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 withplacebo 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.
RCT Entities:
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.
Authors: Sammy Elmariah; Joseph A C Delaney; Kevin D O'Brien; Matthew J Budoff; Jens Vogel-Claussen; Valentin Fuster; Richard A Kronmal; Jonathan L Halperin Journal: J Am Coll Cardiol Date: 2010-11-16 Impact factor: 24.094
Authors: Mario Gössl; Ulrike I Mödder; Elizabeth J Atkinson; Amir Lerman; Sundeep Khosla Journal: J Am Coll Cardiol Date: 2008-10-14 Impact factor: 24.094
Authors: Koba A Lomashvili; Marie-Claude Monier-Faugere; Xiaonan Wang; Hartmut H Malluche; W Charles O'Neill Journal: Kidney Int Date: 2009-01-07 Impact factor: 10.612
Authors: John T Chow; Sundeep Khosla; L Joseph Melton; Elizabeth J Atkinson; Jon J Camp; Ann E Kearns Journal: J Bone Miner Res Date: 2008-10 Impact factor: 6.741
Authors: C J Dunn; L A Galinet; H Wu; R A Nugent; S T Schlachter; N D Staite; D G Aspar; G A Elliott; N A Essani; N A Rohloff Journal: J Pharmacol Exp Ther Date: 1993-09 Impact factor: 4.030
Authors: Koji Fujita; Matthew M Roforth; Susan Demaray; Ulrike McGregor; Salman Kirmani; Louise K McCready; James M Peterson; Matthew T Drake; David G Monroe; Sundeep Khosla Journal: J Clin Endocrinol Metab Date: 2013-12-20 Impact factor: 5.958
Authors: K Fujita; M M Roforth; E J Atkinson; J M Peterson; M T Drake; L K McCready; J N Farr; D G Monroe; S Khosla Journal: Osteoporos Int Date: 2013-10-11 Impact factor: 4.507
Authors: John S Manavalan; Stephen Arpadi; Shenthuraan Tharmarajah; Jayesh Shah; Chiyuan A Zhang; Marc Foca; Natalie Neu; David L Bell; Kyle K Nishiyama; Stavroula Kousteni; Michael T Yin Journal: J Bone Miner Res Date: 2016-07-06 Impact factor: 6.741
Authors: Matthew M Roforth; Koji Fujita; Ulrike I McGregor; Salman Kirmani; Louise K McCready; James M Peterson; Matthew T Drake; David G Monroe; Sundeep Khosla Journal: Bone Date: 2013-10-29 Impact factor: 4.398