Serum profile of microRNAs linked to bone metabolism during sequential treatment for postmenopausal osteoporosis.

Serum expression of microRNAs (miRs) related to bone metabolism is affected by anti-osteoporotic treatment.To investigate the effect of sequential treatments on miRs expression in postmenopausal women with osteoporosis.Observational, open label, non-randomized 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 naive-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; 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; 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.

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