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Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis

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Abstract

Recently, it has been shown that transient bone biology can be observed in vivo using time-lapse micro-computed tomography (μCT) in the mouse tail bone. Nevertheless, in order for the mouse tail bone to be a model for human disease, the hallmarks of any disease must be mimicked. The aim of this study was to investigate whether postmenopausal osteoporosis could be modeled in caudal vertebrae of C57Bl/6 mice, considering static and dynamic bone morphometry as well as mechanical properties, and to describe temporal changes in bone remodeling rates. Twenty C57Bl/6 mice were ovariectomized (OVX, n = 11) or sham-operated (SHM, n = 9) and monitored with in vivo μCT on the day of surgery and every 2 weeks after, up to 12 weeks. There was a significant decrease in bone volume fraction for OVX (−35%) compared to SHM (+16%) in trabecular bone (P < 0.001). For OVX, high-turnover bone loss was observed, with the bone resorption rate exceeding the bone formation rate (P < 0.001). Furthermore there was a significant decrease in whole-bone stiffness for OVX (−16%) compared to SHM (+11%, P < 0.001). From these results we conclude that the mouse tail vertebra mimics postmenopausal bone loss with respect to these parameters and therefore might be a suitable model for postmenopausal osteoporosis. When evaluating temporal changes in remodeling rates, we found that OVX caused an immediate increase in bone resorption rate (P < 0.001) and a delayed increase in bone formation rate (P < 0.001). Monitoring transient bone biology is a promising method for future research.

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Acknowledgements

The authors gratefully acknowledge funding from the European Union for the Osteoporotic Virtual Physiological Human Project (FP7-ICT2008-223865), funding from the Whitaker Foundation, and computational time from the Swiss National Supercomputing Center (CSCS, Manno, Switzerland). We thank Peter Schwilch and Marco Hitz for technical assistance with the mouse holder and the statistical consulting team offered by the Seminar for Statistics at the ETH Zurich.

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  1. Institute for Biomechanics, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093, Zürich, Switzerland

    Floor M. Lambers, Gisela Kuhn, Friederike A. Schulte, Kathleen Koch & Ralph Müller

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  1. Floor M. Lambers
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Correspondence to Ralph Müller.

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Lambers, F.M., Kuhn, G., Schulte, F.A. et al. Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis. Calcif Tissue Int 90, 108–119 (2012). https://doi.org/10.1007/s00223-011-9553-6

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