Document Detail

Effect of bisphosphonates on vascular calcification and bone metabolism in experimental renal failure.
MedLine Citation:
PMID:  19129793     Owner:  NLM     Status:  MEDLINE    
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.
Koba A Lomashvili; Marie-Claude Monier-Faugere; Xiaonan Wang; Hartmut H Malluche; W Charles O'Neill
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-01-07
Journal Detail:
Title:  Kidney international     Volume:  75     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-27     Completed Date:  2009-05-18     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  617-25     Citation Subset:  IM    
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MeSH Terms
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
Uremia / complications
Grant Support
Reg. No./Substance:
0/Diphosphonates; M2F465ROXU/Etidronic Acid; OYY3447OMC/pamidronate
Comment In:
Kidney Int. 2009 Mar;75(6):580-2   [PMID:  19247382 ]
Kidney Int. 2009 Jun;75(12):1355-6; author reply 1356   [PMID:  19483753 ]

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