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Effects of Bisphosphonate Treatment on Circulating Osteogenic Endothelial Progenitor Cells in Postmenopausal Women

Published:December 10, 2012DOI:https://doi.org/10.1016/j.mayocp.2012.08.019

      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.

      Abbreviations and Acronyms:

      AP (alkaline phosphatase), CTx (carboxyterminal telopeptide of type 1 collagen), CV (coefficient of variation), ELISA (enzyme-linked immunosorbent assay), EPC (endothelial progenitor cell), hs-CRP (high-sensitivity C-reactive protein), IL (interleukin), IQR (interquartile range), KDR (vascular endothelial growth factor 2/kinase insert domain receptor), P1NP (aminoterminal propeptide of type 1 procollagen), RANKL (receptor activator of nuclear factor κB ligand), TRAP5b (tartrate-resistant acid phosphatase 5b)
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