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J Pharm Pharm Sci. 2013;16(1):52-64.

Compositional and material properties of rat bone after bisphosphonate and/or Strontium ranelate drug treatment.

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1
Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.

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±10 mm(3)) compared with OVX-RIS (169±22 mm(3)), OVX-SrR (145±2 mm(3)), and OVX-RIS+SrR (172±8 mm(3)). 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.

PMID:
23683605
[Indexed for MEDLINE]
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