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Detecting early bone changes using in vivo micro-CT in ovariectomized, zoledronic acid-treated, and sham-operated rats

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Abstract

Summary

This study monitored in vivo the effect on bone microarchitecture of initiating antiresorptive treatment with zoledronic acid in rats at 2 weeks following ovariectomy, an early phase at which major degenerative bone changes have been found to occur. The treatment still facilitated the full reversal of cancellous bone loss in rat tibia, highlighting the importance of the time point of initiation of antiresorptive treatment.

Introduction

Injection of zoledronic acid in rats at time of ovariectomy has been found to fully preserve tibial bone microarchitecture over time, whereas injection at 8 weeks after ovariectomy has shown partial bone recovery. This study investigated the effect on microarchitecture of initiating antiresorptive treatment in the early phase following ovariectomy, at 2 weeks, a time point at which major degenerative changes in the bone have been found to occur.

Methods

Female Sprague–Dawley rats were divided into ovariectomized group, ovariectomized group treated with zoledronic acid, and sham-operated group. In vivo micro-CT scanning of rat tibiae and morphometric analysis were performed at 0, 2, 4, 8, and 12 weeks after ovariectomy, with zoledronic acid treatment beginning 2 weeks after ovariectomy. Data were first analyzed with repeated measures analysis of variance (longitudinal study design) and then without repeated measures (cross-sectional study design).

Results

The ovariectomized group demonstrated dramatic bone loss, first detected at week 2. Conversely, at week 4, the zoledronic acid-treated group returned microstructural parameters to baseline values. Remarkable increases in bone parameters were found after 6 weeks of treatment and maintained similar to sham group until the end. The longitudinal study design provided earlier detection of bone changes compared to the cross-sectional study design.

Conclusions

Treatment with zoledronic acid as late as 2 weeks after ovariectomy still facilitates the full reversal of cancellous bone loss in the rat tibia.

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Acknowledgments

Funding for this work was provided by a grant from the Australian Research Council (DP0663271).

Conflicts of interest

Dr. Phil Salmon is an employee at Skyscan NV, Belgium. All the other authors have no conflicts of interest.

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Authors and Affiliations

  1. Bone and Joint Research Laboratory, Surgical Pathology, SA Pathology and Hanson Institute, Frome Road, Adelaide, 5000, Australia

    E. Perilli, V. Le, B. Ma & N. L. Fazzalari

  2. Discipline of Pathology, University of Adelaide, Adelaide, Australia

    E. Perilli, V. Le, B. Ma & N. L. Fazzalari

  3. Vision Lab, Department of Physics, University of Antwerp, Antwerp, Belgium

    E. Perilli

  4. Skyscan NV, Kontich, Belgium

    P. Salmon

  5. School of Computer Science, Engineering & Mathematics, Flinders University, Adelaide, Australia

    K. Reynolds

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  1. E. Perilli
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Correspondence to E. Perilli.

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Perilli, E., Le, V., Ma, B. et al. Detecting early bone changes using in vivo micro-CT in ovariectomized, zoledronic acid-treated, and sham-operated rats. Osteoporos Int 21, 1371–1382 (2010). https://doi.org/10.1007/s00198-009-1082-z

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