Assessment Association of Dietary Inflammatory Index and Circulating micro-RNAs (miR-21, miR-422a, miR-503) in Postmenopausal Women with and without Primary Osteoporosis

Abstract

Abstract Background: Considering the role of inflammation in the pathogenesis of osteoporosis in postmenopausal women, dietary inflammatory index (DII) score is important in the development or prevention of osteoporosis in postmenopausal women. microRNAs have been considered as promising candidates for the diagnosis of osteoporosis in postmenopausal women. Dietary parameters may alter inflammation by increasing or decreasing microRNAs, so this study aimed to determine and compare DII and circulating microRNAs (miR-21, miR-422a, and miR-503) and their relationship together in women with and without primary osteoporosis. Materials & Methods: This analytical cross-sectional study was performed on eligible postmenopausal women aged 50-65 years in Tabriz. After checking the inclusion-exclusion criteria, venous blood samples were taken from 536 postmenopausal women in the fasting state in order to exclude individuals with secondary osteoporosis and to assess the plasma level of microRNAs. Diagnosis of osteoporosis evaluated by dual-energy X-ray absorptiometry method, 232 postmenopausal women consisted 124 women with normal bone mineral density (normal-BMD) were selected as the control group and 108 women with osteoporosis were selected as the case group. DII was calculated based on a food frequency questionnaire. Individual plasma samples were evaluated for expression levels of miR-21, miR-422a, and miR-503 using RT-PCR. After data collection, Mann-Whitney test was used to compare DII and independent t-test was used to compare microRNA in the two groups. A Linear regression test was used to investigate the relationship between DII and microRNAs. Also, logistic regression test for comparison of continuous and modeled DII according to the middle of the control group DII, and comparison continuous and modeled miRNA based on the middle of the control group miRNA with osteoporosis used in the two groups. Results: The median (maximum and minimum) DII in the normal group was -0.31 (2.70 and -3.71) and in the osteoporosis group was 0.97 (4.16 and -1.27). The expression level of all three microRNAs was significantly higher in the osteoporosis group than normal (P <0.001). There was a positive and significant relationship between DII and the expression level of miR-422 (P <0.06) and miR-503 (P <0.09) expression in all postmenopausal women, but this relationship was not significant in normal and osteoporosis groups.The odds of getting osteoporosis 2.394 with one unit increase of DII. It also in women with DII higher than the median of the control group was significantly higher than the other group (ORDII >-0.31 /≤-0.31=3.15, 95% CI: 1.419-7.013, p-value=0.005). The probability of developing osteoporosis in postmenopausal women with expression levels of miR-21, miR-422a, and miR-503 lower than the median of the control group was 99.3%, 98.0, and 99.9% lower than the women with upper than the median of the control group, respectively. Conclusion: Postmenopausal women with a pro-inflammatory diet (with a higher DII), and higher plasma levels of miR-21, miR-422, and miR-503; are more likely to develop osteoporosis. Also, with increasing DII, the expression of miR-21 and miR-422 increases in postmenopausal women with and without osteoporosis. But DII in normal density postmenopausal women and osteoporosis were not associated with the studied microRNAs. Keywords: DII, osteoporosis, menopause, miR-21, miR-422a and miR-503