Serum Profile of microRNAs Linked to Bone Metabolism During Sequential Treatment for Postmenopausal Osteoporosis

Abstract

Context: Serum expression of microRNAs (miRs) related to bone metabolism is affected by antiosteoporotic treatment.

Objective: To investigate the effect of sequential treatments on miR expression in postmenopausal women with osteoporosis.

Design: Observational, open label, nonrandomized clinical trial.

Setting: A single-center outpatient clinic.

Patients and interventions: Denosumab (Dmab) was administered for 12 months in 37 women who were treatment-naïve (naïve group) (n = 11) or previously treated with teriparatide (TPTD group) (n = 20) or zoledronate (ZOL group) (n = 6).

Main outcome measures: Relative serum expression of miRs linked to bone metabolism at 3 and 6 months of Dmab treatment.

Results: Baseline relative expression of miR-21a-5p, miR-23a-3p, miR-29a-3p, and miR-338-3p was higher in the TPTD group, while the relative expression of miR-21a-5p was lower in the ZOL group compared to the naïve group. Dmab decreased the relative expression of miR-21a-5p at 3 months (fold change [FC] 0.43, P < 0.001) and 6 months (FC 0.34, P < 0.001), and miR-338-3p and miR-2861 at 6 months (FC 0.31, P = 0.041; FC 0.52, P = 0.016, respectively) in the whole cohort. In subgroup analyses, Dmab decreased the relative expression of miR-21a-5p, miR-29a-3p, miR-338-3p, and miR-2861 at 3 months (FC 0.13, P < 0.001; FC 0.68, P = 0.044; FC 0.46, P = 0.012; and FC 0.16, P < 0.001, respectively) and 6 months (FC 0.1, P < 0.001; FC 0.52, P < 0.001; FC 0.04, P = 0.006; and FC 0.2, P < 0.001, respectively) only within the TPTD group.

Conclusions: TPTD treatment potentially affects the expression of the pro-osteoclastogenic miR-21a-5p and miRs related to the expression of osteoblastic genes RUNX2 (miR23a-3p), COL1 (miR-29a-3p), and HDAC5 (miR-2861), while sequential treatment with Dmab acts in the opposite direction.

Keywords: bone turnover markers; denosumab; miRNAs; osteoporosis; teriparatide; zoledronate.