Compositional and Material Properties of Rat Bone after Bisphosphonate and/or Strontium Ranelate Drug Treatment

Authors

  • Yuchin Wu
  • Samer M Adeeb
  • M. John Duke
  • David Munoz-Paniagua
  • Michael R. Doschak

DOI:

https://doi.org/10.18433/J3C59H

Abstract

Purpose. We investigated elemental strontium and/or bisphosphonate drug incorporation upon the compositional and biomechanical properties of vertebral bone, in a rat model of Osteoporosis secondary to ovariectomy. Methods. Six month old female rats were ovariectomized (OVX) and divided into untreated OVX-Vehicle, OVX-RIS (Risedronate bisphosphonate [BP] treated), OVX-SrR (Strontium Ranelate [Protos®] treated), combination OVX-RIS+SrR, and sham-operated controls. After 16 weeks of treatment, rats were euthanized and lumbar vertebra were dissected. Micro-Computed Tomography (micro-CT), Electron Probe Micro-Analysis (EPMA), mechanical testing in compression and nano-indentation testing were then undertaken to evaluate bone morphometry, elemental composition, material properties and strength. Results. Bone Volume was significantly reduced in the OVX-Vehicle (133±10mm3) compared with OVX-RIS (169±22mm3), OVX-SrR (145±2mm3), and OVX-RIS+SrR (172±8mm3). EPMA mapped elemental Sr deposition to the periosteal surface of cortical bone (50-100 µm thick), endosteal trabecular surfaces (20 µm thick), as well as to both vertebral growth plates. The atomic ratios of (Ca+Sr)/P were significantly reduced with SrR treatment (2.4%-6.6%), indicating Sr incorporation into bone mineral. No significant differences were measured in vertebral bone reduced modulus by nano-indentation. Conversely, all BP-dosed groups had significantly increased structural bone strength. Conclusions. Thus, we conclude that BP drugs dominate the conservation of trabecular geometry and structural strength in OP rats, whereas Sr drugs likely influence bone volume and material composition locally. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Author Biographies

Yuchin Wu

Department of Biomedical Engineering,University of Alberta

Samer M Adeeb

Civil & Environmental Engineering,University of Alberta

M. John Duke

Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta

David Munoz-Paniagua

National Research Council - National Institute for Nanotechnology

Michael R. Doschak

Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta

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Published

2013-01-28

How to Cite

Wu, Y., Adeeb, S. M., Duke, M. J., Munoz-Paniagua, D., & Doschak, M. R. (2013). Compositional and Material Properties of Rat Bone after Bisphosphonate and/or Strontium Ranelate Drug Treatment. Journal of Pharmacy & Pharmaceutical Sciences, 16(1), 52–64. https://doi.org/10.18433/J3C59H

Issue

Section

Pharmaceutical Sciences; Review Articles