Original Research

Calcified Tissue International

, Volume 91, Issue 6, pp 440-449

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

  • Orlaith BrennanAffiliated withDepartment of Anatomy, Royal College of Surgeons in IrelandTrinity Centre for Bioengineering, Trinity College DublinBone and Joint Research Laboratory, SA Pathology and Hanson Institute
  • , Julia S. KuliwabaAffiliated withBone and Joint Research Laboratory, SA Pathology and Hanson InstituteDiscipline of Anatomy and Pathology, The University of Adelaide
  • , T. Clive LeeAffiliated withDepartment of Anatomy, Royal College of Surgeons in IrelandTrinity Centre for Bioengineering, Trinity College Dublin
  • , Ian H. ParkinsonAffiliated withBone and Joint Research Laboratory, SA Pathology and Hanson InstituteDiscipline of Anatomy and Pathology, The University of Adelaide
  • , Nicola L. FazzalariAffiliated withBone and Joint Research Laboratory, SA Pathology and Hanson InstituteDiscipline of Anatomy and Pathology, The University of Adelaide
  • , Laoise M. McNamaraAffiliated withDepartment of Mechanical and Biomedical Engineering, National University of Ireland Galway
  • , Fergal J. O’BrienAffiliated withDepartment of Anatomy, Royal College of Surgeons in IrelandTrinity Centre for Bioengineering, Trinity College Dublin Email author 

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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.

Keywords

Osteoporosis Microarchitecture Bone composition Biomechanical property Animal model