Postmenopausal osteoporosis (PMOP) is a bone disorder in postmenopausal women and a significant risk factor for fragility fractures. This study aims to explore the role of miR-106a-5p in the pathogenesis of PMOP and its potential as a diagnostic biomarker.

220 postmenopausal women were recruited. The levels of miR-106a-5p, PTEN, and osteogenic-related genes were quantified using qRT-PCR. The relative protein of PTEN was detected using Western blotting. ROC curve and Pearson correlation were employed to evaluate the diagnostic value and relationships between variables. To model iron accumulation, hFOB1.19 osteoblasts were treated with ferric ammonium citrate (FAC). Cell proliferation and apoptosis were assessed using the CCK-8 and flow cytometry. The target relationship was verified using dual-luciferase assays.

miR-106a-5p levels were reduced, while PTEN levels were increased in PMOP. miR-106a-5p was positively correlated with bone mineral density and negatively correlated with ferritin. In the FAC-treated cells, miR-106a-5p decreased, and PTEN increased. Dual-luciferase assays confirmed that miR-106a-5p targets PTEN. Successful transfection was confirmed by observing the corresponding changes in miR-106a-5p and PTEN expression. Up-regulated miR-106a-5p increased the PTEN protein level, mRNA expression of RUNX2, OPN, and OCN, promoted cell proliferation, and decreased cell apoptosis under iron accumulation conditions. These effects were reversed by the upregulation of PTEN.

miR-106a-5p has the potential to diagnose osteoporosis in postmenopausal women and is linked to ferritin levels. miR-106a-5p plays a protective role in PMOP by regulating PTEN under conditions of iron accumulation, suggesting its potential as a promising biomarker for PMOP.

This study investigates age and gender differences of normative values of spleen diffusion MRI parameters.We recruited 124 volunteers with MRI conducted at 1.5T. Diffusion imaging had b-values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, 600 s/mm2. ADC, IVIM-Dslow, IVIM-PF, IVIM-Dfast, and DDVD (diffusion-derived vessel density) were computed. DDVD is the signal difference between the b=0 s/mm2 image and b=2, 4 s/mm2 image. Only images without apparent artifacts and with good curving fitting were included in the analysis. Finally, 34 females (age: 20-71 years) and 69 males (22-70 years) were measured with ADC; 20 females (20-71 years) and 48 males (22-67 years) were measured with IVIM; 32 females (20-71 years) and 65 males (22-70 years) were measured with DDVD parameter.An age-related decrease in ADC was noted for females, while such a trend was not noted for males. A very high level of heterogeneity was noted for the data for the males, with the highest ADC value being 1.710 × 10-3mm 2/s and the lowest ADC value being 0.705 × 10-3 mm2/s when b=0 and 600 s/mm 2 were used for ADC calculation. A male-female data comparison did not show a statistically significant difference between the ADC median value. However, ADCs > 1.3 × 10-3 mm2/s were only seen among males. A very high level of heterogeneity was also noted for males' Dslow, with the highest value being 1.468 × 10-3 mm2/s and the lowest value being 0.600 × 10-3 mm2/s. Both PF and Dfast demonstrated a trend of age-related increase for older subjects. PF values were higher among males than females. However, no difference was noted for Dfast between males and females. DDVD did not show an age-related trend both for females and males. No difference was noted in DDVD values between males and females.Interpreting normal spleen diffusion MRI parameters should consider age and gender factors. · An age-related decrease in spleen ADC and IVIM-Dslow was seen for healthy females.. · There is a high level of heterogeneity for spleen ADC and IVIM-Dslow data for healthy males.. · IVIM modelled perfusion fraction and Dfast demonstrate an artificial trend of age-related increase for older subjects.. · Vessel density measured on diffusion imaging does not show an age-related trend.. · Yu W, Ma FZ, Huang H et al. Age and gender differences of normative values of spleen diffusion MRI parameters. Rofo 2025; 197: 535-545.

The literature on the relationships among blood iron levels, cognitive performance, and brain iron levels specific to women at the menopausal transition is ambiguous at best. The need to better understand these potential relationships in women for whom monthly blood loss (and thus iron loss) is ceasing is highlighted by iron's accumulation in brain tissue over time, thought to be a factor in the development of neurodegenerative disease.

Non-anemic women who were either low in iron or had normal iron levels for their age and race/ethnicity provided blood samples, underwent MRI scans to estimate brain iron levels, and performed a set of cognitive tasks with concurrent EEG.

Cognitive performance and brain dynamics were positively related to iron levels, including measures associated with oxygen transport. There were no relationships between any of the blood measures of iron and brain iron.

Higher iron status was associated with better cognitive performance in a sample of women who were neither iron deficient nor anemic, without there being any indication that higher levels of systemic iron were related to higher levels of brain iron. Consequently, addressing low iron levels at the menopausal transition may be a candidate approach for alleviating the "brain fog" commonly experienced at menopause.

Excess body iron (Fe) accrual is linked to chronic diseases. East Asian (EA) adults (median age 50 y) were reported to have higher Fe stores compared to other populations despite lacking the mutation that causes Fe overload in Northern European (NE) adults. It is unknown if these differences are evident in a healthy population under 50 y of age.

This cross-sectional study aims to compare Fe-related markers in young adults of EA and NE ancestry and identify determinants of Fe status.

Participants were healthy United States males and premenopausal/nonpregnant females of genetically confirmed EA (n = 251) or NE (n = 253) ancestry, aged 18-50 y and without obesity. A complete blood count was obtained. Serum ferritin (SF; μg/L), c-reactive protein, and interleukin-6 were measured by immunoassay, and serum soluble transferrin receptor (mg/L) and transferrin by quantitative immunoturbidimetry. Total body Fe (mg/kg) was calculated. Elevated Fe stores were defined as SF >200 (females) or >300 (males) and c-reactive protein <5 mg/L. Results are shown as the geometric mean 95% confidence interval (CI) or mean ± standard deviation.

The mean age of the population was (26.3 y; 25.6, 26.9 y), with 69.2% of participants aged under 30 y. SF was higher in EA (172; 152, 194) compared with NE (85.3; 76.8, 94.8) males (P < 0.001), and in EA (42.6; 36.7, 49.5) compared with NE (31.9; 27.8, 36.5) females (P = 0.004). The prevalence of elevated Fe stores was 16.7% in EA compared with 0.8% in NE males (P < 0.001) and 1.6% in EA compared with 0% in NE females (P = 0.47). Total body Fe was higher in EA (11.7 ± 2.7) compared with NE (9.1 ± 2.6) males (P < 0.001) and in EA (6.7 ± 3.6) compared with NE (5.6 ± 3.4) females (P = 0.01). All differences persisted after adjustment for confounders (all P < 0.05).

Individuals of EA ancestry had a significantly greater body Fe burden compared to NE individuals. Of concern, these differences were evident in a cohort primarily consisting of young individuals aged 18-29 y. This trial was registered at clinicaltrials.gov as NCT04198545.

The literature on the relationships among blood iron levels, cognitive performance, and brain iron levels specific to women at the menopausal transition is ambiguous at best. The need to better to understand these potential relationships in women for whom monthly blood loss (and thus iron loss) is ceasing is highlighted by the fact that iron accumulates in brain tissue over time and that accumulation is thought to be a factor in the development of neurodegenerative disease.

Non-anemic women who were either low in iron or had normal iron levels for their age and race/ethnicity provided blood samples, underwent MRI scans to estimate brain iron levels, and performed a set of cognitive tasks with concurrent EEG. Results: Cognitive performance as well as brain dynamics were positively related to iron levels, including measures associated with oxygen transport. There were no relationships between any of the blood measures of iron and brain iron.

Higher iron status was associated with better cognitive performance in a sample of women who were neither iron deficient nor anemic, without there being any indication that higher levels of systemic iron were related to higher levels of brain. Consequently, addressing low iron levels at the menopausal transition may be a candidate approach for alleviating the "brain fog" commonly experienced at menopause.

Anemia is among the frequently observed conditions among people living with HIV (PLWH). Zidovudine (AZT) is the most common ART that causes anemia. This study aimed to identify the incidence and risk factors of AZT-induced anemia in PLWH receiving AZT-containing regimens.

A retrospective cohort study was conducted on nonpregnant PLWH aged >18 years who received AZT-containing regimens for >6 months and had normal baseline hemoglobin levels. Data on medical history, clinical characteristics, and laboratory examination were collected. Cox proportional hazard regression analysis was performed to determine the risk factors of AZT-induced anemia.

A total of 401 individuals were included in the study. In total, 71 individuals presented with AZT-induced anemia. The incidence rate of anemia was 1.98 per 100 person-years of observations. Female sex, low-normal baseline hemoglobin level, low recent and low baseline CD4 cell count were independently associated with an increased risk of anemia. However, a higher body mass index was independently associated with a decreased risk of anemia.

Routine screening, early detection, and treatment of anemia should be considered in PLWH receiving AZT-containing regimens.

Little information is available on iron with diabetes risk among African Americans, a population where both anemia and elevated ferritin are common. We tested whether plasma proteomic measurements of ferritin and transferrin were associated with increased diabetes risk in a cohort of current and former African American (NHB) and Non-Hispanic White (NHW) smokers.

NHB and NHW participants from the COPDGene study who were free of diabetes (n = 4693) at baseline were followed for incident diabetes. The SomaScan was used to determine the relative amounts of natural log-transformed ferritin, transferrin, and hepcidin.

During an average of 5.6 years of follow-up, diabetes incidence was 7.9%. Ferritin at follow-up was higher in NHB than NHW participants (p = <0.0001). Ferritin at follow-up was associated with increased diabetes risk (OR = 1.36, 95% CI = 1.08-1.70), while transferrin was associated with decreased risk (OR = 0.25, 95% CI = 0.08-0.77) controlling for age, sex, BMI, smoking pack-years, hepcidin, CRP, and Il-6. Race-specifically, increased risk associated with higher ferritin levels among NHB (OR = 1.56, 95% CI = 1.13-2.16) but not NHW (OR = 1.22, 95% CI = 0.89-1.68) participants. Sex-specifically, ferritin's relationship was similar among NHB men and women and NHW women (ORs ranging from 1.41-1.59); but not NHW men (OR = 0.98, 95% CI = 0.64-1.49). Similarly, transferrin ORs non-significantly ranged from 0.19-0.30 for NHB men and women and NHW women, but was significant for NHW men (OR = 0.07, 95% CI = 0.01-0.63).

Higher body iron stores is associated with increased diabetes risk among both NHB and NHW people. Unsuspected elevated iron stores may increase diabetes risk in NHB patients and should be monitored.

This study investigated the effects of quercetin on the alterations of serum elements in perimenopausal depression rat model induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS) and possible mechanisms. According to the results of the sucrose preference test, the rats were randomly assigned to four groups: sham, OVX-CUMS, OVX-CUMS + 17β-estradiol (17β-estradiol: 0.27 mg/kg.bw), and OVX-CUMS + Quercetin (Quercetin: 50 mg/kg.bw). At the end of experiment, serum and prefrontal cortex of rats were collected. The inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that levels of calcium (Ca), magnesium (Mg), selenium (Se), cobalt (Co) and zinc (Zn) decreased, and levels of iron (Fe) and copper (Cu) increased in serum and prefrontal cortex of OVX-CUMS rats compared with sham group (p < 0.01). Meanwhile, the levels of the above elements in prefrontal cortex had correlation with behavioral characteristics in OVX-CUMS rats (p < 0.05 or p < 0.01). The abnormal elements in serum may cross blood-brain-barrier into the brain and induce oxidative stress, leading to ferroptosis. Furtherly, the expressions of ferroptosis-related protein including GPX4 and SLC7A11 were decreased in prefrontal cortex of OVX-CUMS rats (p < 0.01), which confirmed the above results. Quercetin treatment restored the above abnormal indicators (p < 0.05 or p < 0.01) induced by OVX-CUMS in rats. Our study suggested that quercetin regulated variation of elements in serum and prefrontal cortex, further inhibiting ferroptosis in prefrontal cortex through alleviating oxidative stress in OVX-CUMS rats.

Despite the high incidence of dry mouth in postmenopausal women, its underlying mechanisms and therapeutic interventions remain underexplored. Using ovariectomized (OVX) mouse models, here this study identifies ferroptosis, an iron-dependent regulated cell death, as a central mechanism driving postmenopausal salivary gland (SG) dysfunction. In the OVX-SGs, TGFβ signaling pathway is enhanced with the aberrant TGFβ2 expression in SG mesenchymal cells. Intriguingly, TGFβ2 treatment reduces iron-storing ferritin levels, leading to lipid peroxidation and ferroptotic death in SG epithelial organoids (SGOs). Mechanistically, TGFβ2 promotes the autophagy-mediated ferritin degradation, so-called ferritinophagy. A notable overexpression of the type III TGFβ receptor (TβRIII) is found in the OVX-SGs and TGFβ2-treated SGOs, while the silencing of TβRIII mitigates the ferroptosis-mediated deleterious effects of TGFβ2 on SGOs. Finally, administration of ferroptosis inhibitor, Liproxstatin-1 (Lip-1), improves saliva secretion in OVX mice. Present findings collectively suggest a link between TGFβ signaling, ferroptosis, and SG injury, offering new therapeutic avenues for postmenopausal xerostomia.

T1 mapping of the liver is confounded by the presence of fat. Multiparametric T1 mapping combines fat-water separation with T1-weighting to enable imaging of water-specific T1 (T1Water), proton density fat fraction (PDFF), and T2* values. However, normative T1Water values in the liver and its dependence on age/sex is unknown.

Determine normative values for T1Water in the liver with comparison to MOLLI and evaluate a T2*-compensation approach to reduce T1 variability.

Prospective observational; phantoms.

One hundred twenty-four controls (56 male, 18-75 years), 50 patients at-risk for liver disease (18 male, 30-76 years).

2.89 T; Saturation-recovery chemical-shift encoded T1 Mapping (SR-CSE); MOLLI.

SR-CSE provided T1Water measurements, PDFF and T2* values in the liver across three slices in 6 seconds. These were compared with MOLLI T1 values. A new T2*-compensation approach to reduce T1 variability was evaluated test/re-test reproducibility.

Linear regression, ANCOVA, t-test, Bland and Altman, intraclass correlation coefficient (ICC). P < 0.05 was considered statistically significant.

Liver T1 values were significantly higher in healthy females (F) than males (M) for both SR-CSE (F-973 ± 78 msec, M-930 ± 72 msec) and MOLLI (F-802 ± 55 msec, M-759 ± 69 msec). T1 values were negatively correlated with age, with similar sex- and age-dependencies observed in T2*. The T2*-compensation model reduced the variability of T1 values by half and removed sex- and age-differences (SR-CSE: F-946 ± 36 msec, M-941 ± 43 msec; MOLLI: F-775 ± 35 msec, M-770 ± 35 msec). At-risk participants had elevated PDFF and T1 values, which became more distinct from the healthy cohort after T2*-compensation. MOLLI systematically underestimated liver T1 values by ~170 msec with an additional positive T1-bias from fat content (~11 msec/1% in PDFF). Reproducibility ICC values were ≥0.96 for all parameters.

Liver T1Water values were lower in males and decreased with age, as observed for SR-CSE and MOLLI acquisitions. MOLLI underestimated liver T1 with an additional large positive fat-modulated T1 bias. T2*-compensation removed sex- and age-dependence in liver T1, reduced the range of healthy values and increased T1 group differences between healthy and at-risk groups.

2 TECHNICAL EFFICACY: Stage 1.

A balanced and healthy diet during the menopausal transition and after menopause is crucial for women to reduce the risk for morbidities and chronic diseases due to deficiency of essential nutrients.

The objective of this study was to conduct a systematic review of studies that analyzed the impact of vitamin and nutrient deficiencies in postmenopausal women in relation to increased morbidities and chronic conditions.

Observational studies were searched in the databases PubMed, UpToDate, and Google Scholar.

We searched 122 studies, of which 90 were included in our analysis. The meta-analysis of the data could not be performed because of the heterogeneity of the statistical methods in the included studies. In our study, we focused on the aspects of vitamin B6, vitamin B12, vitamin D, iron, omega-3-fatty acids, and lycopene, belonging to the family of carotenoids. Postmenopausal women with deficiencies of these nutrients are more vulnerable to comorbidities such as cardiovascular and cerebrovascular events, metabolic diseases, osteoporosis, obesity, cancer and neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, depression, cognitive decline, dementia, and stroke. We concluded that women after menopause tend to have a greater probability of suffering from deficiencies in various vitamins and nutrients, and consequently have an increased risk of developing morbidities and chronic diseases.

In conclusion, maintaining optimum serum levels of nutrients and vitamins, either through a balanced and healthy diet consuming fresh fruits, vegetables, and fats or by taking appropriate supplementation, is essential in maintaining optimal health-related quality of life and reducing the risk for women during the menopausal transition and after menopause. Nevertheless, more recent studies need to be assessed to formulate adequate recommendations to achieve positive clinical outcomes.

The current study investigated the correlation between dietary iron intake and diabetic kidney disease among diabetic adults.

This cross-sectional study enrolled 8118 participants who suffered from diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Dietary iron intake was obtained from 24 h recall interviews, and diabetic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or albumin creatinine ratio (ACR) ≥ 30 mg/g. Three weighted logistic regression models were utilized to investigate odd ratio (OR) and 95% CIs for diabetic kidney disease. Stratified analyses were performed by gender, age, BMI, HbA1c, hypertension status, and smoking status, and diabetes types.

Among 8118 participants (51.6% male, mean age 61.3 years), 40.7% of participants suffered from diabetic kidney disease. With the adjustment of potential covariates, we found that ≥ 12.59 mg of dietary iron was related to a lower risk of diabetic kidney disease (OR = 0.78, 95% CI: 0.63 to 0.96; OR = 0.79, 95% CI: 0.63 to 0.98). In stratified analyses, higher iron intake was negatively related to diabetic kidney disease, especially among those who were male, < 60 years, those with hypertension, those with HbA1c < 7.0%, and those who were ex-smokers. The result remained robust in sensitivity analyses.

We found that ≥ 12.59 mg of dietary iron is associated with a lower risk of diabetic kidney disease, especially in those who were male, younger, heavier weight, have better blood sugar control, and those who were ex-smokers.

The prevalence of iron deficiency varies widely according to how it is defined.

To compare the prevalence of iron deficiency among women using 3 different definitions.

The cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS; 2000-2006) evaluated the prevalence, determinants, and outcomes of hemochromatosis and other iron-related disorders. Multiethnic, primary care-based screening (2001-2003) was performed at 5 field centers (4 in the US and 1 in Canada). Volunteer women aged 25 years and older were recruited at primary care venues associated with the field centers. Data were analyzed from June to December 2023.

Measures included transferrin saturation, serum ferritin level, and self-reported age, pregnancy, and race and ethnicity. Three iron deficiency definitions were studied: (1) combined transferrin saturation less than 10% and serum ferritin less than 15 ng/mL (HEIRS), (2) serum ferritin less than 15 ng/mL (World Health Organization [WHO]), and (3) serum ferritin less than 25 ng/mL (a threshold for iron-deficient erythropoiesis [IDE]).

Among 62 685 women (mean [SD] age, 49.58 [14.27] years), 1957 women (3.12%) had iron deficiency according to the HEIRS definition, 4659 women (7.43%) had iron deficiency according to the WHO definition, and 9611 women (15.33%) had iron deficiency according to the IDE definition. Among 40 381 women aged 25 to 54 years, 1801 women (4.46%) had iron deficiency according to HEIRS, 4267 women (10.57%) had iron deficiency according to WHO, and 8573 women (21.23%) had iron deficiency according to IDE. Prevalence rates of iron deficiency among 2039 women aged 25 to 44 years who reported pregnancy were 5.44% (111 women) according to HEIRS, 18.05% (368 women) according to WHO, and 36.10% (736 women) according to IDE. Iron deficiency prevalence by the 3 respective definitions increased significantly in each racial and ethnic group and was significantly higher among Black and Hispanic participants than Asian and White participants. The relative iron deficiency prevalence among the 62 685 women increased 2.4-fold (95% CI, 2.3-2.5; P < .001) using the WHO definition and increased 4.9-fold (95% CI, 4.7-5.2; P < .001) using the IDE definition.

Three definitions of iron deficiency were associated with significantly different prevalence of iron deficiency in women, regardless of self-reported age, pregnancy, or race and ethnicity. Using higher serum ferritin thresholds to define iron deficiency could lead to diagnosis and treatment of more women with iron deficiency and greater reduction of related morbidity.

Biological hormonal changes are frequently cited as an explanatory factor of sex and menopause differences in cardiometabolic diseases (CMD) and its associated risk factors. However, iron metabolism which varies between sexes and among women of different reproductive stages could also play a role. Recent evidence suggest that iron may contribute to CMD risk by modulating oxidative stress pathways and inflammatory responses, offering insights into the mechanistic interplay between iron and CMD development. In the current review, we provide a critical appraisal of the existing evidence on sex and menopausal differences in CMD, discuss the pitfall of current estrogen hypothesis as sole explanation, and the emerging role of iron in CMD as complementary pathway. Prior to menopause, body iron stores are lower in females as compared to males, but the increase during and after menopause, is tandem with an increased CMD risk. Importantly, basic science experiments show that an increased iron status is related to the development of type 2 diabetes (T2D), and different cardiovascular diseases (CVD). While epidemiological studies have consistently reported associations between heme iron intake and some iron biomarkers such as ferritin and transferrin saturation with the risk of T2D, the evidence regarding their connection to CVD remains controversial. We delve into the factors contributing to this inconsistency, and the limitation of relying on observational evidence, as it does not necessarily imply causation. In conclusion, we provide recommendations for future studies on evaluating the potential role of iron in elucidating the sex and menopausal differences observed in CMD.

To examine the association of iron biomarkers with menopausal status and assess whether these biomarkers can help differentiate menopausal status beyond age.

In this cross-sectional study we included 1679 women from the CoLaus and 2133 from the PREVEND cohorts, with CoLaus used as primary cohort and PREVEND for replication. Ferritin, transferrin, iron, and transferrin saturation (TSAT) were used to assess iron status. Hepcidin and soluble transferrin receptor were assessed only in PREVEND. Menopausal status was self-reported and defined as menopausal or non-menopausal. Logistic regressions were used to explore the association of these iron biomarkers with menopause status. Sensitivity, specificity, area under the receiver operating characteristic curves (AUC), positive and negative predictive values as well as cut-off points for the iron biomarkers were calculated. The model with the highest AUC was defined as the best.

In the CoLaus and PREVEND cohorts, respectively, 513 (30.6 %) and 988 (46.3 %) women were postmenopausal. Ferritin (OR, 2.20; 95 % CI 1.72-2.90), transferrin (OR, 0.03; 95 % CI 0.01-0.10), and TSAT (OR, 1.28; 95 % CI 1.06-1.54) were significantly associated with menopausal status in CoLaus, with the findings replicated in PREVEND. AUC of age alone was 0.971. The best model resulted from combining age, ferritin, and transferrin, with an AUC of 0.976, and sensitivity and specificity of 87.1 % and 96.5 %, respectively. Adding transferrin and ferritin to a model with age improved menopause classification by up to 7.5 %. In PREVEND, a model with age and hepcidin outperformed a model with age, ferritin, and transferrin.

Iron biomarkers were consistently associated with menopausal status in both cohorts, and modestly improved a model with age alone for differentiating menopause status. Our findings on hepcidin need replication.

This study aimed to investigate the association between blood trace elements and bone mineral density (BMD) and to determine the association between blood trace elements and the risk of low BMD/osteoporosis among US adults.

We performed a cross-sectional study using data from National Health and Nutrition Examination Survey (NHANES, 2011-2016). Multivariable linear regression models were employed to assess the associations of BMD in lumbar spine (LS-BMD), pelvic (PV-BMD) and total femur (TF-BMD) with blood trace elements, including Fe, Zn, Cu, Se, Mn, Cd, Pb, Hg. Additionally, the associations of low BMD/osteoporosis with blood trace elements were also evaluated using multivariable logistic regression.

Higher blood Pb levels were found associated with decreased LS-BMD (p for trend < 0.001), PV-BMD (p for trend = 0.007), and TF-BMD (p for trend = 0.003) in female, while higher blood Se levels were associated with increased PV-BMD in female (p for trend = 0.042); no linear association between BMD and other blood trace element was observed. Also, significant associations were found between Pb levels and the prevalence of low BMD (p for trend = 0.030) and the prevalence of osteoporosis (p for trend = 0.036), while association between other blood trace elements and low BMD/osteoporosis was not observed.

This study provides comprehensive insight into the association between blood trace elements and BMD and supports a detrimental effect of blood Pb levels on bone mass in women. Considering our analysis from a representative US general population, further study is warranted for the extreme levels of blood trace elements on bone metabolism.

Either H2S or iron is essential for cellular processes. Abnormal metabolism of H2S and iron has increased risk for cardiovascular diseases. The aim of the present study is to examine the mutual interplay of iron and H2S signals in regulation of vascular smooth muscle cell (SMC) functions. Here we found that deficiency of cystathionine gamma-lyase (CSE, a major H2S-producing enzyme in vascular system) induced but NaHS (a H2S donor) administration attenuated iron accumulation in aortic tissues from angiotensin II-infused mice. In vitro, iron overload induced labile iron levels, promoted cell proliferation, disrupted F-actin filaments, and inhibited protein expressions of SMC-specific markers (αSMA and calponin) more significantly in SMCs from CSE knockout mice (KO-SMCs) than the cells from wild-type mice (WT-SMCs), which could be reversed by exogenously applied NaHS. In contrast, KO-SMCs were more vulnerable to iron starvation-induced cell death. Either iron overload or NaHS did not affect elastin level and gelatinolytic activity. We further found that H2S induced more aconitase activity of iron regulatory protein 1 (IRP1) but inhibited its RNA binding activity accompanied with increased protein levels of ferritin and ferriportin, which would contribute to the lower level of labile iron level inside the cells. In addition, iron was able to suppress CSE-derived H2S generation, while iron also non-enzymatically induced H2S release from cysteine. This study reveals the mutual interaction between iron and H2S signals in regulating SMC phenotypes and functions; CSE/H2S system would be a target for preventing iron metabolic disorder-related vascular diseases.

The importance of serum ferritin has been demonstrated in many liver diseases, but its relationship with liver stiffness remains unclear. The objective of this study was to investigate the association between serum ferritin levels and participants' liver stiffness measurement (LSM) in the United States population. We conducted a screening of participants from National Health and Nutrition Examination Survey (NHANES) 2017.1 to 2020.3 to ensure that participants included in this study had complete serum ferritin and LSM information. Association between the independent variable (serum ferritin) and the dependent variable (LSM) was investigated by multiple linear regression and subgroup analysis was performed to identify sensitive individuals, and we subsequently assessed whether there was a non-linear relationship between the 2 using smoothed curve fitting and threshold effect models. The final 7143 participants were included in this study. There was a positive association between participants' serum ferritin concentration and LSM, with an effect value of (β = 0.0007, 95% confidence interval (CI): 0.0002-0.0011) in the all-adjusted model. The smoothing curve and threshold effect models indicated a non-linear positive correlation between serum ferritin and LSM, which was more pronounced when serum ferritin concentration exceeded 440 ng/mL. Subsequent subgroup analysis showed that this positive correlation was more pronounced in males (β = 0.0007, 95% CI: 0.0001-0.0012), age >60 years (β = 0.00015, 95% CI: 0.0007-0.0023), black participants (β = 0.00018, 95% CI: 0.0009-0.0026), and participants with body mass index (BMI) <25 kg/m2 (β = 0.00012, 95% CI: 0.0005-0.0020). In U.S. adults, there was a positive correlation between serum ferritin levels and liver stiffness, which was more pronounced when serum ferritin exceeded 440 ng/mL. Our study suggested that regular serum ferritin testing would be beneficial in monitoring changes in liver stiffness. Male, age >60 years, black participants, and those with a BMI < 25 kg/m2 should be of greater consideration.

The risk of chronic diseases increases markedly with age and after menopause. An increase in bodily iron following menopause could contribute to this phenomenon of increased risk of chronic diseases. We aimed to investigate how various iron biomarkers change with advancing age, according to sex and menopausal status.

We enrolled community-dwelling individuals with available information on ferritin, transferrin, iron, hepcidin, and soluble transferrin receptor levels from the Prevention of Renal and Vascular Endstage Disease study. The association of the iron biomarkers with age, sex, and menopausal status was investigated with linear regression models.

Mean (SD) age of the 5222 individuals (2680 women [51.3%], among whom 907 [33.8%] were premenopausal, 529 [19.7%] perimenopausal, and 785 [29.3%] postmenopausal), was 53.4 (12.0) years. Iron biomarkers showed a constant increase in women throughout their life course, in some cases at older ages surpassing values in men who, in turn, showed consistently higher levels of iron status compared to women in most age categories. Ferritin, hepcidin, and transferrin saturation levels were 3.03, 2.92, and 1.08-fold (all p < 0.001) higher in postmenopausal women compared to premenopausal.

We found that iron accumulates differently depending on sex, age, and menopausal status. An increased iron status was identified in women, especially during and after menopause.

Osteoporosis is prevalent in postmenopausal women. The underlying reason is mainly estrogen deficiency, but recent studies have indicated that osteoporosis is also associated with iron accumulation after menopause. It has been confirmed that some methods of decreasing iron accumulation can improve the abnormal bone metabolism associated with postmenopausal osteoporosis. However, the mechanism of iron accumulation-induced osteoporosis is still unclear. Iron accumulation may inhibit the canonical Wnt/β-catenin pathway via oxidative stress, leading to osteoporosis by decreasing bone formation and increasing bone resorption via the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa-B ligand (RANKL)/receptor activator of nuclear factor kappa-B (RANK) system. In addition to oxidative stress, iron accumulation also has been reported to inhibit either osteoblastogenesis or osteoblastic function as well as to stimulate either osteoclastogenesis or osteoclastic function directly. Furthermore, serum ferritin has been widely used for the prediction of bone status, and nontraumatic measurement of iron content by magnetic resonance imaging may be a promising early indicator of postmenopausal osteoporosis.

The sex difference in alcohol use disorder (AUD) is ingrained in distinctive neurobiological responses between men and women, which necessitates further investigation for a more tailored management.

Minding the findings of iron dysregulation in AUD and the sex difference in iron homeostasis in multiple physiological and pathological settings, we examined the sex difference in the association between serum ferritin and blood alcohol concentration (BAC) in intoxicated males (n = 125) and females (n = 59). We included patients with both serum ferritin tested of any value and a BAC above the level of detection during the same hospital admission period. We investigated sex difference in the relationship between BAC, serum ferritin and liver enzymes in intoxicated critically ill and noncritically ill patients.

We found a negative association between serum ferritin and BAC in critically ill, intoxicated females [R2 = 0.44, F(1,14) = 11.02, p = 0.005], with much attenuated serum ferritin in females compared to their male counterparts (194.5 ± 280.4 vs. 806.3 ± 3405.7 ng/L, p = 0.002). We found a positive association between serum ferritin and liver enzymes [alanine transaminase (ALT) and aspartate transferase (AST)] in critically ill intoxicated females [ALT: R2 = 0.48, F(1,10) = 9.1, p = 0.013; AST: R2 = 0.68, F(1,10) = 21.2, p = 0.001] and in noncritically ill intoxicated males [ALT: R2 = 0.1, F(1,83) = 9.4, p = 0.003; AST: R2 = 0.1, F(1,78) = 10.5, p = 0.002]. The effect of BAC on serum ferritin was not mediated by ALT [indirect effect: (B = 0.13, p = 0.1)]. We also found a significant effect of sex, anemia, intensive care unit (ICU) admission and mortality on serum ferritin.

Our results suggest that high BAC in intoxicated female patients is associated with attenuated serum ferritin levels, questioning the role of low serum ferritin in female vulnerability to alcohol.

We appraised the relationship between the biological and the chronological age and estimated the rate of biological aging in HIV-infected patients. Two independent biomarkers, the relative telomere length and iron metabolism parameters, were analyzed in younger (<35) and older (>50) HIV-infected and uninfected patients (control group). In our control group, telomeres of younger patients were significantly longer than telomeres of older ones. However, in HIV-infected participants, the difference in the length of telomeres was lost. By combining the length of telomeres with serum iron, ferritin, and transferrin iron-binding capacity, a new formula for determination of the aging process was developed. The life expectancy of the healthy population was related to their biological age, and HIV-infected patients were biologically older. The effect of antiretroviral HIV drug therapies varied with respect to the biological aging process. IMPORTANCE This article is focused on the dynamics of human aging. Moreover, its interdisciplinary approach is applicable to various systems that are aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant.

Iron is essential to organisms, the liver plays a vital role in its storage. Under pathological conditions, iron uptake by the intestine or hepatocytes increases, allowing excess iron to accumulate in liver cells. When the expression of hepcidin is abnormal, iron homeostasis in humans cannot be regulated, and resulting in iron overload. Hepcidin also regulates the release of iron from siderophores, thereby regulating the concentration of iron in plasma. Important factors related to hepcidin and systemic iron homeostasis include plasma iron concentration, body iron storage, infection, inflammation, and erythropoietin. This review summarizes the mechanism and regulation of iron overload caused by hepcidin, as well as related liver diseases caused by iron overload and treatment.

Elevated concentrations of ferritin seem to be detrimental to human health while being quite common in the elderly. Data on dietary, anthropometric, and metabolic correlates of circulating ferritin levels in the elderly are scant.

We aimed to identify a dietary pattern, anthropometric, and metabolic traits associated with plasma ferritin status in an elderly cohort (n = 460, 57% male, age: 66 ± 12 y) from Northern Germany.

Plasma ferritin levels were measured by immunoturbidimetry. Reduced rank regression (RRR) yielded a dietary pattern explaining 13% of the variation in circulating ferritin concentrations. Cross-sectional associations of anthropometric and metabolic traits with plasma ferritin concentrations were assessed using multivariable-adjusted linear regression analysis. Restricted cubic spline regression was used to identify nonlinear associations.

The RRR pattern was characterized by a high intake of potatoes, certain vegetables, beef, pork, processed meat, fats (frying and animal fat), and beer and a low intake of snacks, representing elements of the traditional German diet. BMI, waist circumference, and CRP were directly, HDL cholesterol inversely, and age nonlinearly associated with plasma ferritin concentrations (all P < 0.05). After additional adjustment for CRP, only the association of ferritin with age remained statistically significant.

Higher plasma ferritin concentrations were associated with a traditional German dietary pattern. The associations of ferritin with unfavorable anthropometric traits and low HDL cholesterol were rendered statistically nonsignificant upon additional adjustment for chronic systemic inflammation (CRP), suggesting that these associations were largely driven by the proinflammatory role of ferritin (an acute-phase reactant). J Nutr 20xx;x:xx.

Iron deficiency and overload may negatively impact women's health. There has been limited assessment of iron status and its associated factors among Canadian women.

This study investigated associations of various sociodemographic, lifestyle, medication, and dietary factors with body iron stores among pre- and postmenopausal women in Canada.

Analyses were conducted using cross-sectional, nationally representative survey and biomarker data from women aged 20-79 y (n = 6362) in the Canadian Health Measures Survey (2009-2017). Body iron stores were assessed by measuring serum concentrations of ferritin (SF). Information on potential correlates was collected during an in-home interview. Multivariable linear regression analyses were performed to evaluate associations with SF concentration, and logistic regression was used to estimate associations with iron deficiency (SF <15 μg/L) or elevated iron stores (SF >150 μg/L).

Geometric mean SF concentrations were significantly higher in postmenopausal than in premenopausal women (73.2 versus 33.8 μg/L; P < 0.001). The prevalence of iron deficiency among pre- and postmenopausal women was 16.0% and 4.0%, respectively, whereas that of elevated iron stores was 2.7% and 21.0%, respectively. After simultaneous adjustment for multiple factors, including high-sensitivity CRP (inflammation marker), we found that age, East/Southeast Asian (versus White) race/ethnicity, alcohol, and red meat consumption were positively associated with SF concentration among pre- and postmenopausal women. In addition, aspirin use and dairy consumption were inversely associated with SF concentration among postmenopausal women only. Similar patterns were observed for associations with elevated iron stores among postmenopausal women, whereas higher grain consumption was associated with an increased prevalence of iron deficiency among premenopausal women.

Sociodemographic, lifestyle, medication, and dietary factors are correlated with iron status determined by SF concentration among Canadian women. The findings may have implications for intervention strategies aimed at optimizing body iron stores in pre- and postmenopausal women.

This study measured serum markers of iron status in naturally menstruating and oral contraceptive (OC) athletes during the main hormonal milieus of these two profiles to identify potential differences confounding the diagnosis of iron deficiency in female athletes. Resting blood samples were collected from 36 naturally menstruating athletes during the early-follicular phase (EFP), mid- late-follicular phase (MLFP) and mid-luteal phase (MLP) of the menstrual cycle. Simultaneously, blood samples were collected from 24 OC athletes during the withdrawal and active-pill phase of the OC cycle. Serum iron, ferritin, transferrin, transferrin saturation (TSAT), C-reactive protein (CRP), interleukin-6 and sex hormones were analyzed. Naturally menstruating athletes showed lower levels of TSAT, iron and transferrin than OC athletes when comparing the bleeding phase of both profiles (p<0.05) as well as when comparing all analyzed phases of the menstrual cycle to the active pill phase of the OC cycle (p<0.05). Interestingly, only lower transferrin was found during MLFP and MLP compared to the withdrawal phase of the OC cycle (p>0.05), with all other iron markers showing no differences (p>0.05). Intracycle variations were also found within both types of cycle, presenting reduced TSAT and iron during menstrual bleeding phases (p<0.05). In conclusion, in OC athletes, serum iron availability, but not serum ferritin, seems higher than in naturally menstruating ones. However, such differences are lost when comparing the MLFP and MLP of the menstrual cycle with the withdrawal phase of the OC cycle. This should be considered in the assessment of iron status in female athletes.Highlights Naturally menstruating athletes present lower TSAT, iron and transferrin in all analyzed phases of the menstrual cycle compared to OC athletes during their active pill phase. However, both the mid-late follicular and mid-luteal phases of the menstrual cycle do not differ from the withdrawal phase of the oral contraceptive cycle.Intracycle variations are found for TSAT and iron in both naturally menstruating and oral contraceptive athletes, which are mainly driven by a reduction in TSAT and iron during menstrual bleeding phases.As serum iron availability changes significantly as a function of the athlete's hormonal status, it should be considered in the assessment of the athlete's iron status as well as standardise the phase of the menstrual cycle in which to assess iron markers to avoid misdiagnosis or misleading results.In contrast, the assessment of iron stores through serum ferritin is substantially stable and the athlete's hormonal status does not seem to be of relevance for this purpose.

Osteoporosis is a common metabolic bone disease that results from the imbalance of homeostasis within the bone. Intra-bone homeostasis is dependent on a precise dynamic balance between bone resorption by osteoclasts and bone formation by mesenchymal lineage osteoblasts, which comprises a series of complex and highly standardized steps. Programmed cell death (PCD) (e.g., apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis) is a cell death process that involves a cascade of gene expression events with tight structures. These events play a certain role in regulating bone metabolism by determining the fate of bone cells. Moreover, existing research has suggested that natural products derived from a wide variety of dietary components and medicinal plants modulate the PCDs based on different mechanisms, which show great potential for the prevention and treatment of osteoporosis, thus revealing the emergence of more acceptable complementary and alternative drugs with lower costs, fewer side effects and more long-term application. Accordingly, this review summarizes the common types of PCDs in the field of osteoporosis. Moreover, from the perspective of targeting PCDs, this review also discussed the roles of currently reported natural products in the treatment of osteoporosis and the involved mechanisms. Based on this, this review provides more insights into new molecular mechanisms of osteoporosis and provides a reference for developing more natural anti-osteoporosis drugs in the future.

Levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), a marker of heart failure and cardiovascular risk, are generally higher in women than men. We explored whether iron biomarkers mediate sex differences in NT-proBNP levels.

We included 5,343 community-dwelling individuals from the Prevention of Renal and Vascular Endstage Disease study. With linear regression analyses, we investigated the association of sex and iron biomarkers with NT-proBNP levels, independent of adjustment for potential confounders. The assessed iron biomarkers included ferritin, transferrin saturation (TSAT), hepcidin, and soluble transferrin receptor (sTfR). Next, we performed mediation analyses to investigate to which extent iron biomarkers influence the association between sex and NT-proBNP.

Of the included 5,343 participants, the mean standard deviation age was 52.2 ± 11.6 years and 52% were females. After adjustment for potential confounders, women compared to men, had higher NT-proBNP (β = 0.31; 95%CI = 0.29, 0.34), but lower ferritin (β = -0.37; 95%CI = -0.39, -0.35), hepcidin (β = -0.22, 95%CI = -0.24, -0.20), and TSAT (β = -0.07, 95% CI = -0.08, -0.06). Lower ferritin (β = -0.05, 95%CI = -0.08, -0.02), lower hepcidin (β = -0.04, 95%CI = -0.07, -0.006), and higher TSAT (β = 0.07; 95%CI = 0.01, 0.13) were associated with higher NT-proBNP. In mediation analyses, ferritin and hepcidin explained 6.5 and 3.1% of the association between sex and NT-proBNP, respectively, while TSAT minimally suppressed (1.9%) this association.

Our findings suggest that iron biomarkers marginally explain sex differences in levels of NT-proBNP. Future studies are needed to explore causality and potential mechanisms underlying these pathways.

In this review, we discuss the effects on androgens on the haemopoietic system, focussing largely on the effects of testosterone on erythropoiesis. Stimulation of erythropoiesis is one of the most consistent effects of testosterone treatment observed in clinical trials. In men with anaemia this effect can be beneficial. Conversely, erythrocytosis is one of the most common adverse effects of testosterone treatment with a relative risk of 8.14 (95% CI: 1.87-35.40) estimated by a recent meta-analysis of randomised placebo controlled clinical trials. A reduction in haemoglobin is commonly seen in men receiving androgen deprivation therapy for prostate cancer, and in transwomen receiving gender affirming therapy to reduce serum testosterone. While mechanisms by which androgens regulate erythropoiesis are not fully understood, it is likely that effects on erythropoietic progenitor cells and erythropoietin are involved, with secondary effects on iron metabolism. In contrast, whether androgens exert clinically relevant effects on white blood cells and on platelets requires further study.

Aim: To identify the relationship between ferritin and outcomes for patients with hip fractures. Patients & methods: All patients with hip fractures presenting between May 2017 and January 2021 were included. Univariate and multivariate analyses were performed to determine the risk factors for 1-year survival. Propensity score matching (PSM) was performed for groups divided by ferritin levels. Results: A total of 165 patients were included of whom 28 died during the first year after surgery. Ferritin levels differed significantly between groups divided by 1-year survival. High ferritin (≥308.5 ng/ml) was related to poor 1-year survival and 6-month and 1-year independent walking rate. Conclusion: High ferritin (≥308.5 ng/ml) may predict poor survival and free-walking abilities after surgery for patients with hip fractures.

There are multiple diseases or conditions such as hereditary hemochromatosis, hemophilia, thalassemia, sickle cell disease, aging, and estrogen deficiency that can cause iron overload in the human body. These diseases or conditions are frequently associated with osteoarthritic phenotypes, such as progressive cartilage degradation, alterations in the microarchitecture and biomechanics of the subchondral bone, persistent joint inflammation, proliferative synovitis, and synovial pannus. Growing evidences suggest that the conditions of pathological iron overload are associated with these osteoarthritic phenotypes. Osteoarthritis (OA) is an important complication in patients suffering from iron overload-related diseases and conditions. This review aims to summarize the findings and observations made in the field of iron overload-related OA while conducting clinical and basic research works. OA is a whole-joint disease that affects the articular cartilage lining surfaces of bones, subchondral bones, and synovial tissues in the joint cavity. Chondrocytes, osteoclasts, osteoblasts, and synovial-derived cells are involved in the disease. In this review, we will elucidate the cellular and molecular mechanisms associated with iron overload and the negative influence that iron overload has on joint homeostasis. The promising value of interrupting the pathologic effects of iron overload is also well discussed for the development of improved therapeutics that can be used in the field of OA.