title: Zoledronic acid acutely increases sclerostin serum levels in women with postmenopausal osteoporosis.
abstract: BACKGROUND
  Sclerostin is a circulating inhibitor of the Wnt-signaling pathway produced by osteocytes, which acts as a negative regulator of bone formation. Effects of zoledronic acid on sclerostin serum levels in postmenopausal osteoporosis are unknown.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate sclerostin serum levels after zoledronic acid administration and correlate variations with bone turnover markers.
  
  
  METHODS
  We conducted a prospective intervention study in an ambulatory care setting.
  
  
  METHODS
  Forty women (mean age 62.6 ± 4.9 years) with postmenopausal osteoporosis were enrolled in this study and randomized into 2 groups to receive zoledronic acid (5 mg) or placebo.
  
  
  METHODS
  At baseline and then at 2, 7, 30, and 360 days after zoledronic acid or placebo administration, serum levels of sclerostin, bone-specific alkaline phosphatase (BSAP), as a bone formation marker, and serum C-telopeptide of type 1 collagen (CTX), as a bone resorption marker, were measured.
  
  
  RESULTS
  Sclerostin serum levels increased by day 2, reached a peak at day 7 (3-fold baseline, P < .001), and then decreased at day 30 and returned near to baseline after 360 days in the zoledronic acid group. Both CTX and BSAP were reduced, and a significant negative correlation was observed between the percentage changes of sclerostin and the variation in BSAP and CTX at all time points in the zoledronic acid group (P < .05). No changes were observed in the placebo group.
  
  
  CONCLUSIONS
  Our data demonstrate that zoledronic acid increases sclerostin serum levels and that sclerostin could play a role in coupling bone resorption to bone formation.
authors.affiliation: Department of Internal Medicine, University of Messina, 98125 Messina, Italy. catalanoantonino@libero.it
authors.forename: Antonino
authors.initials: A
authors.lastname: Catalano
authors.forename: Nancy
authors.initials: N
authors.lastname: Morabito
authors.forename: Giorgio
authors.initials: G
authors.lastname: Basile
authors.forename: Santa
authors.initials: S
authors.lastname: Brancatelli
authors.forename: Domenico
authors.initials: D
authors.lastname: Cucinotta
authors.forename: Antonino
authors.initials: A
authors.lastname: Lasco
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000097:blood* / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002119:Calcium Carbonate / Q000627:therapeutic use; D002762:Cholecalciferol / Q000627:therapeutic use; D024042:Collagen Type I / Q000097:blood / Q000378:metabolism; D003131:Combined Modality Therapy; D019587:Dietary Supplements; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy* / Q000503:physiopathology; D051757:PAX5 Transcription Factor / Q000097:blood / Q000378:metabolism; D010455:Peptides / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D000077211:Zoledronic Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D004164:Diphosphonates; D005819:Genetic Markers; D007093:Imidazoles; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D010455:Peptides; C422903:SOST protein, human; C052929:collagen type I trimeric cross-linked peptide; D002762:Cholecalciferol; D000077211:Zoledronic Acid; D002119:Calcium Carbonate