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

  1. Get@NRC: Compositional and material properties of rat bone after bisphosphonate and/or strontium ranelate drug treatment (Opens in a new window)
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Journal titleJournal of Pharmacy and Pharmaceutical Sciences
Pages5264; # of pages: 13
Subjectcalcium; phosphorus; risedronic acid; strontium; strontium ranelate; animal experiment; animal model; animal tissue; article; biomechanics; bone mass; bone strength; bone structure; combination chemotherapy; composite material; compressive strength; controlled study; cortical bone; drug efficacy; drug mechanism; electron probe microanalysis; female; growth plate; lumbar vertebra; micro-computed tomography; monotherapy; nonhuman; osteoporosis; ovariectomy; periosteum; rat; trabecular bone; treatment duration; Young modulus; Animals; Bone and Bones; Bone Density Conservation Agents; Calcium; Diphosphonates; Female; Hardness Tests; Osteoporosis; Ovariectomy; Phosphorus; Rats; Rats, Sprague-Dawley; Strontium; Thiophenes; X-Ray Microtomography
AbstractPurpose. 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 OVXVehicle, 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), OVXSrR (145±2mm3), and OVX-RIS+SrR (172±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.
Publication date
AffiliationNational Research Council Canada (NRC-CNRC); National Institute for Nanotechnology (NINT-INNT)
Peer reviewedYes
NPARC number21269613
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Record identifier2ed26931-e133-4c1f-bc5e-37b699213a71
Record created2013-12-13
Record modified2016-05-09
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