Monitoring the degradation of bone elastic properties induced by microgravity: a proposal.

Background Important alterations occurring in living organisms during space flight concern the trabecular compartment of load-bearing bones, and result in significant bone mineral loss and decay of mechanical properties [1, 2]. Composition, mineral content, and the complex micro-scale trabecular microarchitecture contribute together to the macro-scale functional strength of bone as a whole [3]. Bone alterations, including those due to reduced gravitational load conditions, are mainly assessed by measuring bone density, even though, alone, it cannot comprehensively assess skeletal integrity [4]. Micro-tomographic techniques [5], not suitable for monitoring, allow for a pre- and post-mission examination of the trabecular bone component, which undergoes the fastest and most important alterations, placing astronauts at serious risk of fracture upon re-entry [5]. Mesoscale studies in modeled microgravity conditions combined with numerical simulations, show that degradation of apparent mechanical properties must be considered to achieve an accurate description of bone performance [6, 7]. To quantify the pathological alterations in the bone micro-architecture in a clinical setting, a patented, CE marked, software medical device, the Bone Elastic Structure Test, BES TEST, has been developed. Results are uncorrelated to BMD and independent of load [8, 9]. BES TEST has a diagnostic accuracy of 78% as a 3-year fracture risk estimator [10] and can be used to complete the densitometry picture and as monitoring tool for bone follow-up in in rheumatology [9], oncology [11], nephrology [12] and rare bone diseases [13]. Its prospective application for bone alteration monitoring during spaceflights is discussed. Method BES TEST simulates the application of forces on an X-ray functional biopsy of the patient’s hand [14-19]. Results are combined in an index, BSI, and its T-score and Z-score (Fig.1). Characteristics: X-ray dose < 0.0005 µSV; CV intra-operator=0.06; 95%CI±8 BSI; CV inter-operator =0.11; 95% CI=±10.8 BSI [20, 21], in line with the diagnostic gold standard. Requirements for investigation of BES TEST space application: - Acquisition: x-ray scanner, small detector. Several possible arrangements are possible, tests in simulated space flight will clarify the best configuration. - Calibration: the acquisition set-up will likely differ from the clinical one. - Analysis: radiograms upload to automatic service. Results BES TEST monitors trabecular bone, which changes more rapidly than cortical bone and BMD in response to physio-pathological alterations, like those occurring during spaceflight. Conclusion BESTEST is fast, easy to perform, cost-effective and can be significantly repeated within just weeks, showing potential for monitoring the changes in bone functionality during long-duration space missions. Acknowledgements Area Science Park financially supported the development of this work at various stages. References 1. Vico, L. et al. Bone. 1998. 2. Lang, T. et al. J Bone and Mineral Research. 2004. 3. Kleerekoper, M. et al. Calcif Tissue Int. 1985. 4. J.D. Sibonga et al. Aerosp.Med.Hum. perform. 2015. 5. J.D. Sibonga et al. J. Clin. Densitom. 2020. 6. Cosmi F. et al. J. Mech. Behav. Biomed. Mater. 2009 7. Francesca Cosmi et al. J. Mech. Behav. Biomed. Mater. 2015 8. Cosmi F et al. Mater Today: Proc. 2018. 9. Saviola G. et al. Minerva Medica. 2019. 10. Francesca Cosmi et al. 2023. 11. S. Saracchini et al. 2019. 12. M. Ferraro et al. NDT. 2021. 13. Cosmi F and Maximova N. Mater. Today. 2019 14. Wilczek M. L et al. Eur Radiol. 2013. 15. Albanese CV et al. R. Radiol Med. 2011. 16. Alenfeld FE et al. Osteoporosis Int. 1998. 17. Mele R. Osteoporos Int. 1997. 18. Tonti E. Computer Modeling in Engineering and Science. 2001. 19. Cosmi F. Molecular and Cellular Biology. 2015. 20. Cosmi F. et al. Proc IMechE Part C. 2022. 21. Cosmi F. et al. Proc IMechE Part C. 2023.