Association of the Dietary Index for Gut Microbiota with site-specific Osteoporosis: Insights from machine learning applied to a national population.

We aimed to systematically review available data on the association between vitamin C intake and bone mineral density (BMD), as well as risk of fractures and osteoporosis, and to summarise this information through a meta-analysis. Previous studies on vitamin C intake in relation to BMD and risk of fracture and osteoporosis were selected through searching PubMed, Scopus, ISI Web of Science and Google Scholar databases before February 2017, using MeSH and text words. To pool data, either a fixed-effects model or a random-effects model was used, and for assessing heterogeneity, Cochran's Q and I 2 tests were used. Subgroup analysis was applied to define possible sources of heterogeneity. Greater dietary vitamin C intake was positively associated with BMD at femoral neck (pooled r 0·18; 0·06, 0·30) and lumbar spine (pooled r 0·14; 95 % CI 0·06, 0·22); however, significant between-study heterogeneity was found at femoral neck: I 2=87·6 %, P heterogeneity<0·001. In addition, we found a non-significant association between dietary vitamin C intake and the risk of hip fracture (overall relative risk=0·74; 95 % CI 0·51, 1·08). Significant between-study heterogeneity was found (I 2=79·1 %, P heterogeneity<0·001), and subgroup analysis indicated that study design, sex and age were the main sources of heterogeneity. Greater dietary vitamin C intake was associated with a 33 % lower risk of osteoporosis (overall relative risk=0·67; 95 % CI 0·47, 0·94). Greater dietary vitamin C intake was associated with a lower risk of hip fracture and osteoporosis, as well as higher BMD, at femoral neck and lumbar spine.

ObjectivesTo investigate the associations of residential greenness with bone mineral density and incident osteoporosis, and further evaluate the potential modifying effect of genetic susceptibility.MethodsWe used the Normalised Difference Vegetation Index...

This study was aimed to examine the association of adherence to the dietary approaches to stop hypertension (DASH) dietary pattern and osteoporosis risk in postmenopausal Iranian women, hypothesizing that higher adherence to this pattern is associated with lower risk of postmenopausal osteoporosis. One hundred fifty-one postmenopausal Iranian women aged 50-85years participated in this cross-sectional study. Lumbar spine and femoral neck bone mineral densities (BMDs) were measured via dual-energy X-ray absorptiometry. Postmenopausal osteoporosis was then defined using the WHO criteria as a BMD T-score of ≤ - 2.5 standard deviations. The usual past-year dietary intakes were assessed by a valid and reliable 168-item food frequency questionnaire. The DASH score was then calculated based on energy-adjusted intakes of eight major dietary components usually emphasized (i.e., fruits, vegetables, nuts and legumes, low-fat dairy products, and whole grains) or minimized (i.e., sodium, sweets, and red or processed meats) in the DASH diet. The higher the DASH score of a participant, the higher the adherence to the DASH dietary pattern. After adjusting for several potential covariates in the multivariable-adjusted binary logistic regression analysis, participants in the highest tertile of DASH score had lower risk of osteoporosis at lumbar spine than those in the lowest tertile (odds ratio = 0.28; 95% confidence interval, 0.09-0.88; p = 0.029). However, no significant association was observed between adherence to the DASH dietary pattern and risk of osteoporosis at femoral neck. Findings suggest the inverse association of adherence to the DASH dietary pattern and osteoporosis risk in postmenopausal Iranian women.

This study investigated the relationship between serum uric acid (SUA) levels and osteoporosis (OP) risk through cross-sectional and Mendelian randomization (MR) analyses to address the unclear role of SUA in bone metabolism. Data from the 2015-2020 National Health and Nutrition Examination Survey were analyzed using multiple logistic regression, restricted cubic spline (RCS) modeling, and subgroup analyses. MR was performed using the inverse variance weighted method as the primary approach, complemented by diverse methods and sensitivity analyses. This study included 6,020 participants, of whom 1635 were diagnosed with OP. Based on the fully adjusted Model IV, individuals in the third (Q3) and fourth (Q4) quartiles exhibited a 38% (OR = 0.622; 95% CI: 0.423-0.915; P = 0.030) and 49% (OR = 0.513; 95% CI: 0.320-0.823; P = 0.015) lower risk of osteoporosis, respectively, relative to those in the lowest quartile (Q1) (Table 2). RCS analysis revealed an L-shaped inverse association (P-overall = 0.011; P-non-linear = 0.803) with a turning point around 5.3mg/dL. Subgroup analysis suggested that sex, race, diabetes status, and serum cholesterol levels were potential effect modifiers (P-interaction < 0.05). MR analysis further demonstrated a significant causal protective effect of SUA levels on OP (OR = 0.870; 95% CI: 0.776-0.974, P = 0.016). This study provides new evidence that higher SUA levels are associated with reduced risk of OP, offering potential implications for future preventive strategies. Key Points • Higher serum uric acid levels were independently associated with a lower risk of osteoporosis. • Gender, race, diabetes status, and serum cholesterol levels are factors that affect the negative association between serum uric acid and osteoporosis. • Mendelian randomization analysis supported a causal protective effect of serum uric acid levels on osteoporosis.

BackgroundRecent research suggests that omega-3 fatty acids may play a role in bone metabolism through their influence on bone mineral density (BMD) and the regulation of bone turnover markers. However, epidemiological evidence linking omega-3 intake to the risk of developing osteoporosis is still emerging and remains inconclusive. This study aims to clarify the role of dietary omega-3 fatty acids in the prevention of osteoporosis.MethodsWe analyzed data from 8,889 participants categorized into normal, osteopenia, and osteoporosis groups based on their BMD scores from the National Health and Nutrition Examination Survey (NHANES). We measured dietary omega-3 intake using two 24-h dietary recall interviews. Dietary omega-3 intake was quantified and divided into quartiles. Multivariate logistic regression and subgroup analysis were used to explore the correlation between dietary omega-3 intake and osteoporosis. The dose–response relationship between the two was analyzed with a restricted cubic spline (RCS).ResultsHigher dietary intake of omega-3 fatty acids was inversely associated with the risk of osteoporosis. Participants in the highest quartile of omega-3 intake had a significantly lower risk (OR = 0.71, 95% CI: 0.53–0.93) compared to those in the lowest quartile, with a consistent trend across all adjusted models (p for trend <0.05). Subgroup analyses indicated stronger associations in individuals under 60 years of age, female and non-smokers. In individuals aged under 60, higher omega-3 intake was associated with significantly reduced osteoporosis risk (OR = 0.51, 95%CI: 0.26–0.95), females showed a protective effect of high omega-3 intake against osteoporosis (OR = 0.65, 95% CI: 0.49–0.87). Among non-smokers, higher omega-3 intake was associated with a lower risk of osteoporosis (OR = 0.64, 95% CI: 0.45–0.90), whereas in smokers, the association was not evident (OR = 0.91, 95%CI: 0.55–1.52). No significant associations were found in older participants or smokers. Intake of omega-3 and osteoporosis were linearly related (p for nonlinear = 0.366).ConclusionThis study demonstrates a significant inverse relationship between dietary omega-3 fatty acid intake and osteoporosis risk, suggesting omega-3 s play a crucial role in bone health. However, further longitudinal studies are needed to confirm these findings and refine dietary recommendations for osteoporosis prevention.

Previous studies may have overestimated the effect of age at menopause when assessing osteoporosis risk and may have overlooked women with late menopause as a high-risk group. Therefore, we aim to clarify the association between age at menopause and osteoporosis risk, as well as to identify key characteristics of individuals with osteoporosis. This study utilized a nationally representative cross-sectional sample, including 5,804 postmenopausal women aged 55-79 years. Weighted multivariate linear regression and logistic regression models were used to assess the association between age at menopause and femoral neck BMD and osteoporosis. Core characteristics of the osteoporosis population were identified by calculating standardized coefficients and applying SHapley additive interpretation (SHAP) analysis. Restricted cubic spline (RCS) analysis and subgroup analysis were conducted on these core characteristics. The age at menopause showed no significant association with osteoporosis risk in any model (P > 0.05). the two primary modifiable factors associated with reduced osteoporosis risk were BMI(OR = 0.84, 95% CI: 0.80-0.88) and hormone-use history (OR = 0.50, 95% CI: 0.33-0.74). Furthermore, RCS analyses revealed significant nonlinear relationships between age at menopause and both BMI (P < 0.001) and hormone-use history (P < 0.001). Subgroup analyses indicated that the compensatory effects of these two factors varied across different specific subgroups. This study reveals that the initial protective advantage in reducing osteoporosis risk conferred by a later age at menopause diminishes in later life. Maintaining a higher BMI and appropriate hormone therapy can effectively compensate for the initial risk disadvantage.

Higher dietary fish consumption is associated with a lower risk of osteoporosis: A meta-analysis of observational studies.

The study aimed to investigate the relationship between dietary oxidative balance score (DOBS) and the risk of osteoporosis in American postmenopausal women. A total of 3043 participants were included in this study. The linear relationship between DOBS and femur BMD was evaluated using a weighted multivariate linear regression model. The association between DOBS and the risk of osteoporosis was assessed using a weighted logistic regression model, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. Moreover, the relationship was further characterized through smooth curve fitting (SCF) and weighted generalized additive model (GAM) analysis. After adjusting for all covariates, the weighted multivariable linear regression models showed a positive correlation between DOBS and femur BMD. Moreover, the weighted logistic regression model demonstrated that compared to the first tertile of DOBS, the highest tertile of DOBS was significantly associated with a lower risk of osteoporosis, with ORs of 0.418 (95% CI, 0.334, 0.522) for individuals under the age of 70 and 0.632 (95% CI, 0.506, 0.790) for individuals aged 70 or above. Similar trends were also observed in SCF and GAM models. The present study indicated that postmenopausal women with a higher DOBS have a lower risk of femur osteoporosis. This finding may highlight the potential protective role of an antioxidant-rich diet for the bones of the postmenopausal population. Moreover, DOBS may also be a valuable tool in identifying individuals with osteoporosis. Screening and early intervention for osteoporosis may be essential for postmenopausal women with low DOBS.

Bone mineral density (BMD) is an important indicator of bone health, and a decrease in BMD is closely associated with an increased risk of osteoporosis (OP) and fractures. Although BMD decline is typically age-related, the issue of decreased bone density is becoming increasingly prominent in younger populations. Chronic inflammation is considered one of the key factors contributing to decreased bone density. The neutrophil percentage to albumin ratio (NPAR), as an inflammatory marker, has gained attention in recent years for its role in various diseases. However, research on its relationship with bone density remains limited. This study aims to explore the association between NPAR and decreased bone density, and to provide potential biomarkers for early screening of OP. Finally, Mendelian randomization (MR) was employed to assess the independent causal effects of neutrophil percentage and albumin levels on OP. This study is based on data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018, including 10,961 eligible adults. BMD was assessed using dual-energy X-ray absorptiometry (DXA), and NPAR was calculated based on neutrophil percentage and serum albumin levels. The non-linear relationship between NPAR and BMD was analyzed using restricted cubic splines (RCS), and multivariable linear regression and logistic regression models were used to assess their association. Additionally, gender-stratified analyses were performed, and subgroup and threshold analyses were conducted to explore the relationship between NPAR and OP in different genders. MR revealed that elevated neutrophil percentage significantly increased the risk of OP, whereas higher albumin levels were associated with a reduced OP risk. Restricted cubic spline analysis revealed a negative association between NPAR and BMD, with a significant non-linear inflection point occurring at approximately NPAR = 1.0. Further multivariable regression analysis showed that, in the unadjusted model, NPAR was negatively associated with BMD. However, after adjusting for demographic factors, the relationship reversed, showing a marginally significant positive association. After full adjustment, the association between NPAR and BMD was no longer significant, suggesting that demographic and lifestyle factors play an important confounding role in the relationship between NPAR and bone density. Additionally, gender-stratified analysis using multivariable regression indicated that the association between NPAR and low BMD/OP was more significant in men, whereas no statistical significance was found in women. Subgroup analysis suggested that hypertension, obesity, and older age might exacerbate the impact of NPAR on OP. Threshold analysis found that in women, NPAR ≥ 1.49 was significantly associated with OP risk (OR = 2.89, P = 0.016), while no clear threshold effect was observed in men. This study found a complex relationship between NPAR and bone mineral density, with the association being influenced by various demographic and lifestyle factors. In men, NPAR may be associated with low BMD/OP through inflammatory responses, while in women, this association is more influenced by additional covariates. As a composite inflammatory-nutritional biomarker, NPAR may hold potential for osteoporosis screening and risk prediction, but further research is needed to validate its clinical application value.

Fasting glucose level and the risk of incident osteoporosis in the Koreans.

BackgroundOsteoporosis characterized by deteriorating bone loss is becoming one of the serious health problems globally. Vitamin B2, also known as riboflavin, exhibiting multiple prominent physiological traits such as antioxidant effects, reducing lipid peroxidation and regulating glutathione redox cycle, allows it to be a potential agent to improve bone loss. However, the relationship between dietary vitamin B2 intake and osteoporosis remains unelucidated. The objective of this study was to explore the association between the dietary intake of vitamin B2 and bone loss in the U.S. female adults using the National Health and Nutrition Examination Survey (NHANES) database.MethodsFemale participants with complete information on dietary vitamin B2 intake, dual-energy X-ray absorptiometry, and other essential covariates from NHANES database were included in the current study. Multivariable logistic regression and linear regression analyses were conducted to assess the relationships of dietary vitamin B2 intake with osteoporosis and bone mineral density (BMD) levels, respectively. Subgroup analyses, interaction tests, and restricted cubic spline (RCS) regression analyses were further used to verify the stability, robustness and potential nonlinearity of the association. Mediation analysis was performed to probe the role of serum alkaline phosphatase (ALP) in the aforementioned relationship, and the network pharmacology analysis was also conducted to determine the potential pathways and key targets for vitamin B2 regulating bone health.ResultsA total of 4, 241 female participants from four NHANES cycles were included in this study. After multivariate adjustment, the intake of vitamin B2 was beneficially associated with reduced risk for femur osteoporosis (ORQ4 vs. Q1=0.613; 95%CI: 0.454–0.829). A higher intake of vitamin B2 (quartile 4) was significantly correlated with decreased risk of reduced femoral BMD levels, with the β being 0.020 (95%CI: 0.007–0.033), 0.015 (95%CI: 0.002–0.027), 0.020 (95%CI: 0.009–0.031) and 0.022 (95%CI: 0.006–0.037) for the BMD of total femur, femoral neck, trochanter, and intertrochanter, respectively (all P value < 0.05). Covariate total MET was found to modify the association between vitamin B2 intake and osteoporosis (P interaction = 0.0364), with the aforementioned relationship being more pronounced in the subgroup of insufficiently active individuals. Furthermore, RCS analysis revealed that vitamin B2 intake was positively and linearly associated with reduced risk for femoral OP and increased BMD levels of total femur, trochanter and intertrochanter, while positively and nonlinearly correlated with increased BMD level of femoral neck. Additionally, the association between vitamin B2 intake, osteoporosis and BMD levels was mediated by ALP, with a mediation proportion of 12.43%, 7.58%, 12.17%, 7.64%, and 6.99% for OP, total femur, femoral neck, trochanter, and intertrochanter BMD, respectively. Finally, network pharmacology analysis indicated that vitamin B2 regulating bone health mainly through pathways like HIF-1 signaling pathway, longevity regulating pathway, p53 signaling pathway, etc.ConclusionsHigher intake of vitamin B2 is positively associated with reduced risks for femoral osteoporosis and bone loss. Vitamin B2 may represent a modifiable lifestyle factor for the prevention and management of osteoporosis.

BackgroundAged osteoporosis poses a significant threat to the well-being and longevity of older individuals, yet evidence regarding the relationship between osteoporosis risk and mortality among the elderly population in Asia remains unknown.AimsOur study aimed to investigate associations between osteoporosis risk and all-cause mortality, as well as cause-specific mortality, among the Chinese elderly population.MethodsPooled data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted between 2002 and 2018 were utilized to analyze the associations between osteoporosis risk and all-cause, heart disease, cardiovascular disease (CVD), respiratory disease, and cancer mortality. Cox proportional hazards models were employed for this analysis. Osteoporosis risk was assessed using the Osteoporosis Self-Assessment Tool for Asians (OSTA). Restricted cubic spline (RCS) functions were applied to explore the nonlinear relationship between OSTA and mortality. The robustness of the Cox models was evaluated through internal verification, subgroup analyses, and sensitivity analyses.ResultsA total of 12,711 elderly individuals aged ≥ 65 years were included for analysis at baseline. During a 16-year follow-up, 7,963 individuals in the cohort were identified as deceased. Compared to those with low osteoporosis risk, elderly individuals with high osteoporosis risk demonstrated a significantly elevated risk of all-cause, heart disease, CVD, respiratory disease and cancer mortality. The relationship between OSTA level and all-cause and cause-specific mortality exhibited a significant L-shaped pattern.ConclusionsThe risk of osteoporosis is independently associated with the prediction of mortality. The OSTA may serve as a suitable predictor for mortality related to osteoporosis among the Asian population.

This study aimed to examine associations between plasma sex-related hormones with bone mineral density (BMD) and risks of osteoporosis or osteopenia in men and postmenopausal women patients with type 2 diabetes mellitus (T2DM). Baseline information on an ongoing cohort of 149 men and 102 postmenopausal women with T2DM in Xiamen, China were analyzed. Plasma estradiol (E2), total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) were measured. BMD of lumbar spine (L2-4), femoral neck (FN) and total hip (TH) were determined by dual-energy X-ray absorptiometry (DXA). Osteoporosis or osteopenia was defined as the minimum T-scores of BMD of these three different sites of -1.0 or below. T2DM patients with osteoporosis/osteopenia (66.4% in men and 79.4% in postmenopausal women), compared to those without, showed significantly decreased level of E2 (75.3±28.9 vs. 107.8±25.9pmol/L and 18.4 (18.4-29.5) vs. 22.8 (18.4-40.5) pmol/L for men and postmenopausal women, respectively, both p-values <0.05), but not other sex-related hormones (including T, FSH, LH, or PRL). For all T2DM patients together and men separately, multivariable linear regression and logistic regression analyses showed that higher E2 levels were significantly associated with higher BMD T-scores in L2-4, FN, TH and minimum of these three different sites, lower 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HFs) estimated by Fracture Risk Assessment Tool score, as well as decreased risk of osteoporosis/osteopenia. As for postmenopausal women T2DM patients, E2 level was positively associated with BMD T-scores in L2-4 and minimum of three different sites but was not independently associated with risk of osteoporosis/osteopenia. Higher plasma E2 was significantly associated with increased BMD and lower risk of osteoporosis or osteopenia in T2DM patients, especially for men. Screening of BMD and estradiol levels as well as evaluating risks of osteoporosis/osteopenia are important for T2DM patients.

We examined the cross-sectional association of the intakes of different types of fishes with bone mass and osteoporosis risk in postmenopausal Chinese women. We found that higher intake of sea fish is independently associated with greater bone mass and lower osteoporosis risk among postmenopausal Chinese women. Fish contains many important nutrients that are beneficial on bone health, but limited data on the relationship between fish intake and bone health are available. We examined the association of the intakes of different types of fishes with bone mineral density (BMD) and bone mineral content (BMC) and osteoporosis risk. This population-based cross-sectional study was conducted among 685 postmenopausal Chinese women. Habitual dietary intakes were assessed using food frequency questionnaire. BMD and BMC at the whole body, lumbar spine, and left hip were measured with dual-energy x-ray absorptiometry. After adjusting for the potential confounders, we observed dose-dependent relations between sea fish intake and BMDs, BMCs, and osteoporosis risk; the mean BMDs were 3.2-6.8% higher, and BMCs 5.1-9.4% higher in the top quintile groups (Q5) of sea fish intake than in the bottom quintile (Q1) at the whole body and hip sites (p < 0.05); the odds ratios (95% confidence interval (CI)) for osteoporosis (T-score < -2.5) in Q5 were 0.23 (0.08-0.66), 0.12 (0.03-0.59), and 0.06 (0.01-0.44) compared with those in Q1 at the whole body, total hip, and femur neck, respectively. No independent association between consumption of freshwater fish or shellfish and bone mass was observed. Higher intake of sea fish is independently associated with greater bone mass and lower osteoporosis risk among postmenopausal Chinese women.

This study aimed to explore the associations of genetic variants in the semaphorin 3A (SEMA3A) signaling pathway genes, including SEMA3A, NRP1, PLXNA1, PLXNA2 and PLXNA3 with osteoporosis (OP) risk and bone mineral density (BMD) in a Chinese Han older adult population. A two-stage design was adopted. Total of 47.8kb regions in the 5 genes were sequenced using targeted next-generation sequencing (NGS) technology in the discovery stage, and the discovered OP-related single nucleotide polymorphisms (SNPs) were further genotyped using improved multiple linkage detection reaction technique in the validation stage. Methods of ALP/TRAP staining, real-time fluorescent quantitative PCR, and cell proliferation and apoptosis assays were performed with MC3T3-E1 and RAW 264.7 cell lines to clarify biological effects of observed functional variants in cell lines responsible for bone mass remodeling. Total of 400 postmenopausal women (211 OP cases) were involved in the discovery stage, where 6 common and 4 rare genetic variants were found to be associated with OP risk. In the validation stage among another 859 participants (417 women, 270 OP cases), the PLXNA2 rs2274446 T allele was associated with reduced OP risk and increased femoral neck (FN) BMD compared to the C allele. Moreover, significant associations of NRP1 rs2070296 with FN BMD/OP risk and of NRP1 rs180868035 with lumbar spine and FN BMDs were also observed in the combination dataset analysis. Compared to the osteoblasts/osteoclasts transfected with the wild-type NRP1 rs180868035, those transfected with the mutant-type had reduced mRNA expression of osteoblastic genes (i.e., ALP, RUNX2, SP7 and OCN), while elevated mRNA expression of osteoclastic genes (i.e., TRAP, NFATc1 and CTSK). Furthermore, mutant NRP1 rs180868035 transfection inhibited osteoblast proliferation and osteoclast apoptosis, while promoted osteoclast proliferation and osteoblast apoptosis in corresponding cell lines. Genetic variants located in NRP1 and PLXNA2 genes were associated with OP risk and BMD. The NRP1 rs180868035 affects bone metabolism by influencing osteoblasts and osteoclasts differentiation, proliferation and apoptosis.