Document Detail

Fluvastatin does not prevent the acute-phase response to intravenous zoledronic acid in post-menopausal women.
MedLine Citation:
PMID:  21047568     Owner:  NLM     Status:  MEDLINE    
The acute-phase response (APR) to aminobisphosphonates is triggered by activation of γδ T cells, resulting in pro-inflammatory cytokine release. Statins prevent aminobisphosphonate-induced γδ T cell activation in vitro, raising the possibility that statins might prevent the APR in vivo. The objective of this study was to determine whether fluvastatin prevents the APR to zoledronic acid in post-menopausal women. A double-blind, randomised, placebo-controlled study was conducted in 60 healthy, post-menopausal, female volunteers (mean age 60.6 ± 4.0). Volunteers received 5 mg zoledronic acid by intravenous infusion, and either three times 40 mg fluvastatin (0 hr, 24 hr and 48 hr), 40 mg fluvastatin (0 hr) plus placebo (24 hr and 48 hr), or placebo (0 hr, 24 hr and 48 hr), orally. Post-infusion symptoms were assessed by questionnaire. Changes in γδ T cell levels, pro-inflammatory cytokines (TNFα, IFNγ, IL-6) and C-reactive protein (CRP) were measured in peripheral blood at various time-points post-infusion. Zoledronic acid administration triggered increased serum levels of TNFα, IFNγ, IL-6 and CRP in ≥70% of study volunteers, whilst characteristic APR symptoms were observed in >50% of participants. Zoledronic acid also induced a transient fall in circulating Vγ9Vδ2 T cell levels at 48 hr, consistent with Vγ9Vδ2 T cell activation. Concurrent fluvastatin administration did not prevent zoledronic acid-induced cytokine release, alter circulating Vγ9Vδ2 T cell levels, nor diminish the frequency or severity of APR symptoms. In conclusion, intravenous zoledronic acid induced pro-inflammatory cytokine release and APR symptoms in the majority of study participants, which was not prevented by co-administration of fluvastatin.
Keith Thompson; Fran Keech; David J McLernon; Kumar Vinod; Robin J May; William G Simpson; Michael J Rogers; David M Reid
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-10-31
Journal Detail:
Title:  Bone     Volume:  49     ISSN:  1873-2763     ISO Abbreviation:  Bone     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-13     Completed Date:  2011-09-28     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  8504048     Medline TA:  Bone     Country:  United States    
Other Details:
Languages:  eng     Pagination:  140-5     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Acute-Phase Reaction / complications,  drug therapy*,  prevention & control*
Anticholesteremic Agents / pharmacology,  therapeutic use
Bone Density Conservation Agents / pharmacology,  therapeutic use
Bone Resorption / blood,  complications,  drug therapy
Cholesterol / blood
Cytokines / blood
Diphosphonates / administration & dosage*,  pharmacology,  therapeutic use*
Fatty Acids, Monounsaturated / administration & dosage,  pharmacology*,  therapeutic use*
Imidazoles / administration & dosage*,  pharmacology,  therapeutic use*
Indoles / administration & dosage,  pharmacology*,  therapeutic use*
Injections, Intravenous
Middle Aged
Postmenopause / blood,  drug effects*
T-Lymphocytes / drug effects
Grant Support
18439//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Bone Density Conservation Agents; 0/Cytokines; 0/Diphosphonates; 0/Fatty Acids, Monounsaturated; 0/Imidazoles; 0/Indoles; 118072-93-8/zoledronic acid; 4L066368AS/fluvastatin; 97C5T2UQ7J/Cholesterol

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