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

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).