The importance of the UGT1A1 variants in the development of osteopenia and osteoporosis in postmenopausal women.
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ABSTRACT:
SUBMITTER: Bogacz A
PROVIDER: S-EPMC8405802 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Osteoporosis and its precursor osteopenia are common metabolic bone diseases in postmenopausal women. A growing body of evidence suggests that the gut microbiota is involved in the regulation of bone metabolism; however, there are few studies examining how gut microbiomes in osteoporosis and osteopenia may differ from those in healthy individuals. The aim of this study was to characterize the diversity, composition, and functional gene potential of the gut microbiota of healthy, osteopenic, and osteoporotic women. Body composition, bone density, and fecal metagenomes were analyzed in 86 postmenopausal women. The women were classified as healthy, osteopenic, or osteoporotic based on T-scores. The taxonomic and functional gene compositions of the microbiome were analyzed using shotgun metagenomic sequencing. Both osteoporotic and osteopenic taxonomic compositions were found to be significantly different from healthy participants. Linear discriminant-analysis effect-size analyses identified that healthy participants had more unclassified Clostridia and methanogenic archaea (Methanobacteriaceae) than in both osteoporotic and osteopenic participants. Bacteroides was found to be more abundant in osteoporosis and osteopenia groups. Some KEGG pathways, including carbohydrate metabolism, biosynthesis of secondary metabolites, and cyanoamino acid metabolism, were found to be more abundant in both osteoporosis and osteopenia. These results show that osteoporosis and osteopenia alter the gut microbiome of postmenopausal women and identify potential microbial taxonomic and functional pathways that may be involved in this disease. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
| S-EPMC7990138 | biostudies-literature
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: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: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:BackgroundLimited data are available regarding the cost-effectiveness of preventative therapies for postmenopausal women with osteopenia. The objective of the present study was to evaluate the cost-effectiveness of raloxifene, alendronate and conservative care in this population.MethodsWe developed a microsimulation model to assess the incremental cost and effectiveness of raloxifene and alendronate relative to conservative care. We assumed a societal perspective and a lifetime time horizon. We examined clinical scenarios involving postmenopausal women from 55 to 75 years of age with bone mineral density T-scores ranging from -1.0 to -2.4. Modeled health events included vertebral and nonvertebral fractures, invasive breast cancer, and venous thromboembolism (VTE). Raloxifene and alendronate were assumed to reduce the incidence of vertebral but not nonvertebral fractures; raloxifene was assumed to decrease the incidence of breast cancer and increase the incidence of VTEs. Cost-effectiveness is reported in $/QALYs gained.ResultsFor women 55 to 60 years of age with a T-score of -1.8, raloxifene cost approximately $50,000/QALY gained relative to conservative care. Raloxifene was less cost-effective for women 65 and older. At all ages, alendronate was both more expensive and less effective than raloxifene. In most clinical scenarios, raloxifene conferred a greater benefit (in QALYs) from prevention of invasive breast cancer than from fracture prevention. Results were most sensitive to the population's underlying risk of fracture and breast cancer, assumed efficacy and costs of treatment, and the discount rate.ConclusionFor 55 and 60 year old women with osteopenia, treatment with raloxifene compares favorably to interventions accepted as cost-effective.
| S-EPMC1866224 | biostudies-literature
Project description:Osteoporosis is a multifactorial and polygenic disease caused by an imbalance between osteoclastogenesis and osteoblastogenesis, leading to a decrease in bone mineral density and the occurrence of disorders in the microarchitecture and metabolism of bone tissue. In postmenopausal women, there is a significant decrease in the production of estrogens, which play a key role in maintaining proper bone mineral density. Estrogens have an inhibitory effect on the development and activity of osteoclasts by reducing the synthesis of pro-resorption cytokines and stimulating the expression of osteoprotegerin (OPG). Osteoprotegerin is a cytokine that prevents bone loss by inhibiting the process of osteoclastogenesis, reducing bone resorption. The aim of our study was to determine the influence of the rs3102735 (-163A>G), rs3134070 (-245T>G), rs207361 (-950T>C), rs7844539 (6890A>C), and rs2073618 (1181G>C) polymorphisms of the OPG gene on the risk of osteoporosis and osteopenia in postmenopausal Polish women. The study included 802 unrelated women (osteoporosis: n = 317, osteopenia: n = 110, controls: n = 375) at postmenopausal age (54.7 ± 8.6 years). Genetic analysis was performed using real-time PCR. BMD values as well as clinical and bone parameters with the tested polymorphisms were analyzed among the study population. Analysis of the PPARG rs1801282 variants did not show any association with the risk of osteoporosis and osteopenia. However, for the OPG rs207361 polymorphism, we observed a statistically significant association with the risk of osteoporosis, suggesting that the OPG rs207361 variant may be one of the genetic markers associated with the pathogenesis of osteoporosis.
| S-EPMC10740651 | biostudies-literature