title: Effects of bisphosphonate treatment on circulating osteogenic endothelial progenitor cells in postmenopausal women.
abstract: OBJECTIVE
  To evaluate whether bisphosphonates modulate vascular calcification by a modification in endothelial progenitor cells (EPCs) coexpressing osteoblastic surface markers and genes.
  
  
  METHODS
  We performed a double-blind, randomized study of 20 healthy, early postmenopausal women (from February 1, 2008, through July 31, 2008) treated with placebo or risedronate sodium (35 mg/wk) for 4 months. Peripheral blood was collected at baseline and 4 months to determine serum inflammatory markers, osteoprotegerin, and receptor activator of nuclear factor-κB ligand levels and bone turnover markers. Peripheral blood mononuclear cells were stained for EPC surface markers (CD34, CD133, and vascular endothelial growth factor receptor/kinase insert domain receptor) and osteoblast markers (osteocalcin, alkaline phosphatase, and Stro-1).
  
  
  RESULTS
  Risedronate treatment resulted in a significant down-regulation of gene sets for osteoblast differentiation and proliferation in EPCs with a trend of decreasing EPCs coexpressing osteocalcin.
  
  
  CONCLUSIONS
  Our findings indicate that bisphosphonate treatment down-regulates the expression of osteogenic genes in EPCs and suggest a possible mechanism by which bisphosphonates may inhibit vascular calcification.
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA.
authors.forename: Pilar
authors.initials: P
authors.lastname: Peris
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Atkinson
authors.forename: Mario
authors.initials: M
authors.lastname: Gössl
authors.forename: Trevor L
authors.initials: TL
authors.lastname: Kane
authors.forename: Louise K
authors.initials: LK
authors.lastname: McCready
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Ulrike I
authors.initials: UI
authors.lastname: McGregor
mesh_terms: D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D015536:Down-Regulation; D004727:Endothelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000235:genetics*; D053244:Osteoprotegerin / Q000097:blood; D010758:Phosphorus / Q000097:blood; D010919:Placebos; D053245:RANK Ligand / Q000097:blood; D000068296:Risedronic Acid; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome; D014807:Vitamin D / Q000097:blood
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D016209:Interleukin-8; D053244:Osteoprotegerin; D010919:Placebos; D053245:RANK Ligand; D014807:Vitamin D; D010758:Phosphorus; D002097:C-Reactive Protein; D003404:Creatinine; D000068296:Risedronic Acid; D012968:Etidronic Acid; D002118:Calcium