title: Compositional and material properties of rat bone after bisphosphonate and/or Strontium ranelate drug treatment.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Yuchin
authors.initials: Y
authors.lastname: Wu
authors.forename: Samer M
authors.initials: SM
authors.lastname: Adeeb
authors.forename: M John
authors.initials: MJ
authors.lastname: Duke
authors.forename: David
authors.initials: D
authors.lastname: Munoz-Paniagua
authors.forename: Michael R
authors.initials: MR
authors.lastname: Doschak
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001842:Bone and Bones / Q000737:chemistry / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006245:Hardness Tests; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism; D010052:Ovariectomy; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013324:Strontium / Q000378:metabolism; D013876:Thiophenes / Q000008:administration & dosage*; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D013876:Thiophenes; C081587:strontium ranelate; D010758:Phosphorus; D002118:Calcium; D013324:Strontium