Analysis and Validation of Hub Genes in Blood Monocytes of Postmenopausal Osteoporosis Patients

Osteoporosis is a common systemic bone disease caused by the imbalance between osteogenic activity and osteoclastic activity. Aged women are at higher risk of osteoporosis, partly because of estrogen deficiency. However, the underlying mechanism of how estrogen deficiency affects osteoclast activity has not yet been well elucidated. In this study, GSE2208 and GSE56815 datasets were downloaded from GEO database with 25 PreH BMD women and 25 PostL BMD women in total. The RRA algorithm determined 38 downregulated DEGs and 30 upregulated DEGs. Through GO analysis, we found that downregulated DEGs were mainly enriched in myeloid cell differentiation, cytokine-related functions while upregulated DEGs enriched in immune-related biological processes; pathways like Notch signaling and MAPK activation were found in KEGG/Rectome pathway database; a PPI network which contains 66 nodes and 91 edges was constructed and three Modules were obtained by Mcode; Correlation analysis helped us to find highly correlated genes in each module. Moreover, three hub genes FOS, PTPN6, and CTSD were captured by Cytohubba. Finally, the hub genes were further confirmed in blood monocytes of ovariectomy (OVX) rats by real-time PCR assay. In conclusion, the integrative bioinformatics analysis and real-time PCR analysis were utilized to offer fresh light into the role of monocytes in premenopausal osteoporosis and identified FOS, PTPN6, and CTSD as potential biomarkers for postmenopausal osteoporosis.

Non-hormonal options for the relief of menopausal disorders

Woman’s nature is unique. Taking into account some historical milestones, it can be noted that the role of women in society has undergone large-scale changes. The woman took a confident position in society. Its main function remains unchanged and it consists in procreation and procreation. A woman’s activity is consistent with the work of her reproductive system (RS). The gradual decrease, and then the cessation of the work of the ovaries, contributes to the life order and health of the fair sex. Menopause is a natural stage in a woman’s life, which corresponds to the peak of social self-realization. However, in some cases, hormonal changes characteristic of this period can serve as a favorable background for the formation of a number of pathological changes. The growing estrogen deficiency is becoming a pathogenetic impetus for the development of a wide range of climacteric disorders. Vasomotor symptoms and hyperhidrosis are the most frequent companions of women during the perimenopausal transition and early postmenopause. Maintaining optimal activity and the full quality of life of patients should be the goal of correcting the negative manifestations of estrogen deficiency and the complications associated with it. Compensating for estrogen deficiency with menopausal hormone therapy (HRT) is the benchmark for menopausal problems. However, there are a number of patients who have contraindications to prescribing HRT or who refuse to receive it for some reason. For this category of patients, alternative methods of diet correction. Combinations of plant extracts with vitamins and minerals have been successfully used in clinical practice for a long time. The article will provide information on the most studied phytoestrogens contained in soy.

Ibandronate Suppresses Changes in Apatite Orientation and Young's Modulus Caused by Estrogen Deficiency in Rat Vertebrae

Bone material quality is important for evaluating the mechanical integrity of diseased and/or medically treated bones. However, compared to the knowledge accumulated regarding changes in bone mass, our understanding of the quality of bone material is lacking. In this study, we clarified the changes in bone material quality mainly characterized by the preferential orientation of the apatite c-axis associated with estrogen deficiency-induced osteoporosis, and their prevention using ibandronate (IBN), a nitrogen-containing bisphosphonate. IBN effectively prevented bone loss and degradation of whole bone strength in a dose-dependent manner. The estrogen-deficient condition abnormally increased the degree of apatite orientation along the craniocaudal axis in which principal stress is applied; IBN at higher doses played a role in maintaining the normal orientation of apatite but not at lower doses. The bone size-independent Young's modulus along the craniocaudal axis of the anterior cortical shell of the vertebra showed a significant and positive correlation with apatite orientation; therefore, the craniocaudal Young’s modulus abnormally increased under estrogen-deficient conditions, despite a significant decrease in volumetric bone mineral density. However, the abnormal increase in craniocaudal Young's modulus did not compensate for the degradation of whole bone mechanical properties due to the bone loss. In conclusion, it was clarified that changes in the material quality, which are hidden in bone mass evaluation, occur with estrogen deficiency-induced osteoporosis and IBN treatment. Here, IBN was shown to be a beneficial drug that suppresses abnormal changes in bone mechanical integrity caused by estrogen deficiency at both the whole bone and material levels.

Oral cavity status in menopausal and postmenopausal women

The purpose of this review was to analyze and summarize the available literature data on changes of oral tissues in menopausal/postmenopausal women. We searched for the relevant references in Pubmed database using appropriate key words. We had revealed about 3,500 references on these topics and analyzed the most relevant. Postmenopausal women have an increased risk of the decrease of bone mineral density due to estrogen deficiency. Estrogens induce osteoclast apoptosis and intensity of this protective mechanism decreases after the cessation of menstruation. Most cross-sectional radiographic studies have confirmed an association between age-related osteoporosis and decreased alveolar bone height. It has been established that postmenopausal women with generalized chronic periodontitis are characterized by severe destruction of the periodontium, which progresses in parallel to a decrease in bone mineral density. Sex hormones maintaining bone integrity and strength, involved in regulating the proliferation, differentiation, and growth of keratinocytes and fibroblasts of the gums. The effect of low estrogen levels on keratinization of the gum epithelium and decreased salivation can lead to menopausal gingivostomatitis. Estrogen deficiency also adversely affects the microenvironment of gingival sulcus, including the composition and circulation of crevicular fluid. Postmenopausal women have lower salivary pH and lower salivation, which is associated with deterioration of periodontal tissues. In addition, the postmenopausal period is characterized by the changes in the microbial composition of the oral cavity, IgG decreases in the crevicular fluid and prooxidant changes of saliva. Conclusions. The oral cavity status in menopausal and postmenopausal women undergoes significant changes: a decrease in bone mineral density, dryness of mucous membranes, microbiome changes, and activation of oxidative and immune processes. These changes necessitate regular examinations, timely treatment and application of all measures of preventive dentistry. There is also a need for randomized clinical trials and create standardized guidelines for the management of postmenopausal patients with periodontal disease.

A patient with Turner syndrome received the percutaneous vertebroplasty seven times: a case report and literature review

Background Turner syndrome (TS) is characterized as the complete or partial absence of one X chromosome and is an extremely rare disease affecting approximately 1:2500 live female births. Though the prevalence of osteoporosis among women with TS is estimated to be around 55–64% and they suffer more frequently from fractures than normal, few reports concerning TS patients with osteoporosis are able to be seen due to tiny number of patients. Case presentation Here, we report a rare case of TS with osteoporosis, who has undergone percutaneous vertebroplasty (PVP) seven times because of several vertebral compression fractures (VCFs). G-banded karyotype analysis was performed and the result was 45,X[43]/47,XXX[17], indicating that the patient was a mosaicism of TS karyotype and Trisomy X syndrome karyotype. TS is the underlying cause of low level of estrogen for this patient. The interaction of aging, estrogen deficiency and intestinal dysbacteriosis leads to her severe osteoporosis and multi-segmental VCFs. The aim of this report is to provide recommendations regarding the management of TS patients with osteoporosis by reviewing the clinical presentation of TS, the influence of estrogen deficiency in osteoporosis, etc. Conclusions Early diagnosis and hormone replacement treatment are essential for TS patients to prevent osteoporosis and reduce the risk of fractures. This is a rare case report describing TS patient with severe osteoporosis and VCFs.

Global phosphoproteomic profiling of skeletal muscle in ovarian hormone-deficient female mice

Dynapenia, the age-related loss of skeletal muscle strength without the loss of muscle mass, significantly impacts the activities and quality of life of the aging population. Studies have shown that dynapenia occurs earlier in females than males in both human and rodent studies. Moreover, in females, estrogen deficiency has been shown to contribute to the loss of skeletal muscle strength as well as blunted recovery of strength after injury. The maintenance of skeletal muscle contractile function is vital to the overall health of women, especially as women live 1/3 of their life in an estrogen deficient state. Reversible protein phosphorylation is an indispensable post-translational modification, playing a key role in signal transduction pathways. Phosphorylation of skeletal muscle proteins have been shown to regulate sarcomeric function, excitation-contraction coupling, energy metabolism, and fiber-type composition. To define the physiological changes in the skeletal muscle phosphoproteome associated with estrogen deficiency, we used an ovariectomy model coupled with mass spectrometry. We identified, in total, 5,424 unique phosphorylation sites and 1,177 phosphoproteins in the tibialis anterior muscle. Ingenuity Pathway Analysis show decreased phosphorylation of contractile proteins and significant predicted inhibition of the upstream kinase, CDK6 (z-score -2.0) in ovariectomized compared to control muscles. Our results suggest that estrogen deficiency remodels the skeletal muscle phosphoproteome which may alter phosphorylation signaling that might contribute to the loss of strength in females.

Rhizoma drynariae total flavonoids combined with calcium carbonate ameliorates bone loss in experimentally induced Osteoporosis in rats via the regulation of Wnt3a/β-catenin pathway

Background Rhizoma drynariae, a traditional Chinese herb, is commonly used in treatment of bone healing in osteoporotic fractures. However, whether the Rhizoma drynariae total flavonoids (RDTF) can promote the absorption of calcium and enhance the bone formation is unclear. The aim of the present study was to investigate the preventive effects of RDTF combined with calcium carbonate (CaCO3) on estrogen deficiency-induced bone loss. Methods Three-month-old Sprague–Dawley rats were ovariectomized (OVX) and then treated with CaCO3, RDTF, and their admixtures for ten weeks, respectively. The bone trabecular microstructure, bone histopathological examination, and serum biomarkers of bone formation and resorption were determined in the rat femur tissue. The contents of osteoprotegerin (OPG), receptor activator of the NF-κB (RANK), and its ligand (RANKL) in marrow were analyzed by ELISA, and the protein expressions of Wnt3a, β-catenin, and phosphorylated β-catenin (p-β-catenin) were analyzed by Western blot. Statistical analysis was conducted by using one-way analysis of variance (ANOVA) followed by LSD post hoc analysis or independent samples t test using the scientific statistic software SPSS version 20.0 Results RDTF combined with CaCO3 could promote osteosis and ameliorate bone loss to improve the repair of cracked bone trabeculae of OVX rats. Furthermore, RDTF combined with CaCO3 also could prevent OVX-induced decrease in collagen fibers in the femoral tissue of ovariectomized rats and promote the regeneration of new bone or cartilage tissue, while CaCO3 supplementation promoted the increase in bone mineral content. Nevertheless, there was no difference in the expression of Wnt3a, β-catenin and p-β-catenin between osteopenic rats and RDTF treated rats, but RDTF combined with CaCO3 could activate the Wnt3a/β-catenin pathway. Conclusions RDTF combined with CaCO3 could ameliorate estrogen deficiency-induced bone loss via the regulation of Wnt3a/β-catenin pathway.

Serum interleukin-17 and estradiol levels in postmenopausal women in relation to osteoporosis

Background In post-menopausal women, estrogen deficiency leads to instability between bone formation and resorption which is regulated by osteoclastogenic cytokines leading to resorption. Interleukin-17 (IL-17) a proinflammatory cytokine has been found as an important regulator of osteoclast-genesis induced by estrogen deficiency in favor of bone loss in animal studies. The study aimed to evaluate levels of IL-17 and estrogen (E2) in relation to bone mineral density (BMD) and risk of fracture in postmenopausal women with and without osteoporosis. Results IL-17 levels were significantly higher and E2 levels were significantly lower in the osteoporotic group compared to the non-osteoporotic group (P value ≤ 0.01). There was a highly significant difference in DEXA score and FRAX index between two groups: with higher values of FRAX and lower values of DEXA score among osteoporotic group (P value ≤ 0.01). IL-17 was inversely correlated to estrogen level and highly significant negative correlation with DEXA as well as a highly significant positive one with FRAX index. IL-17 serum level was able to diagnose osteoporosis at a cutoff level of > 80 pg/mL with 100% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 100% negative predictive value (NPV). Conclusions Serum IL-17 was significantly elevated in osteoporotic postmenopausal women when compared to healthy postmenopausal ones and was inversely correlated with estrogen level and DEXA.