Changes of Circulating MicroRNAs in Response to Treatment With Teriparatide or Denosumab in Postmenopausal Osteoporosis

J Clin Endocrinol Metab. 2018 Mar 1;103(3):1206-1213. doi: 10.1210/jc.2017-02406.

Abstract

Context: Expression of microRNAs (miRs) related to bone metabolism in the serum may be affected by antiosteoporotic treatment.

Objective: To investigate the effect of two antiosteoporotic agents with opposite effects on bone metabolism on miR expression profile in the serum.

Design: Observational, open label, nonrandomized clinical trial.

Setting: The outpatient clinics for Metabolic Bone Diseases of 424 General Military Hospital, Thessaloniki, Greece.

Patients and interventions: Postmenopausal women with low bone mass were treated with either teriparatide (TPTD; n = 30) or denosumab (n = 30) for 12 months.

Main outcome measures: Changes in the serum expression of selected miRs linked to bone metabolism at 3 and 12 months of treatment. Secondary measurements: associations of measured miRs with changes in bone mineral density (BMD) at 12 months and the bone turnover markers (BTMs) C-terminal cross-linking telopeptide of type I collagen and procollagen type I N-terminal propeptide at 3 and 12 months.

Results: We found significantly decreased relative expression of miR-33-3p at 3 months (P = 0.03) and of miR-133a at 12 months (P = 0.042) of TPTD treatment. BMD values at 12 months of TPTD treatment were significantly and inversely correlated with miR-124-3p expression at 3 months (P = 0.008). Relative expression of miR-24-3p and miR-27a was correlated with changes in BTMs during TPTD treatment and of miR-21-5p, miR-23a-3p, miR-26a-5p, miR-27a, miR-222-5p, and miR-335-5p with changes in BTMs during denosumab treatment.

Conclusions: Circulating miRs are differentially affected by treatment with TPTD and denosumab. TPTD affects the relative expression of miRs related to the expression of RUNX-2 (miR-33) and DKK-1 gene (miR-133).

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Bone Density / drug effects
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Remodeling / drug effects
  • Circulating MicroRNA / drug effects*
  • Collagen Type I / blood
  • Core Binding Factor Alpha 1 Subunit / blood
  • Denosumab / administration & dosage*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Middle Aged
  • Osteoporosis, Postmenopausal / blood
  • Osteoporosis, Postmenopausal / drug therapy*
  • Peptide Fragments / blood
  • Peptides / blood
  • Procollagen / blood
  • Teriparatide / administration & dosage*
  • Treatment Outcome

Substances

  • Biomarkers
  • Bone Density Conservation Agents
  • Circulating MicroRNA
  • Collagen Type I
  • Core Binding Factor Alpha 1 Subunit
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Peptide Fragments
  • Peptides
  • Procollagen
  • RUNX2 protein, human
  • collagen type I trimeric cross-linked peptide
  • procollagen Type I N-terminal peptide
  • Teriparatide
  • Denosumab