| Effect of bisphosphonates on vascular calcification and bone metabolism in experimental renal failure. | |
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MedLine Citation:
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PMID: 19129793 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although it is known that bisphosphonates prevent medial vascular calcification in vivo, their mechanism of action remains unknown and, in particular, whether they act directly on the blood vessels or indirectly through inhibition of bone resorption. To determine this, we studied the effects of two bisphosphonates on calcification of rat aortas in vitro and on in vivo aortic calcification and bone metabolism in rats with renal failure. We produced vascular calcification in rats with adenine-induced renal failure fed a high-phosphate diet. Daily treatment with either etidronate or pamidronate prevented aortic calcification, with the latter being 100-fold more potent. Both aortic calcification and bone formation were reduced in parallel; however, bone resorption was not significantly affected. In all uremic rats, aortic calcium content correlated with bone formation but not with bone resorption. Bisphosphonates also inhibited calcification of rat aortas in culture and arrested further calcification of precalcified vessels but did not reverse their calcification. Expression of osteogenic factors or calcification inhibitors was not altered by etidronate in vitro. Hence, these studies show that bisphosphonates can directly inhibit uremic vascular calcification independent of bone resorption. The correlation between inhibition of aortic calcification and bone mineralization is consistent with a common mechanism such as the prevention of hydroxyapatite formation and suggests that bisphosphonates may not be able to prevent vascular calcification without inhibiting bone formation in uremic rats. |
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Authors:
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Koba A Lomashvili; Marie-Claude Monier-Faugere; Xiaonan Wang; Hartmut H Malluche; W Charles O'Neill |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-01-07 |
Journal Detail:
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Title: Kidney international Volume: 75 ISSN: 1523-1755 ISO Abbreviation: Kidney Int. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-02-27 Completed Date: 2009-05-18 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
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Languages: eng Pagination: 617-25 Citation Subset: IM |
Affiliation:
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Renal Division, Emory University School of Medicine, Atlanta, Georgia 30322, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aortic Diseases / pathology Bone Resorption Bone and Bones / metabolism Calcification, Physiologic / drug effects* Calcinosis / prevention & control* Diphosphonates / adverse effects, pharmacology*, therapeutic use Etidronic Acid / adverse effects, therapeutic use Rats Uremia / complications |
| Grant Support | |
ID/Acronym/Agency:
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DK069681/DK/NIDDK NIH HHS; R01 DK069681-03/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Diphosphonates; 2809-21-4/Etidronic Acid; 40391-99-9/pamidronate |
| Comments/Corrections | |
Comment In:
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Kidney Int. 2009 Mar;75(6):580-2
[PMID:
19247382
]
Kidney Int. 2009 Jun;75(12):1355-6; author reply 1356 [PMID: 19483753 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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