title: 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.
abstract: BACKGROUND
  Decreased bone formation due to a coupling effect limits bone mass increases after antiresorptive treatment.
  
  
  OBJECTIVE
  The purpose of this study was to compare the effects of 2 potent antiresorptive agents with different mechanism of action on serum levels of Wnt antagonists, sclerostin and dickkopf-1 (Dkk-1).
  
  
  METHODS
  This was an interventional, parallel assignment, open-label, randomized clinical trial.
  
  
  METHODS
  The study was conducted at the outpatient clinics for metabolic bone diseases of 424 General Military Hospital, Thessaloniki, Greece.
  
  
  METHODS
  Naive postmenopausal women with low bone mass were assigned to zoledronic acid infusion (n = 46) or denosumab injection (n = 46). One woman in the zoledronic acid group was lost to follow-up.
  
  
  METHODS
  Serum sclerostin and Dkk-1 levels were the main outcomes. Secondary measurements were serum osteoprotegerin, receptor activator of nuclear factor κB ligand, procollagen type 1 N-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen.
  
  
  RESULTS
  Serum sclerostin levels significantly decreased in the zoledronic acid (P < .001) but increased in the denosumab group (P = .003). Dkk-1 levels significantly decreased in the zoledronic acid group (P = .006) but did not change in the denosumab group (P = .402). Serum osteoprotegerin remained essentially unchanged in either group, whereas receptor activator of nuclear factor κB ligand decreased in the zoledronic acid group (P = .004) but increased in the denosumab group (P = .037). Bone markers (procollagen type 1 N-terminal propeptide, C-terminal cross-linking telopeptide of type 1 collagen, and total serum alkaline phosphatase) decreased in both groups (all P < .001).
  
  
  CONCLUSIONS
  Although they both decrease bone resorption, zoledronic acid and denosumab exert opposite effects on Wnt signaling: the former decreases serum levels of both sclerostin and Dkk-1, whereas the latter increases sclerostin and does not affect Dkk-1.
authors.affiliation: Department of Endocrinology, 424 General Military Hospital, 56429 Thessaloniki, Greece. anastath@endo.gr
authors.forename: Athanasios D
authors.initials: AD
authors.lastname: Anastasilakis
authors.forename: Stergios A
authors.initials: SA
authors.lastname: Polyzos
authors.forename: Athina
authors.initials: A
authors.lastname: Gkiomisi
authors.forename: Ilias
authors.initials: I
authors.lastname: Bisbinas
authors.forename: Spyridon
authors.initials: S
authors.lastname: Gerou
authors.forename: Polyzois
authors.initials: P
authors.lastname: Makras
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D024042:Collagen Type I / Q000097:blood; D000069448:Denosumab; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D017698:Postmenopause; D011347:Procollagen / Q000097:blood; D053245:RANK Ligand / Q000097:blood; D000077211:Zoledronic Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; C501126:DKK1 protein, human; D004164:Diphosphonates; D005819:Genetic Markers; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D053245:RANK Ligand; C422903:SOST protein, human; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000069448:Denosumab; D000077211:Zoledronic Acid