Dataset Information

Hypomethylation of Alu elements in post-menopausal women with osteoporosis.

ABSTRACT: A decrease in genomic methylation commonly occurs in aging cells; however, whether this epigenetic modification leads to age-related phenotypes has not been evaluated. Alu elements are the major interspersed repetitive DNA elements in humans that lose DNA methylation in aging individuals. Alu demethylation in blood cells starts at approximately 40 years of age, and the degree of Alu hypomethylation increases with age. Bone mass is lost with aging, particularly in menopausal women with lower body mass. Consequently, osteoporosis is commonly found in thin postmenopausal women. Here, we correlated the Alu methylation level of blood cells with bone density in 323 postmenopausal women. Alu hypomethylation was associated with advanced age and lower bone mass density, (P<0.05). The association between the Alu methylation level and bone mass was independent of age, body mass, and body fat, with an odds ratio [1] ?=?0.4316 (0.2087-0.8927). Individuals of the same age with osteopenia, osteoporosis, and a high body mass index have lower Alu methylation levels (P?=?0.0005, 0.003, and ?0.0001, respectively). Finally, when comparing individuals with the same age and body mass, Alu hypomethylation was observed in individuals with lower bone mass (P<0.0001). In conclusion, there are positive correlations between Alu hypomethylation in blood cells and several age-related phenotypes in bone and body fat. Therefore, reduced global methylation may play a role in the systemic senescence process. Further evaluation of Alu hypomethylation may clarify the epigenetic regulation of osteoporosis in post-menopausal women.

SUBMITTER: Jintaridth P

PROVIDER: S-EPMC3749148 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Hypomethylation of Alu elements in post-menopausal women with osteoporosis.

Jintaridth Pornrutsami P Tungtrongchitr Rungsunn R Preutthipan Sangchai S Mutirangura Apiwat A

PloS one 20130821 8

A decrease in genomic methylation commonly occurs in aging cells; however, whether this epigenetic modification leads to age-related phenotypes has not been evaluated. Alu elements are the major interspersed repetitive DNA elements in humans that lose DNA methylation in aging individuals. Alu demethylation in blood cells starts at approximately 40 years of age, and the degree of Alu hypomethylation increases with age. Bone mass is lost with aging, particularly in menopausal women with lower body ...[more]

PMID: 23990903

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Project description:BackgroundAdherence to anti-osteoporosis treatments is poor, exposing treated women to increased fracture risk. Determinants of poor adherence are poorly understood. The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance.MethodsThis was an observational, cross-sectional pharmacoepidemiological study with a randomly-selected sample of 420 GPs, 154 rheumatologists and 110 gynaecologists practicing in France. Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months. Investigators completed a questionnaire on clinical features, treatments and medical history, and on patient compliance. Patients completed a questionnaire on sociodemographic features, lifestyle, attitudes and knowledge about osteoporosis, treatment compliance, treatment satisfaction and quality of life. Treatment compliance was evaluated with the Morisky Medication-taking Adherence Scale. Variables collected in the questionnaires were evaluated for association with compliance using multivariate logistic regression analysis.Results785 women were evaluated. Physicians considered 95.4% of the sample to be compliant, but only 65.5% of women considered themselves compliant. The correlation between patient and physician perceptions of compliance was low (?: 0.11 [95% CI: 0.06 to 0.16]). Patient-rated compliance was highest for monthly bisphosphonates (79.7%) and lowest for hormone substitution therapy (50.0%). Six variables were associated with compliance: treatment administration frequency, perceptions of long-term treatment acceptability, perceptions of health consequences of osteoporosis, perceptions of knowledge about osteoporosis, exercise and mental quality of life.ConclusionCompliance to anti-osteoporosis treatments is poor. Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance.

Project description:Studies examining real-world effectiveness of osteoporosis therapies are beset by limitations due to confounding by indication. By evaluating longitudinal changes in fracture incidence, we demonstrated that osteoporosis therapies are effective in reducing fracture risk in real-world practice settings. INTRODUCTION:Osteoporosis therapies have been shown to reduce incidence of vertebral and non-vertebral fractures in placebo-controlled randomized clinical trials. However, information on the real-world effectiveness of these therapies is limited. METHODS:We examined fracture risk reduction in older, post-menopausal women treated with osteoporosis therapies. Using Medicare claims, we identified 1,278,296 women age ≥ 65 years treated with zoledronic acid, oral bisphosphonates, denosumab, teriparatide, or raloxifene. Fracture incidence rates before and after treatment initiation were described to understand patients' fracture risk profile, and fracture reduction effectiveness of each therapy was evaluated as a longitudinal change in incidence rates. RESULTS:Fracture incidence rates increased during the period leading up to treatment initiation and were highest in the 3-month period most proximal to treatment initiation. Fracture incidence rates following treatment initiation were significantly lower than before treatment initiation. Compared with the 12-month pre-index period, there were reductions in clinical vertebral fractures for denosumab (45%; 95% confidence interval [CI] 39-51%), zoledronic acid (50%; 95% CI 47-52%), oral bisphosphonates (24%; 95% CI 22-26%), and teriparatide (72%; 95% CI 69-75%) during the subsequent 12 months. Relative to the first 3 months after initiation, clinical vertebral fractures were reduced for denosumab (51%; 95% CI 42-59%), zoledronic acid (25%; 95% CI 17-32%), oral bisphosphonates (23%; 95% CI 20-26%), and teriparatide (64%; 95% CI 58-69%) during the subsequent 12 months. CONCLUSION:In summary, reductions in fracture incidence over time were observed in cohorts of patients treated with osteoporosis therapies.

Project description:We aimed to investigate the association between cadmium levels and the risk of osteopenia and osteoporosis in Korean post-menopausal women. There was a significant positive association between cadmium levels and the risk of osteopenia and osteoporosis, but further studies for dose response are required.PurposeCadmium exposure can exert detrimental effects on bone health, particularly in post-menopausal women. However, previous studies have failed to report an association in Korean post-menopausal women. We aimed to investigate the association between cadmium levels and the risk of osteopenia and osteoporosis in Korean post-menopausal women.MethodsIn total, 5432 participants from the 4th and 5th Korean National Health and Nutrition Examination Survey (KNHANES) were randomly sampled for measurements of heavy metal concentrations in the blood, bone mass density (BMD), and nutrient intake. We analyzed data for 1031 post-menopausal women ≥50 years of age. Blood cadmium levels were categorized into quartiles, and a multinomial logistic regression model was used for analysis.ResultsThere was a significant positive association between cadmium levels and the risk of osteopenia and osteoporosis, but the odds ratio (OR) at the 4th level was lower than that at the 3rd level (OR and 95% confidence interval (CI) for osteopenia: 2nd quartile: 1.24, 0.88-1.74; 3rd quartile: 3.22, 2.24-4.64; 4th quartile: 1.27, 0.87-1.85; P for trend <0.001; OR and 95% CI for osteoporosis: 2nd quartile: 1.54, 1.05-2.25; 3rd quartile: 3.63, 2.31-5.69; 4th quartile: 1.70, 1.03-2.81; P for trend <0.001). This trend was consistent in the sensitivity analysis.ConclusionOur findings suggest that there is an association between blood cadmium levels and the risk of osteopenia and osteoporosis in Korean post-menopausal women. However, further prospective studies are required to determine whether there is a dose-response relationship and address potential selection bias, especially in patients with femoral neck osteoporosis.

Project description:Background Muscle ageing contributes to both loss of functional autonomy and increased morbidity. Muscle atrophy accelerates after 50 years of age, but the mechanisms involved are complex and likely result from the alteration of a variety of interrelated functions. In order to better understand the molecular mechanisms underlying muscle chronological ageing in human, we have undertaken a top-down differential proteomic approach to identify novel biomarkers after the fifth decade of age. Results Muscle samples were compared between adult (56 years) and old (78 years) post-menopausal women. In addition to total muscle extracts, low-ionic strength extracts were investigated to remove high abundance myofibrillar proteins and improve the detection of low abundance proteins. Two-dimensional gel electrophoreses with overlapping IPGs were used to improve the separation of muscle proteins. Overall, 1919 protein spots were matched between all individuals, 95 were differentially expressed and identified by mass spectrometry, and they corresponded to 67 different proteins. Our results suggested important modifications in cytosolic, mitochondrial and lipid energy metabolism, which may relate to dysfunctions in old muscle force generation. A fraction of the differentially expressed proteins were linked to the sarcomere and cytoskeleton (myosin light-chains, troponin T, ankyrin repeat domain-containing protein-2, vinculin, four and a half LIM domain protein-3), which may account for alterations in contractile properties. In line with muscle contraction, we also identified proteins related to calcium signal transduction (calsequestrin-1, sarcalumenin, myozenin-1, annexins). Muscle ageing was further characterized by the differential regulation of several proteins implicated in cytoprotection (catalase, peroxiredoxins), ion homeostasis (carbonic anhydrases, selenium-binding protein 1) and detoxification (aldo-keto reductases, aldehyde dehydrogenases). Notably, many of the differentially expressed proteins were central for proteostasis, including heat shock proteins and proteins involved in proteolysis (valosin-containing protein, proteasome subunit beta type-4, mitochondrial elongation factor-Tu). Conclusions This study describes the most extensive proteomic analysis of muscle ageing in humans, and identified 34 new potential biomarkers. None of them were previously recognized as differentially expressed in old muscles, and each may represent a novel starting point to elucidate the mechanisms of muscle chronological ageing in humans.

Dataset Information

Hypomethylation of Alu elements in post-menopausal women with osteoporosis.

Publications

Hypomethylation of Alu elements in post-menopausal women with osteoporosis.

Similar Datasets

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