Effects of bisphosphonate treatment on circulating osteogenic endothelial progenitor cells in postmenopausal women

Mayo Clin Proc. 2013 Jan;88(1):46-55. doi: 10.1016/j.mayocp.2012.08.019. Epub 2012 Dec 8.

Abstract

Objective: To evaluate whether bisphosphonates modulate vascular calcification by a modification in endothelial progenitor cells (EPCs) coexpressing osteoblastic surface markers and genes.

Patients and 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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Bone Density / drug effects
  • Bone Density Conservation Agents / therapeutic use*
  • C-Reactive Protein / metabolism
  • Calcium / blood
  • Creatinine / blood
  • Double-Blind Method
  • Down-Regulation
  • Endothelium / cytology
  • Endothelium / drug effects*
  • Endothelium / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Etidronic Acid / analogs & derivatives*
  • Etidronic Acid / therapeutic use
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-8 / blood
  • Middle Aged
  • Osteoblasts / metabolism
  • Osteogenesis / drug effects
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / genetics*
  • Osteoprotegerin / blood
  • Phosphorus / blood
  • Placebos
  • RANK Ligand / blood
  • Risedronic Acid
  • Stem Cells / drug effects*
  • Stem Cells / metabolism
  • Treatment Outcome
  • Vitamin D / blood

Substances

  • Biomarkers
  • Bone Density Conservation Agents
  • Interleukin-8
  • Osteoprotegerin
  • Placebos
  • RANK Ligand
  • Vitamin D
  • Phosphorus
  • C-Reactive Protein
  • Creatinine
  • Risedronic Acid
  • Etidronic Acid
  • Calcium