Menopausal Transition: Prospective Study of Estrogen Status, Circulating MicroRNAs, and Biomarkers of Bone Metabolism

Abstract

ObjectiveOsteoporosis is associated with an impaired balance between bone resorption and formation, which in turn leads to bone loss and fractures. Many recent studies have underlined the regulatory role of microRNAs (miRNAs) in bone remodeling processes and their potential as biomarkers of osteoporosis. The purpose of this study was to prospectively examine the association of circulating miRNAs and bone biomarkers with estrogen status in women before and after oophorectomy, as well as in oophorectomized women on estrogen therapy.MethodsIn this prospective study, we included 11 women before oophorectomy and hysterectomy and at 201 ± 24 days after the surgery. Another 11 women were evaluated 508 ± 127 days after oophorectomy and hysterectomy and after an additional 203 ± 71 days of estradiol treatment. Serum miRNAs were profiled by sequencing. Estrogen status and biomarkers of bone metabolism were quantified. Bone mineral density was assessed in the lumbar spine.ResultsOur analysis revealed 17 miRNAs associated with estrogen levels. Of those miRNAs that were upregulated with estrogen deficiency and downregulated after estrogen therapy, miR-422a correlated with serum beta-carboxy-terminal type I collagen crosslinks (β-CTX) and procollagen 1 N-terminal propeptide (P1NP); and miR-1278 correlated with serum β-CTX, P1NP, osteocalcin, sclerostin, and Dickkopf-1(Dkk1). In contrast, we found an inverse association of miR-24-1-5p with estrogen status and a negative correlation with serum β-CTX, P1NP, osteoprotegerin, and sclerostin levels.ConclusionThe reported miRNAs associated with estrogen status and bone metabolism could be potential biomarkers of bone pathophysiology and would facilitate studies on the prevention of postmenopausal osteoporosis. Our findings require validation in an extended cohort.

Circulating miR-340-5p and miR-506-3p as Two Osteo-miRNAs for Predicting Osteoporosis in a Cohort of Postmenopausal Women

“…Considering excellent stability, tissue specificity, as well as easy detection of circulating miRNAs, they have been widely applied for the prediction and early diagnosis of human diseases, including metabolic bone disease [ 16 ]. miRNAs are shown to be closely associated with osteoblast and osteoclast differentiation and survival in the context of bone formation [ 17 ]. We performed differential expression analysis using miRNA expression profiles of the GSE201543 dataset and found the top 5 upregulated circulating miRNAs ranked by p values in osteoporotic postmenopausal women compared with postmenopausal women with normal BMD, miR-4527, miR-5186, miR-340-5p, miR-506-3p, and miR-4770.…”

Bone protection mechanism of Zuogui Pill in an osteoporosis model of breast cancer rats after endocrine therapy

“…The ovarian function decl ine after menopause is caused by a sharp decline in oestrogen levels, as well as AI treatment of breast cancer caused by oestrogen synthesis disorders; the combination of these two factors results in low levels of oestrogen, and the decrease of oestrogen level reduces OB activity, increases OC activity, and destroys its dynamic balance. These changes promote bone loss and lead to osteoporo sis (OP) [20][21][22][23][24].…”

Pivotal Role of Intestinal Microbiota and Intraluminal Metabolites for the Maintenance of Gut–Bone Physiology

“…Another hormone that contributes to the growth and maturation of bones is estrogen. This steroid hormone regulates mammalian reproduction bone turnover in adult bones and promotes the proper closure of the epiphyseal growth plates during bone growth [ 50 ]. Decreased estrogen production in postmenopausal women is an underlying factor in the rapid bone resorption, resulting in osteoporosis, that many women experience [ 51 , 52 ].…”