could indicate what biological bone formation processes may become disrupted with age or disease.

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Hegarty-Cremer, S. G., Borggaard, X. G., Andreasen, C. M., van der Eerden, B. C., Simpson, M. J., Andersen, T. L., Buenzli, P. R.. 2023-10-27. How osteons form: A quantitative hypothesis-testing analysis of cortical pore filling and wall asymmetry. https://doi.org/10.1101/2023.10.26.564273

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