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

Abstract

Serum expression of microRNAs (miRs) related to bone metabolism is affected by antiosteoporotic treatment. To investigate the effect of sequential treatments on miR expression in postmenopausal women with osteoporosis. Observational, open label, nonrandomized clinical trial. A single-center outpatient clinic. 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). Relative serum expression of miRs linked to bone metabolism at 3 and 6 months of Dmab treatment. 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. 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.