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Temporal Changes in Bone Composition, Architecture, and Strength Following Estrogen Deficiency in Osteoporosis

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Abstract

Using an ovariectomized (OVX) ovine model, we provide an analysis of the timing of changes in bone following estrogen deficiency. The expression of genes known to regulate osteoclastogenesis, matrix production, and mineralization, as measured by real-time RT-PCR, was significantly increased by 12 months; and increased expression was maintained through to 31 months post-OVX compared to controls. FTIR spectroscopy confirmed that mineralized crystals were less mature than in controls 12 months post-OVX and were even less so by 31 months. The mineral-to-matrix ratio was significantly reduced by 31 months, while the ratio of mature to immature collagen cross-linking was initially increased at 12 months and subsequently reduced at 31 months post-OVX. In contrast, trabecular number, thickness, and separation were unchanged at 12 months. Significant reductions in trabecular number and thickness and a significant increase in trabecular separation were observed 31 months after OVX. Most notably perhaps these combined changes led to a significant reduction in the compressive strength of trabecular bone after 31 months. The results indicate that there is an initial increase in bone turnover, which is accompanied by a change in bone composition. This is followed by a continued increase in bone resorption and relative reduction in bone formation, leading to deterioration in bone microarchitecture. Ultimately, these cumulative changes led to a significant reduction in the compressive strength of bones following 31 months of estrogen deficiency. These findings provide important insight into the time sequence of changes during osteoporosis.

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Acknowledgement

The authors acknowledge Dr. Gerald Atkins for helpful discussion and Ms. Lena Truong, Ms. Katie Reeve-Arnold, and Ms. Laura Corrigan for technical assistance. Funding for this study was granted by the Health Research Board under grant numbers RP/2004/229 and RP/2007/179 and by the Higher Education Authority in Ireland under PRTLI Cycle III.

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Authors and Affiliations

  1. Department of Anatomy, Royal College of Surgeons in Ireland, 123, St. Stephen’s Green, Dublin 2, Ireland

    Orlaith Brennan, T. Clive Lee & Fergal J. O’Brien

  2. Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland

    Orlaith Brennan, T. Clive Lee & Fergal J. O’Brien

  3. Bone and Joint Research Laboratory, SA Pathology and Hanson Institute, Adelaide, SA, Australia

    Orlaith Brennan, Julia S. Kuliwaba, Ian H. Parkinson & Nicola L. Fazzalari

  4. Discipline of Anatomy and Pathology, The University of Adelaide, Adelaide, SA, Australia

    Julia S. Kuliwaba, Ian H. Parkinson & Nicola L. Fazzalari

  5. Department of Mechanical and Biomedical Engineering, National University of Ireland Galway, Galway, Ireland

    Laoise M. McNamara

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  1. Orlaith Brennan
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Correspondence to Fergal J. O’Brien.

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Brennan, O., Kuliwaba, J.S., Lee, T.C. et al. Temporal Changes in Bone Composition, Architecture, and Strength Following Estrogen Deficiency in Osteoporosis. Calcif Tissue Int 91, 440–449 (2012). https://doi.org/10.1007/s00223-012-9657-7

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  • DOI: https://doi.org/10.1007/s00223-012-9657-7

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