title: A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.
abstract: The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Neven
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Tineke M
authors.initials: TM
authors.lastname: De Schutter
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Dams
authors.affiliation: Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Gundlach
authors.affiliation: Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Steppan
authors.affiliation: Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Büchel
authors.affiliation: Department of Nephrology, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Passlick-Deetjen
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: D'Haese
authors.affiliation: Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Geert J
authors.initials: GJ
authors.lastname: Behets
mesh_terms: D000085:Acetates / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D017610:Calcium Compounds / Q000378:metabolism / Q000494:pharmacology; D004032:Diet; D004195:Disease Models, Animal; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D061205:Vascular Calcification / Q000378:metabolism*
chemical_list: D000085:Acetates; D015415:Biomarkers; D017610:Calcium Compounds; D010710:Phosphates; C005479:magnesium carbonate; D010758:Phosphorus; D008274:Magnesium; C120662:calcium acetate