Abstract
Objective Postmenopausal women experiences osteoporotic structural damage and bone fragility resulting from reduced bone formation and increased bone resorption. Osteoporosis frequently affects the vertebral column and causes compression fractures. This study aims to characterize roles of miRNAs in osteoporosis and subsequent incidence risk of vertebral fractures for postmenopausal women. Methods. Differentially expressed miRNAs between osteoporotic patients with vertebral fractures and osteoporotic patients without fracture were identified. This retrospective study included 78 osteoporotic patients with vertebral fractures and 82 osteoporotic patients without vertebral fractures. The plasma levels of bone metabolic markers, 25-hydroxyvitamin D (25-(OH)VitD), propeptide of type I procollagen (PINP), and β-Carboxyl terminal peptide (β-CTx), were detected using the patented electro-chemiluminescence (ECLIA) method. The expression levels of miR-491-5p and miR-485-3p were determined by qRT-PCR. Pearson correlation analysis was carried out to assess the relationship between miR-491-5p, miR-485-3p, and bone metabolic markers. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to evaluate the performance of miR-491-5p and miR-485-3p in diagnosing the occurrence of vertebral fractures in osteoporotic patients.Results: The plasma levels of PINP and β-CTx were elevated but the plasma level of 25-(OH)VitD was declined in osteoporotic patients with vertebral fractures when comparable to those without (< 0.05). The plasma expression levels of miR-491-5p and miR-485-3p were declined osteoporotic patients with vertebral fractures when comparable to those without (< 0.001). Pearson correlation analysis revealed that the relative expression level of miR-491-5p was negatively correlated with the level of 25-(OH)VitD (r = -0.518, < 0.001) but positively correlated with the levels of PINP (r = 0.547, < 0.001) and β-CTx (r = 0.380, < 0.001). We also observed a negative correlation between the relative expression level of miR-485-3p and 25-(OH)VitD (r = -0.388, < 0.001), a positive correlation between miR-485-3p and PINP (r = 0.422,< 0.001). ROC curves for prediction of vertebral fracture following osteoporosis in postmenopausal women by miR-491-5p expression yielded 0.866 AUC and by miR-485-3p expression produced 0.848 AUC. Conclusion The data suggest that downregulated expressions of miR-491-5p and miR-485-3p may be involved in the occurrence of vertebral fractures in postmenopausal women with osteoporosis.
Highlights
Osteoporosis is a progressive systemic disease that is associated with bone mass decline and degradation of the bone microarchitecture, resulting in enhanced bone fragility and a greater fracture risk [1]. e incidence rate of osteoporosis increases with aging, and 30% of postmenopausal women are affected by osteoporosis in their remaining lifetime from the age of 50 years largely resulting from hormone estrogen deficiency after menopause [2]
A microarray dataset containing miRNAs profiles in osteoporotic patients with and without vertebral fractures was downloaded from the Gene Expression Omnibus, which was generated on the GPL18058 platform. e GSE93883 dataset includes a pool of 6 miRNA samples from osteoporotic patients with vertebral fractures and a pool of 6 miRNA samples from osteoporotic patients without fracture, aiming to identify differentially expressed miRNAs in plasma
After centrifugation (3000 r/min, 5 min), plasma was extracted. e lumbar and hip bone mineral density (BMD) was detected by DPX-MD dual energy X-ray bone densitometry (Luna, USA). e bone metabolism was evaluated by detecting the plasma levels of bone metabolic markers, 25⁃hydroxyvitamin D (25-(OH)VitD), propeptide of type I procollagen (PINP), and β⁃Carboxyl terminal peptide (β-CTx). e plasma levels of 25-(OH)VitD, procollagen type I N-terminal propeptide (PINP), and β-CTx were detected using the patented electrochemiluminescence (ECLIA) method by Cobas (Roche Diagnostics International Ltd., Basel, Switzerland) with a detection limit of 3 ng/ml on the Roche Elecsys 2010 Immunoassay Analyzer (Roche Diagnostics Ltd., Basel, Switzerland)
Summary
Osteoporosis is a progressive systemic disease that is associated with bone mass decline and degradation of the bone microarchitecture, resulting in enhanced bone fragility and a greater fracture risk [1]. e incidence rate of osteoporosis increases with aging, and 30% of postmenopausal women are affected by osteoporosis in their remaining lifetime from the age of 50 years largely resulting from hormone estrogen deficiency after menopause [2]. Several factors have been known to be associated with an increasing risk of fracture, especially of the spine and hip, in postmenopausal women with osteoporosis, including the history of fracture, advancing age, decreased bone mineral density (BMD), higher risk or history of falls, and certain pharmacologic therapies, such as glucocorticoids [3, 4]. With regard to women aged less than 60 years, MHT or tibolone can be suggested, especially the manifestations of vasomotor or genitourinary symptoms. In recent years, accumulating evidence has demonstrated the presence of stable cell-free mature miRNAs in blood and shows that the alternations in their serum/plasma levels can indicate both physiological and pathological states, making them useful candidate molecules as noninvasive biomarkers in osteoporosis and bone fracture risk [11]. To characterize roles of candidate miRNAs in osteoporosis and subsequent incidence risk of vertebral fractures for postmenopausal women, we chose two differentially expressed miRNAs between osteoporotic patients with vertebral fractures and osteoporotic patients without fracture, miR-491-5p and miR-485-3p, and determined their expression levels in the plasma of osteoporotic patients with vertebral fractures and osteoporotic patients without vertebral fractures
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