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Comparative Effect of Zoledronic Acid Versus Denosumab on Serum Sclerostin and Dickkopf-1 Levels of Naive Postmenopausal Women With Low Bone Mass: A Randomized, Head-to-head Clinical Trial.
MedLine Citation:
PMID:  23788684     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Context:Decreased bone formation due to coupling effect limits bone mass increases following antiresorptive treatment.Objective:To compare the effects of two potent antiresorptive agents with different mechanism of action on serum levels of Wnt antagonists, sclerostin and dickkopf (Dkk)-1.Design:Interventional, parallel assignment, open label, randomized clinical trial.Setting:The study was conducted at the outpatient clinics for Metabolic Bone Diseases of 424 General Military Hospital, Thessaloniki, Greece.Patients and Interventions:Treatment naïve postmenopausal women with low bone mass were assigned to zoledronic acid infusion (n=46) or denosumab injection (n=46). One woman of the zoledronic acid group was lost to follow-up.Main outcome measures:Serum sclerostin and Dkk-1 levels. Secondary measurements: serum osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL), procollagen type 1 N-terminal propeptide (P1NP) and C-terminal cross-linking telopeptide of type 1 collagen (CTx).Results:Serum sclerostin levels significantly decreased in the zoledronic acid (p<0.001), whereas increased in the denosumab group (p=0.003). Dkk-1 levels significantly decreased in the zoledronic acid (p=0.006), but did not change in the denosumab group (p=0.402). Serum OPG remained essentially unchanged in either group, whereas RANKL decreased in zoledronic acid (p=0.004), but increased in denosumab group (p=0.037). Bone markers (P1NP, CTx and TSAP) decreased in both groups (all p<0.001).Conclusions:Although they both decrease bone resorption, zoledronic acid and denosumab exert an opposite effect on Wnt signaling: the former decreases serum levels of both sclerostin and Dkk-1, while the latter increases sclerostin and does not affect Dkk-1.
Authors:
Athanasios D Anastasilakis; Stergios A Polyzos; Athina Gkiomisi; Ilias Bisbinas; Spyridon Gerou; Polyzois Makras
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-6-20
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-6-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece;
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