title: Denosumab versus zoledronic acid in patients previously treated with zoledronic acid.
abstract: Denosumab and zoledronic acid are potent antiresorptives. In this study in patients pre-treated with zoledronic acid, denosumab achieved similar increases with zoledronic acid in lumbar spine BMD despite the more prominent reduction of bone turnover markers. Denosumab reversibly reduced endogenous RANKL.
  
  
  BACKGROUND
  We aimed to compare yearly changes in lumbar spine (LS) bone mineral density (BMD), bone turnover markers, free soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and sclerostin levels between denosumab and zoledronic acid.
  
  
  METHODS
  Postmenopausal women with low bone mass previously treated with zoledronic acid for 1 year were assigned to denosumab injection (n = 32) or zoledronic acid infusion (n = 26). Procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx), sRANKL, and sclerostin levels were measured in serum samples obtained at baseline and 3, 6, and 12 months after denosumab injection or zoledronic acid infusion. LS BMD was measured at baseline and 12 months.
  
  
  RESULTS
  The mean LS increase was 4.5 and 4.4% with denosumab and zoledronic acid, respectively (p = 0.560). Denosumab caused a larger decrease in CTx at 3 months (p < 0.001) and P1NP at 3 (p < 0.001), 6 (p = 0.021), and 12 months (p = 0.042). Denosumab significantly decreased sRANKL by 87.4% at 3 months (p < 0.001). Sclerostin levels were not changed with either intervention (p = 0.162 and p = 0.214, respectively).
  
  
  CONCLUSIONS
  In patients previously treated with zoledronic acid, denosumab reduces bone turnover more than zoledronic acid, but the increases in LS BMD are comparable. Furthermore, denosumab administration results in reversible inhibition of the metabolically significant endogenous free soluble RANKL levels. Serum sclerostin is not affected by either agent.
authors.affiliation: Department of Endocrinology, 424 General Military Hospital, Ring Road, 564 29 N.Efkarpia, Thessaloniki, Greece. anastath@endo.gr.
authors.forename: A D
authors.initials: AD
authors.lastname: Anastasilakis
authors.affiliation: Second Medical Clinic, Department of Medicine, Ippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: S A
authors.initials: SA
authors.lastname: Polyzos
authors.affiliation: Department of Obstetrics and Gynaecology, 424 General Military Hospital, Thessaloniki, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Gkiomisi
authors.affiliation: Hellenic Military School of Medicine, Thessaloniki, Greece.
authors.forename: Z G
authors.initials: ZG
authors.lastname: Saridakis
authors.affiliation: Hellenic Military School of Medicine, Thessaloniki, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Digkas
authors.affiliation: 1st Department of Orthopaedics, 424 General Military Hospital, Thessaloniki, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Bisbinas
authors.affiliation: Department of Rheumatology, 424 General Military Hospital, Thessaloniki, Greece.
authors.forename: G T
authors.initials: GT
authors.lastname: Sakellariou
authors.affiliation: Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Papatheodorou
authors.affiliation: Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Kokkoris
authors.affiliation: Department of Endocrinology and Diabetes, 251 Hellenic Air Force & VA General Hospital, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Makras
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000097:blood; D000069448:Denosumab / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D053245:RANK Ligand / Q000097:blood; D000077211:Zoledronic Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D005819:Genetic Markers; D007093:Imidazoles; D053245:RANK Ligand; C422903:SOST protein, human; C505688:TNFSF11 protein, human; D000069448:Denosumab; D000077211:Zoledronic Acid
keywords: Bone mineral density; Bone turnover markers; Denosumab; RANKL; Sclerostin; Zoledronic acid