No genetic causal association between circulating alpha-tocopherol levels and osteoarthritis, a two-sample Mendelian randomization analysis.

The causal association between vitamin E status and osteoarthritis (OA) remains controversial in previous epidemiological studies. We employed a Mendelian randomization (MR) analysis to explore the causal relationship between circulating alpha-tocopherol levels (main forms of vitamin E in our body) and OA. The instrumental variables (IVs) of circulating alpha-tocopherol levels were obtained from a Genome-wide association study (GWAS) dataset of 7781 individuals of European descent. The outcome of OA was derived from the UK biobank. Two-sample MR analysis was used to estimate the causal relationship between circulating alpha-tocopherol levels and OA. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic in this work. The heterogeneity effect of instrumental IVs was detected by MR-Egger and IVW analyses. Sensitivity analysis was performed by removing single nucleotide polymorphism (SNP) one by one. Three SNPs (rs964184, rs2108622, and rs11057830) (P < 5E-8) strongly associated with circulating alpha-tocopherol levels were used in this analysis. The IVW-random effect indicated no causal relationship between circulating alpha-tocopherol levels and clinically diagnosed OA (OR = 0.880, 95% CI 0.626, 1.236, P = 0.461). Similarly, IVW analysis showed no causal association between circulating alpha-tocopherol levels and self-reported OA (OR = 0.980, 95% CI 0.954, 1.006, P = 0.139). Other methods of MR analyses and sensitivity analyses revealed consistent findings. MR-Egger and IVW methods indicated no significant heterogeneity between IVs. The MR-Egger intercept showed no horizontal pleiotropic. The results of this linear Mendelian randomization study indicate no causal association between genetically predicted alpha-tocopherol levels and the progression of OA. Alpha-tocopherol may not provide beneficial and more favorable outcomes for the progression of OA. Further MR analysis based on updated GWASs with more IVs is required to verify the results of our study.

Associations Between Serum Selenium and Bone Mineral Density in 8-19-year-old children and adolescents: NHANES 2013-2018.

The peak bone mass (PBM) in puberty has been proven to be a critical determinant of osteoporosis and brittle fractures in the elderly. Selenium is an essential trace element that could influence bone metabolism in our bodies. However, no study has investigated the impact of selenium status on bone mineral density (BMD) among children and adolescents. This was a cross-section study from National Health and Nutrition Examination Survey (NHANES) in the USA involving participants aged 8-19 years. We conducted multiple linear regression models to assess the relationship between selenium status and BMD among children and adolescents, and then stratified analyses were performed according to genders and races. Smooth curve fits and two-piecewise linear regression models were conducted to explore their nonlinear relationship. A total of 4570 participants (2338 boys and 2232 girls) were included in the present study, with a mean age of 13.57 ± 3.41 years. In the multivariable adjustment model, serum selenium was positively associated with lumbar spine BMD (ß = 0.021 95% CI: 0.008, 0.034, P = 0.001). The dose-response analyses indicated a non-linear inverted U-shaped relationship between serum selenium and lumbar spine BMD. Lower and higher selenium concentrations were related to decreased BMD, and the inflection point of serum selenium was 2.60 umol/L. The inverted U-shaped association was also observed in females (inflection point: 2.49 umol/L), males (inflection point: 2.65 umol/L), Non-Hispanic White (inflection point: 2.50 umol/L), Non-Hispanic Black (inflection point: 2.50 umol/L), and other races (Including multi-racial) (inflection point: 2.81 umol/L). Our study first shows a non-linear inversed U-shaped association between selenium status and BMD among children and adolescents. The proper selenium status will benefit bone health in children and adolescents. More research is still required to verify our findings and their potential mechanisms.

Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study.

Introduction: The causal association between non-alcoholic fatty liver disease (NAFLD) and osteoporosis remains controversial in previous epidemiological studies. We employed a bidirectional two-sample Mendelian analysis to explore the causal relationship between NAFLD and osteoporosis. Method: The NAFLD instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Two-sample Mendelian randomization (MR) analyses were used to estimate the causal effect of NAFLD on osteoporosis, fracture, and fall. Reverse Mendelian randomization analysis was conducted to estimate the causal effect of osteoporosis on NAFLD. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic. The heterogeneity effect of IVs was detected by MR-Egger and IVW analyses. Results: Five SNPs (rs2980854, rs429358, rs1040196, rs738409, and rs5764430) were chosen as IVs for NAFLD. In forward MR analysis, the IVW-random effect indicated the causal effect of NAFLD on osteoporosis (OR= 1.0021, 95% CI: 1.0006-1.0037, P= 0.007) but not on fracture (OR= 1.0016, 95% CI: 0.998-1.0053, P= 0.389) and fall (OR= 0.9912, 95% CI: 0.9412-1.0440, P= 0.740). Furthermore, the reverse Mendelian randomization did not support a causal effect of osteoporosis on NAFLD (OR= 1.0002, 95% CI: 0.9997-1.0007, P= 0.231). No horizontal pleiotropic was detected in all MR analyses. Conclusions: The results of this study indicate a causal association between NAFLD and osteoporosis. NAFLD patients have a higher risk of osteoporosis but not fracture and falling risk. In addition, our results do not support a causal effect of osteoporosis on NAFLD.

Association between caffeine consumption and bone mineral density in children and adolescent: Observational and Mendelian randomization study.

BACKGROUND: Coffee is the most commonly consumed beverage among children and adolescences. Caffeine was demonstrated to be associated with bone metabolism. However, the relationship between caffeine intake and BMD in children and adolescents remains unclear. This study aimed to identified relationship between caffeine consumption and bone mineral density (BMD) in children and adolescents. METHODS: Based on National Health and Nutrition Examination Survey (NHANES), we conducted an epidemiological cross-section study to measure the relationship between caffeine consumption and BMD in children and adolescents by multivariate linear regression models. Then, five methods of Mendelian randomization (MR) analyses were performed to estimate their causal relationship between coffee and caffeine intake and BMD in children and adolescents. MR-Egger and inverse-variance weighted (IVW) were used to evaluate the heterogeneity effect of instrumental variables (IVs). RESULTS: In epidemiological studies, individuals with the highest quartile of caffeine intake do not have a significant change in femur neck BMD (ß = 0.0016, 95% CI: -0.0096, 0.0129, P = 0.7747), total femur BMD (ß = 0.0019, P = 0.7552), and total spine BMD (ß = 0.0081, P = 0.1945) compared with the lowest quartile. In MR analysis, the IVW-random effect indicates no causal relationship between coffee consumption and TB- BMD (ß = 0.0034, P = 0.0910). Other methods of MR analyses and sensitivity analysis reveals consistent findings. Similarly, the fixed-effects IVW method shows no causal association between caffeine intake and TB-BMD in children and adolescents (ß = 0.0202, P = 0.7828). CONCLUSIONS: Our study does not support a causal relationship between caffeine consumption and BMD in children and adolescents. However, more studies are needed to verify our findings, such as its underlying molecular mechanisms and the long-term impact of early caffeine exposure at a younger age.

Global and regional prevalence of vitamin D deficiency in population-based studies from 2000 to 2022: A pooled analysis of 7.9 million participants.

Background: Vitamin D deficiency causes the bone hypomineralization disorder osteomalacia in humans and is associated with many non-skeletal disorders. We aim to estimate the global and regional prevalence of vitamin D deficiency in people aged 1 year or older from 2000 to 2022. Methods: We systematically searched Web of Science, PubMed (MEDLINE), Embase, Scopus, and Google databases on December 31, 2021, and updated them on August 20, 2022, without language and time restrictions. Meanwhile, we identified references of relevant system reviews and eligible articles and included the latest and unpublished data from the National Health and Nutrition Examination Survey (NHANES, 2015-2016 and 2017-2018) database. The studies investigating the prevalence of vitamin D deficiency in population-based studies were included. A standardized data extraction form was used to collect information from eligible studies. We used a random-effects meta-analysis to estimate the global and regional prevalence of vitamin D deficiency. We stratified meta-analyses by latitude, season, six WHO regions, the World Bank income groups, gender, and age groups. This study was registered with PROSPERO (CRD42021292586). Findings: Out of 67,340 records searched, 308 studies with 7,947,359 participants from 81 countries were eligible for this study, 202 (7,634,261 participants), 284 (1,475,339 participants), and 165 (561,978 participants) studies for the prevalence of serum 25(OH)D <30, <50, and <75 nmol/L, respectively. We found that globally, 15.7% (95% CrI 13.7-17.8), 47.9% (95% CrI 44.9-50.9), and 76·6% (95% CrI 74.0-79.1) of participants had serum 25-hydroxyvitamin D levels less than 30, 50, and 75 nmol/l, respectively; the prevalence slightly decreased from 2000-2010 to 2011-2022, but it was still at a high level; people living in high latitude areas had a higher prevalence; the prevalence in winter-spring was 1.7 (95% CrI 1.4-2.0) times that in summer-autumn; the Eastern Mediterranean region and Lower-middle-income countries had a higher prevalence; females were vulnerable to vitamin D deficiency; gender, sampling frame, detection assays, sampling region, time of data collection, season, and other factors contributed to heterogeneity between the included studies. Interpretation: Globally, vitamin D deficiency remained prevalent from 2000 to 2022. The high prevalence of vitamin D deficiency would increase the global burden of disease. Therefore, governments, policymakers, health workers, and individuals should attach importance to the high prevalence of vitamin D deficiency and take its prevention as a public health priority. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021292586, PROSPERO CRD42021292586.

Associations between vitamin E status and bone mineral density in children and adolescents aged 8-19 years: Evidence based on NHANES 2005-2006, 2017-2018.

INTRODUCTION: Bone mineral density (BMD) in adolescence is a crucial determinant in osteoporosis and fragility fractures in older age. Vitamin E is the most abundant lipid-soluble antioxidant present in the blood. However, the association of vitamin E status with BMD in children and adolescents remains unclear. METHODS: We first measured the association of vitamin E status (serum α- and γ tocopherol) with BMD in children and adolescents with the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression models were performed to evaluate their relationship after adjusting for a large range of covariates. Stratified analyses and interaction tests were used to explore their effects on different genders, ages, and races/ethnicities. RESULTS: 13,606 children and adolescents from NHANES (2005-2006, 2017-2018) were included in our analysis. Compared with the lowest α-tocopherol quartile, individuals in the highest α-tocopherol quartile are likelier to be Non-Hispanic White and have a higher value of poverty income ratio (PIR). They have a lower value of serum phosphorus and lumbar spine BMD. Every 1umol/L increase in serum α- and γ- tocopherol, the lumbar spine BMD decreased by -0.0016 and -0.0068 g/cm2. Compared with the lowest quartile serum α- and γ- tocopherol concentration, individuals in the highest quartile have a -0.0223 and -0.0329 g/cm2 lower mean BMD, respectively. Interaction effects suggest that the negative effect is more prominent among female youth, individuals aged 8-13 years, non-Hispanic whites, Mexican Americans, and non-Hispanic blacks. CONCLUSIONS: Our study indicates serum α- and γ-tocopherol are negatively correlated with lumbar BMD. Age, gender, and race may have a modifying effect on this relationship. Our study has an important clinical implication. A higher vitamin E status for children and adolescents could not improve BMD, even decrease BMD. More prospective research with stronger evidence is needed to verify our findings and their underlying mechanisms.

Prevalence, trend, and predictor analyses of vitamin D deficiency in the US population, 2001-2018.

Background: The National Health and Nutrition Examination Surveys (NHANES) collect and release data to the public every 2 years. The latest NHANES study on the vitamin D status of Americans was based on data from 2001 to 2014, and the latest data (2015-2016 and 2017-2018) have not been studied yet. Thus, we extracted all the available data from NHANES (2001-2018), aiming to analyze the prevalence and trends of vitamin D deficiency (VDD) in the US population to bridge the research gap. Methods: According to previous studies and nutritional guidelines for vitamin D, severe VDD was defined as serum 25(OH)D levels of <25 nmol/L, moderate deficiency as 25-50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75 nmol/L. We comprehensively estimated the prevalence of serum 25(OH)D levels of <25, 25-50, 50-75, and >75 nmol/L in Americans and described trends in vitamin D status from 2001 to 2018. Weighted multivariate linear regression models were used to explore the predictors of VDD. All analyses and the data were adjusted for the complex sampling design of NHANES using Mobile Examination Center (MEC) weights. Results: Based on the most recent data of 71,685 participants, our study showed that the weighted prevalence of severe and moderate VDD was 2.6% and 22.0%, and the prevalence of vitamin D insufficiency (VDI) and sufficiency was 40.9% and 34.5%. The prevalence of severe and moderate VDD was higher in women, non-Hispanic black Americans, people aged 20-29 years, and during the season of winter. From 2001 to 2018, we found a slight linear decrease in the prevalence of moderate VDD (coefficient = -0.847; P = 0.009) and VDI (coefficient = -0.810; P = 0.014). We also found a slight linear increase in vitamin D sufficient (coefficient = 1.693; P = 0.004). However, no trend change was observed in severe VDD (coefficient = -0.037; P = 0.698). Age, sex, ethnicity, season, sun-protective behaviors, lower BMI, lower socioeconomic status (SES), drinking, and lower milk consumption were predictors of severe VDD. Conclusion: Vitamin D deficiency is still prevalent in the United States, especially in non-Hispanic black Americans, women, individuals aged 20-29, and during winter. Therefore, individuals, healthcare providers, and policymakers should take public health measures to develop and implement prevention strategies to deal with VDD.

Blood Lead Level Is Negatively Associated With Bone Mineral Density in U.S. Children and Adolescents Aged 8-19 Years.

Context: The relationship of lead (Pb) exposure with bone health in children and adolescents remains controversial. Objection: We aimed to investigate the association of blood lead levels (BLL) with bone mineral density (BMD) in American children and adolescents using data from the National Health and Nutrition Examination Survey (NHANES), 2005-2010. Methods: We analyzed 5,583 subjects aged 8-19 years (mean age, 13.49 ± 3.35 years) from the NHANES 2005-2010. BLL was tested using inductively coupled plasma mass spectrometry. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, total femur, and femur neck. Multivariate linear regression models were used to explore the association between BLL and BMD, adjusting for age, gender, race/ethnicity, poverty income ratio (PIR), body mass index (BMI), serum calcium, and serum phosphorus. Results: BLL was negatively correlated with BMD at different sites of interest in children and adolescents. For every 1mg/dl increase in BLL, the BMD of the total spine, total hip, and femoral neck decreased by 0.011 g/cm2, 0.008 g/cm2, and 0.006 g/cm2. In addition, Pb affected the lumbar spine more than the femur. The effect estimates were stronger in girls than boys at the lumbar spine (P for interaction= 0.006). This negative association remained significant in American children and adolescents after excluding individuals with BLL more than 3.5 ug/dl. Conclusion: Our study indicates that BLL is negatively correlated with BMD at different sites of interest in children and adolescents aged 8-19 years, even in the reference range. More research is needed to elucidate the relationships between Pb and bone health in children and adolescents, including specific mechanisms and confounding factors like race/ethnicity, gender, and age.

Socioeconomic status influences on bone mineral density in American men: findings from NHANES 2011-2020.

The association between socioeconomic status (SES) and bone mineral density (BMD) in men remains controversial. We showed that SES was positively associated with BMD in American men. Confounding factors like race/ethnicity and age could affect the association. INTRODUCTION: Based on the data from the National Health and Nutrition Examination Survey (NHANES), 2011-2020, this article aims to investigate the association of SES (poverty income ratio (PIR) and education level) with the BMD in American men. METHODS: We evaluated the association of SES with BMD in 4446 men aged ≥ 20 years (mean age, 41.0 ± 13.4 years) from the NHANES 2011-2020. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine. We used multivariate linear regression models to examine the relationship between SES and total spine BMD, adjusted for a large range of confounding factors. RESULTS: Compared with other PIR quarters, individuals in the highest quarter of PIR were more likely to be older and white and had fewer smoking or drinking behaviors. After adjusting for race/ethnicity, age, drinking and smoking behavior, body mass index (BMI), total protein, serum calcium, serum uric acid, cholesterol, serum phosphorus, and blood urea nitrogen, PIR was positively correlated with total spine BMD (ß = 0.004 95% CI: 0.001-0.007, P = 0.006). Individuals with the highest degree (college degree or above) had a 0.057 g/cm2 greater BMD than that of the lowest degree (less than 9th grade) (ß = 0.057 95% CI: 0.037-0.077, P < 0.001). CONCLUSIONS: Our study indicates that SES was positively associated with the lumbar BMD among American men. Clinicians, healthcare providers, and policymakers should consider the unequal SES of men when implementing osteoporosis prevention and treatment strategies.

Clock knockdown attenuated reactive oxygen species-mediated senescence of chondrocytes through restoring autophagic flux.

AIMS: Articular cartilage degeneration has been recognized as the primary pathological change in osteoarthritis (OA). Mechanisms that govern the shift from cartilage homeostasis to OA remain unknown. Previous studies have reported that intrinsic circadian clock in chondrocytes could function to optimize cartilage repair/remodeling to optimum times of day, but little is known about its molecular mechanisms. This study attempted to investigate the potential role and mechanism of circadian gene Clock in OA pathology. MATERIALS AND METHODS: The expression of Clock in OA chondrocytes and cartilage was detected by qRT-PCR, western blot and immunohistochemistry. Temporal gene expression changes were analyzed using qRT-PCR in chondrocytes transfected with siClock following dexamethasone synchronization. In addition, the effect of Clock knockdown on senescent phenotypes and autophagic flux was evaluated in chondrocytes treated with siClock or siCntrl. KEY FINDINGS: The expression of Clock was up-regulated in OA cartilage from humans and mouse models. Clock knockdown had no influence on rhythmic expression of the downstream genes in primary chondrocytes. We also found that Clock knockdown elevated antioxidant enzyme activities, diminished reactive oxygen species (ROS) production and attenuated senescence of chondrocytes via restoring autophagic flux. SIGNIFICANCE: Clock knockdown can attenuate ROS-mediated senescence of chondrocytes through restoring autophagic flux in non-circadian manner, providing a potential therapeutic target for OA.

Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies.

BACKGROUND: Knee osteoarthritis (OA) is a major cause of disability in the elderly, however, there are few studies to estimate the global prevalence, incidence, and risk factors of knee OA. METHODS: For this study, we searched PUBMED, EMBASE and SCOPUS from inception to April 4, 2020, without language restriction. We identified eligible studies with information on the prevalence or incidence of knee OA in population-based observational studies and extracted data from published reports. We did random-effects meta-analysis to generate estimates. This study was registered with PROSPERO (CRD42020181035). FINDINGS: Out of 9570 records identified, 88 studies with 10,081,952 participants were eligible for this study. The pooled global prevalence of knee OA was 16⋅0% (95% CI, 14⋅3%-17⋅8%) in individuals aged 15 and over and was 22⋅9% (95% CI, 19⋅8%-26⋅1%) in individuals aged 40 and over. Correspondingly, there are around 654⋅1 (95% CI, 565⋅6-745⋅6) million individuals (40 years and older) with knee OA in 2020 worldwide. The pooled global incidence of knee OA was 203 per 10,000 person-years (95% CI, 106-331) in individuals aged 20 and over. Correspondingly, there are around annual 86⋅7 (95% CI, 45⋅3-141⋅3) million individuals (20 years and older) with incident knee OA in 2020 worldwide. The prevalence and incidence varied substantially between individual countries and increased with age. The ratios of prevalence and incidence in females and males were 1⋅69 (95% CI, 1⋅59-1⋅80, p<0⋅00) and 1⋅39 (95% CI, 1⋅24-1⋅56, p<0⋅00), respectively. INTERPRETATION: Our study provides the global prevalence (16⋅0% [95% CI, 14⋅3%-17⋅8%]) and incidence (203 per 10,000 person-years [95% CI, 106-331]) of knee OA. These findings can be used to better assess the global health burden of knee OA. Further prospective cohort studies are warranted to identify modifiable risk factors for providing effectively preventive strategies in the early stages of the disease. FUNDING: This work was supported by grants from the National Natural Science Foundation of China (nos. 81772384 and 81572174).

Preparation and properties studies of UV-curable silicone modified epoxy resin composite system.

INTRODUCTION: Modified epoxy suitable for ultraviolet (UV) curing is prepared by using organic silicon toughening. The curing kinetics of the composite are studied by dielectric analysis (DEA), and the two-phase compatibility of the composite is studied by scanning electron microscopy (SEM). METHODS: The tensile properties, heat resistance, and humidity resistance of the cured product are explored by changing the composition ratio of the silicone and the epoxy resin. RESULTS: SEM of silicone/epoxy resin shows that the degree of cross-linking of the composites decreases with an increase of silicone resin content. Differential thermal analysis indicates that the glass transition temperature and the thermal stability of the composites decrease gradually with an increase of silicone resin content. The thermal degradation rate in the high temperature region, however, first decreases and then increases. In general, after adding just 10%-15% of the silicone resin and exposing to light for 15 min, the composite can still achieve a better curing effect. CONCLUSIONS: Under such conditions, the heat resistance of the cured product decreases a little. The tensile strength is kept constant so that elongation at breakage is apparently improved. The change rate after immersion in distilled water at 60°C for seven days is small, which shows excellent humidity resistance.