The Gut Microbiome Is Altered in Postmenopausal Women With Osteoporosis and Osteopenia.
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ABSTRACT:
SUBMITTER: Rettedal EA
PROVIDER: S-EPMC7990138 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:For the purpose of providing evidence for the treatment of osteoporosis and osteopenia, this study retrospectively identified succinylation-modified sites and proteins in postmenopausal women, and bioinformatics analysis were performed. METHODS:From January 2016 to June 2018, a total of 30 postmenopausal women aged from 55 to 70?years old were assigned to three groups: 10 cases with osteoporosis; 10 cases with osteopenia; and 10 cases with normal bone mass. Subsequently, the serum samples were collected from all cases for succinyl-proteome. Measures comprised label-free quantitative analysis, succinylation enrichment techniques, the liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) methods, and bioinformatics. RESULTS:A total of 113 succinylation sites on 35 proteins were identified based on quantitative information. The variation of the different multiple folds were more than 1.2 times as a significant increase for up-regulated and less than 1/1.2 times as a significant decrease for down-regulated. Among the quantified succinylation sites, 66 were up-regulated and 11 down-regulated in the Osteopenia/Normal comparison group, 24 were up-regulated and 44 down-regulated in the Osteoporosis/Osteopenia comparison group, 45 were up-regulated and 32 down-regulated in the Osteoporosis/Normal comparison group. Among the quantified succinylation proteins, 24 were up-regulated and 7 down-regulated in the Osteopenia/Normal comparison group, 15 were up-regulated and 20 down-regulated in the Osteoporosis/Osteopenia comparison group, 20 were up-regulated and 17 down-regulated in the Osteoporosis/Normal comparison group. The percentage of proteins differed in immune response, signaling pathway, proteolysis, lymphocyte, leukocyte, and cell activation. Four differentially expressed proteins (apolipoprotein A-I, apolipoprotein A-II, hemoglobin subunit alpha, and haptoglobin) contained quantitative information; they were mediated with receptors, factors, mechanisms, that related to bone metabolism. Hemoglobin subunit alpha was screened for diagnosis of osteopenia. CONCLUSIONS:The succinyl-proteome experimental data indicated that apolipoprotein A-I, apolipoprotein A-II, hemoglobin subunit alpha, and haptoglobin were valuable for diagnosis and treatment in postmenopausal women with osteoporosis and osteopenia.
| S-EPMC6819194 | biostudies-literature
Project description:BackgroundIn South Korea, women aged 66 years are eligible for complimentary bone mineral density (BMD) screening via the National Screening Program for Transitional Ages. We aimed to evaluate the 10-year fracture risk in women receiving BMD screening between January 2008 and December 2015.MethodsBMD was classified as normal (T-score ≥-1.0 standard deviation [SD]), osteopenia (T-score <-1.0 SD and >-2.5 SD), and osteoporosis (T score ≤-2.5 SD) from dual-energy X-ray absorptiometry. Follow-up continued from the screening date until a diagnosis for clinical fragility fracture (including sites of the vertebrae, hip, pelvis, clavicle, humerus, forearm, wrist, lower leg, and ankle), censored at the earliest date of trauma, death, or December 2017; fracture was ascertained using diagnostic codes from the National Health Insurance Service database. A multivariable Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of fracture in women with osteopenia or osteoporosis relative to women with normal BMD.ResultsAmong the 271,197 women screened, 44.0% had osteopenia and 35.2% had osteoporosis. The 10 year cumulative incidence of fragility fractures was 31.1%, 37.5%, and 44.3% in women with normal BMD, osteopenia, and osteoporosis, respectively. Fracture risk was higher in women with osteopenia (HR, 1.31; 95% CI, 1.28 to 1.34) and osteoporosis (HR, 1.68; 95% CI, 1.64 to 1.72) than in women with normal BMD.ConclusionWomen with osteopenia and women with osteoporosis, identified by the national BMD screening program, demonstrated a substantially elevated risk of fracture.
| S-EPMC8743593 | biostudies-literature
Project description:Growing evidence suggests that the gut microbiota and their metabolites are associated with bone homeostasis and fragility. However, this association is limited to microbial taxonomic differences. This study aimed to explore whether gut bacterial community associations, composition, and functions are associated with osteopenia and osteoporosis. We compared the gut bacterial community composition and interactions of healthy postmenopausal women with normal bone density (n = 8) with those of postmenopausal women with osteopenia (n = 18) and osteoporosis (n = 21) through 16S rRNA sequencing coupled with network biology and statistical analyses. The results of this study showed reduced alpha diversity in patients with osteoporosis, followed by that in patients with osteopenia, then in healthy controls. Taxonomic analysis revealed that significantly enriched bacterial genera with higher abundance was observed in patients with osteoporosis and osteopenia than in healthy subjects. Additionally, a co-occurrence network revealed that, compared to healthy controls, bacterial interactions were higher in patients with osteoporosis, followed by those with osteopenia. Further, NetShift analysis showed that a higher number of bacteria drove changes in the microbial community structure of patients with osteoporosis than osteopenia. Correlation analysis revealed that most of these driver bacteria had a significant positive relationship with several significant metabolic pathways. Further, ordination analysis revealed that height and T-score were the primary variables influencing the gut microbial community structure. Taken together, this study evaluated that microbial community interaction is more important than the taxonomic differences in knowing the critical role of gut microbiota in postmenopausal women associated with osteopenia and osteoporosis. Additionally, the significantly enriched bacteria and functional pathways might be potential biomarkers for the prognosis and treatment of postmenopausal women with osteopenia and osteoporosis.
| S-EPMC9959971 | biostudies-literature
Project description:The UDP-glucuronosyltransferase 1A1 (UGT1A1) is involved in the process of estrogen conjugation and elimination. The aim of the study was to analyze whether the UGT1A1 genetic variants are associated with the development of osteopenia and osteoporosis in postmenopausal women. The analysis of the rs4148323 (UGT1A1*6) and rs3064744 (UGT1A1*28) variants in the UGT1A1 gene was conducted using real-time PCR. A significant correlation was observed between the genotypes of the rs3064744 (UGT1A1*28) sequence variant and body mass in women with osteoporosis. The analysis of the Z-score values revealed that women with osteoporosis and carrying the 6/6 variant had the lowest Z-score values as compared to women with the 6/7 and the 7/7 variants (- 1.966 ± 0.242 vs. - 1.577 ± 0.125 and - 1.839 ± 0.233). In addition, the odds ratio for the investigated genotypes (6/6, 6/7, 7/7) indicated an increased risk for osteopenia and osteoporosis in women with the 7/7 homozygous genotype. The analysis of the frequencies of the GG, GA and AA genotypes of the rs4148323 UGT1A1 gene showed no statistically significant differences between the groups. Our analysis revealed that the UGT1A1 rs3064744 variant may affect the risk of developing osteoporosis in postmenopausal Polish women. The UGT1A1 rs4148323 variant is not directly associated with the development of osteopenia and osteoporosis.
| S-EPMC8405802 | biostudies-literature
Project description:BackgroundThe objective of the present study was to investigate whether associations exist between inflammatory biomarkers and all-cause mortality and cardiovascular disease (CVD) mortality in women with postmenopausal osteoporosis (PMOP) or osteopenia.MethodsIn this retrospective cohort study, data were obtained from the National Health and Nutrition Examination Survey database from the years 2007 to 2010, 2013 to 2014, and 2017 to 2018. The inflammatory biomarkers including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), neutrophil × platelet/lymphocyte (SII), neutrophil × monocyte/lymphocyte (SIRI), and neutrophil × monocyte × platelet/lymphocyte ratio (AISI) were calculated.ResultsA total of 2,834 women were included, with a median survival of 113.51 (3.15) months. During follow-up, 602 women died of all-cause mortality and 185 women died of CVD. NLR, MLR, SIRI, and AISI were significantly associated with all-cause mortality in postmenopausal women with osteoporosis or osteopenia. NLR, MLR, SIRI, and AISI were related to CVD mortality in postmenopausal women with osteoporosis or osteopenia (All P < 0.05). Based on the results of the subgroup analysis, AISI, SIRI, and MLR were associated with all-cause mortality and CVD mortality in postmenopausal women with PMOP or osteopenia who had a history of CVD and diabetes. AISI, SII, MLR, and NLR were associated with all-cause mortality and CVD mortality in PMOP or osteopenia women with a body mass index (BMI) > 25 kg/m2. PLR was associated with all-cause mortality in PMOP or osteopenia women aged ≥ 65 years.ConclusionInflammatory biomarkers were correlated with mortality risk in the PMOP or osteopenia population. This finding may be helpful for the prognosis management of PMOP or osteopenia in postmenopausal women.
| S-EPMC10500848 | biostudies-literature
Project description:Nutrient patterns (NPs) and the synergistic effect between nutrients have been shown to be associated with changes in bone mineral density (BMD). This study aimed to identify NPs and to associate them with BMD categories in postmenopausal women. This cross-sectional, observational, analytical study was carried out with women in menopause for at least 12 months, aged ≥50 years. Sociodemographic, lifestyle, and clinical variables were investigated. BMD was assessed using dual energy X-ray absorptiometry. A dietary assessment was conducted using a food frequency questionnaire, and three nutrient patterns (NP1, NP2, and NP3) were extracted from the principal component analysis. Multivariate logistic regression was applied to investigate the association between BMD classifications and NP consumption. A total of 124 women, aged on average, 66.8 ± 6.1 years, were evaluated. Of these, 41.9% had osteopenia and 36.3% had osteoporosis. The NP1 (OR: 6.64, [CI95%: 1.56-28.16]; p = 0.010), characterized by vitamin B12, pantothenic acid, phosphorus, riboflavin, protein (total and animal), vitamin B6, potassium, vitamin D, vitamin E, calcium, cholesterol, β-carotene, omega 3, magnesium, zinc, niacin, and selenium; and the NP2 (OR: 5.03, [CI95%: 1.25-20.32]; p = 0.023), characterized by iron, vegetable protein, thiamine, folate, fibers (soluble and insoluble), PUFA, vitamin A, vitamin K, alpha-tocopherol, copper, sodium, and retinol, was inversely associated with osteopenia. The lower consumption of NP1 and NP2 by postmenopausal women was associated with a higher risk of osteopenia, but not osteoporosis.
| S-EPMC10096860 | biostudies-literature
Project description:Some evidence suggests that bone health can be regulated by gut microbiota. To better understand this, we performed 16S ribosomal RNA sequencing to analyze the intestinal microbial diversity in primary osteoporosis (OP) patients, osteopenia (ON) patients and normal controls (NC). We observed an inverse correlation between the number of bacterial taxa and the value of bone mineral density. The diversity estimators in the OP and ON groups were increased compared with those in the NC group. Beta diversity analyses based on hierarchical clustering and principal coordinate analysis (PCoA) could discriminate the NC samples from OP and ON samples. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria constituted the four dominant phyla in all samples. Proportion of Firmicutes was significantly higher and Bacteroidetes was significantly lower in OP samples than that in NC samples (p < 0.05), Gemmatimonadetes and Chloroflexi were significantly different between OP and NC group as well as between ON and NC group (p < 0.01). A total of 21 genera with proportions above 1% were detected and Bacteroides accounted for the largest proportion in all samples. The Blautia, Parabacteroides and Ruminococcaceae genera differed significantly between the OP and NC group (p < 0.05). Linear discriminant analysis (LDA) results showed one phylum community and seven phylum communities were enriched in ON and OP, respectively. Thirty-five genus communities, five genus communities and two genus communities were enriched in OP, ON and NC, respectively. The results of this study indicate that gut microbiota may be a critical factor in osteoporosis development, which can further help us search for novel biomarkers of gut microbiota in OP and understand the interaction between gut microbiota and bone health.
| S-EPMC5474093 | biostudies-literature
Project description:UNLABELLED: This posthoc analysis of four trials studied the efficacy of risedronate to reduce fragility fractures in postmenopausal women with osteopenia (i.e., T-scores between -1 and -2.5). Risedronate reduced the fracture risk by 73% (p = 0.023) in this population of women with low femoral neck bone mass and no prevalent vertebral fractures. INTRODUCTION: Low bone mass represents an increasing health risk and burden. Half of fragility fractures occur in osteopenic women underscoring the need for treatments reducing fracture risk. This analysis reports the effect of risedronate to reduce fragility fracture risk in osteopenic women without prevalent vertebral fractures. METHODS: Postmenopausal women with osteopenia, defined as femoral neck T-score between -1 and -2.5 by DXA and no prevalent vertebral fractures, were identified from four controlled randomized trials (BMD Multinational, BMD North America, VERT Multinational and VERT North America). The risk reduction for fragility fractures in patients receiving 5 mg risedronate daily for 1.5 to 3 years compared to placebo was assessed. An additional sensitivity analysis excluded patients who were osteopenic at the femoral neck but had a BMD lower than -2.5 SD at the lumbar spine. RESULTS: Six hundred and twenty postmenopausal women with osteopenia were included, receiving either placebo (n = 309) or risedronate 5 mg (n = 311). Risedronate reduced the risk of fragility fractures by 73% over 3 years versus placebo (p = 0.023); cumulative fragility fracture incidence was 6.9% in placebo-treated versus 2.2% in risedronate-treated patients. The magnitude of the effect was similar in the sensitivity analysis subset. CONCLUSION: Risedronate significantly reduced the risk of fragility fractures in postmenopausal women with osteopenia (femoral neck T-score between -1 and -2.5 SD) and no prevalent vertebral fractures.
| S-EPMC2277453 | biostudies-other
Project description:Oral risedronate is effective in the treatment of postmenopausal osteoporosis when administered daily, weekly, or monthly. In this 1-year, randomized, double-blind, multicenter study we compared the weekly 35-mg and daily 5-mg risedronate dosing regimens in the treatment of Chinese postmenopausal women with osteoporosis or osteopenia.Postmenopausal women with primary osteoporosis or osteopenia were randomly assigned to the weekly group or daily group (n=145 for each) that received oral risedronate 35 mg once a week or 5 mg daily, respectively, for 1 year. The subjects' bone mineral densities (BMDs), bone turnover markers (P1NP and β-CTX), new vertebral fractures, and adverse events were assessed at baseline and during the treatments.All subjects in the weekly group and 144 subjects in the daily group completed the study. The primary efficacy endpoint after 1 year, ie the mean percent changes in the lumbar spine BMD (95% CI) were 4.87% (3.92% to 5.81%) for the weekly group and 4.35% (3.31% to 5.39%) for the daily group. The incidences of clinical adverse events were 48.3% in the weekly group and 54.2% in the daily group.The weekly 35-mg and daily 5-mg risedronate dosing regimens during 1 year of follow-up show similar efficacy in improving BMDs and biochemical markers of bone turnover in Chinese postmenopausal women with osteoporosis or osteopenia. Moreover, the two dosing regimens exhibit similar safety and tolerability.
| S-EPMC4648111 | biostudies-other
Project description:BackgroundIncreasing evidence suggests that gut microbiota play a role in the pathogenesis of breast cancer. The composition and functional capacity of gut microbiota associated with breast cancer have not been studied systematically.MethodsWe performed a comprehensive shotgun metagenomic analysis of 18 premenopausal breast cancer patients, 25 premenopausal healthy controls, 44 postmenopausal breast cancer patients, and 46 postmenopausal healthy controls.ResultsMicrobial diversity was higher in breast cancer patients than in controls. Relative species abundance in gut microbiota did not differ significantly between premenopausal breast cancer patients and premenopausal controls. In contrast, relative abundance of 45 species differed significantly between postmenopausal patients and postmenopausal controls: 38 species were enriched in postmenopausal patients, including Escherichia coli, Klebsiella sp_1_1_55, Prevotella amnii, Enterococcus gallinarum, Actinomyces sp. HPA0247, Shewanella putrefaciens, and Erwinia amylovora, and 7 species were less abundant in postmenopausal patients, including Eubacterium eligens and Lactobacillus vaginalis. Acinetobacter radioresistens and Enterococcus gallinarum were positively but weakly associated with expression of high-sensitivity C-reactive protein; Shewanella putrefaciens and Erwinia amylovora were positively but weakly associated with estradiol levels. Actinomyces sp. HPA0247 negatively but weakly correlated with CD3+CD8+ T cell numbers. Further characterization of metagenome functional capacity indicated that the gut metagenomes of postmenopausal breast cancer patients were enriched in genes encoding lipopolysaccharide biosynthesis, iron complex transport system, PTS system, secretion system, and beta-oxidation.ConclusionThe composition and functions of the gut microbial community differ between postmenopausal breast cancer patients and healthy controls. The gut microbiota may regulate or respond to host immunity and metabolic balance. Thus, while cause and effect cannot be determined, there is a reproducible change in the microbiota of treatment-naive patients relative to matched controls.
| S-EPMC6080540 | biostudies-literature