Zoledronic acid acutely increases sclerostin serum levels in women with postmenopausal osteoporosis

J Clin Endocrinol Metab. 2013 May;98(5):1911-5. doi: 10.1210/jc.2012-4039. Epub 2013 Apr 17.

Abstract

Context: 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.

Design and setting: We conducted a prospective intervention study in an ambulatory care setting.

Participants and intervention: 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.

Main outcomes measures: 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Aged
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Morphogenetic Proteins / blood*
  • Bone Morphogenetic Proteins / metabolism
  • Bone Regeneration / drug effects
  • Bone Resorption / etiology
  • Bone Resorption / prevention & control
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism
  • Calcium Carbonate / therapeutic use
  • Cholecalciferol / therapeutic use
  • Collagen Type I / blood
  • Collagen Type I / metabolism
  • Combined Modality Therapy
  • Dietary Supplements
  • Diphosphonates / administration & dosage
  • Diphosphonates / therapeutic use*
  • Female
  • Genetic Markers
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / therapeutic use*
  • Infusions, Intravenous
  • Middle Aged
  • Osteoporosis, Postmenopausal / blood
  • Osteoporosis, Postmenopausal / diet therapy
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / physiopathology
  • PAX5 Transcription Factor / blood
  • PAX5 Transcription Factor / metabolism
  • Peptides / blood
  • Peptides / metabolism
  • Time Factors
  • Zoledronic Acid

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Bone Density Conservation Agents
  • Bone Morphogenetic Proteins
  • Collagen Type I
  • Diphosphonates
  • Genetic Markers
  • Imidazoles
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • Peptides
  • SOST protein, human
  • collagen type I trimeric cross-linked peptide
  • Cholecalciferol
  • Zoledronic Acid
  • Calcium Carbonate