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      Pharmacogenomics Study for Raloxifene in Postmenopausal Female with Osteoporosis

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          Abstract

          Osteoporosis is characterized by decreased bone mineral density and increased risk of fracture. Raloxifene is one of the treatments of osteoporosis. However, the responses were variable among patients. Previous studies revealed that the genetic variants are involved in the regulation of treatment outcomes. To date, studies that evaluate the influence of genes across all genome on the raloxifene treatment response are still limited. In this study, a total of 41 postmenopausal osteoporosis patients under regular raloxifene treatment were included. Gene-based analysis using MAGMA was applied to investigate the genetic association with the bone mineral density response to raloxifene at the lumbar spine or femoral neck site. Results from gene-based analysis indicated several genes ( GHRHR, ABHD8, and TMPRSS6) related to the responses of raloxifene. Besides, the pathways of iron ion homeostasis, osteoblast differentiation, and platelet morphogenesis were enriched which implies that these pathways might be relatively susceptible to raloxifene treatment outcome. Our study provided a novel insight into the response to raloxifene.

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          Most cited references 23

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          The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine.

          The goal of our study was to estimate the prevalence of osteoporosis and low bone mass based on bone mineral density (BMD) at the femoral neck and the lumbar spine in adults 50 years and older in the United States (US). We applied prevalence estimates of osteoporosis or low bone mass at the femoral neck or lumbar spine (adjusted by age, sex, and race/ethnicity to the 2010 Census) for the noninstitutionalized population aged 50 years and older from the National Health and Nutrition Examination Survey 2005-2010 to 2010 US Census population counts to determine the total number of older US residents with osteoporosis and low bone mass. There were more than 99 million adults aged 50 years and older in the US in 2010. Based on an overall 10.3% prevalence of osteoporosis, we estimated that in 2010, 10.2 million older adults had osteoporosis. The overall low bone mass prevalence was 43.9%, from which we estimated that 43.4 million older adults had low bone mass. We estimated that 7.7 million non-Hispanic white, 0.5 million non-Hispanic black, and 0.6 million Mexican American adults had osteoporosis, and another 33.8, 2.9, and 2.0 million had low bone mass, respectively. When combined, osteoporosis and low bone mass at the femoral neck or lumbar spine affected an estimated 53.6 million older US adults in 2010. Although most of the individuals with osteoporosis or low bone mass were non-Hispanic white women, a substantial number of men and women from other racial/ethnic groups also had osteoporotic BMD or low bone mass. © 2014 American Society for Bone and Mineral Research.
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            Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women.

            Long-term estrogen therapy can reduce the risk of osteoporotic fracture and cardiovascular disease in postmenopausal women. At present, however, these beneficial effects are not separable from undesirable stimulation of breast and endometrial tissues. We studied the effect of raloxifene, a nonsteroidal benzothiophene, on bone mineral density, serum lipid concentrations, and endometrial thickness in 601 postmenopausal women. The women were randomly assigned to receive 30, 60, or 150 mg of raloxifene or placebo daily for 24 months. The women receiving each dose of raloxifene had significant increases from base-line values in bone mineral density of the lumbar spine, hip, and total body, whereas those receiving placebo had decreases in bone mineral density. For example, at 24 months, the mean (+/-SE) difference in the change in bone mineral density between the women receiving 60 mg of raloxifene per day and those receiving placebo was 2.4+/-0.4 percent for the lumbar spine, 2.4+/-0.4 percent for the total hip, and 2.0+/-0.4 percent for the total body (P<0.001 for all comparisons). Serum concentrations of total cholesterol and low-density lipoprotein cholesterol decreased in all the raloxifene groups, whereas serum concentrations of high-density lipoprotein cholesterol and triglycerides did not change. Endometrial thickness was similar in the raloxifene and placebo groups at all times during the study. The proportion of women receiving raloxifene who reported hot flashes or vaginal bleeding was not different from that of the women receiving placebo. Daily therapy with raloxifene increases bone mineral density, lowers serum concentrations of total and low-density lipoprotein cholesterol, and does not stimulate the endometrium.
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              Osteoporosis: the evolution of a diagnosis.

              The global trend towards increased longevity has resulted in ageing populations and a rise in diseases or conditions that primarily affect older persons. One such condition is osteoporosis (fragile or porous bones), which causes an increased fracture risk. Vertebral and hip fractures lead to increased morbidity and mortality and result in enormous healthcare costs. Here, we review the evolution of the diagnosis of osteoporosis. In an attempt to separate patients with normal bones from those with osteoporosis and to define the osteoporosis diagnosis, multiple factors and characteristics have been considered. These include pathology and histology of the disease, the endocrine regulation of bone metabolism, bone mineral density (BMD), fracture type or trauma severity, risk models for fracture prediction, and thresholds for pharmacological intervention. The femoral neck BMD -2.5 SDs cut-off for the diagnosis of osteoporosis is arbitrarily chosen, and there is no evidence to support the notion that fracture location (except vertebral fractures) or severity is useful to discriminate osteoporotic from normal bones. Fracture risk models (including factors unrelated to bone) dissociate bone strength from the diagnosis, and treatment thresholds are often based on health-economic considerations rather than bone properties. Vertebral fractures are a primary feature of osteoporosis, characterized by decreased bone mass, strength and quality, and a high risk of another such fracture that can be considerably reduced by treatment. We believe that the 2001 definition of osteoporosis by the National Institutes of Health Consensus Development Panel on Osteoporosis is still valid and useful: 'Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture'.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis. Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2020
                31 August 2020
                : 2020
                Affiliations
                1Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
                2School of Medicine, National Yang-Ming University, Taipei, Taiwan
                3Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan
                4Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
                5Department of Pharmacy, University of Muhammadiyah Mataram, Mataram, Indonesia
                6Clinical Drug Development of Chinese Herbal Medicine, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
                7Graduate Institute of Injury Prevention and Control, College of Public Health, Taipei Medical University, Taipei 11042, Taiwan
                8Department of Neurosurgery, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan
                9Pain Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
                10Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
                Author notes

                Academic Editor: Wen-Jun Tu

                Article
                10.1155/2020/8855423
                7479487
                Copyright © 2020 Hsing-Fang Lu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funding
                Funded by: Ministry of Education
                Award ID: MOE DP2-107-21121-A-05
                Funded by: Ministry of Science and Technology, Taiwan
                Award ID: MOST 106-2923-B-038-002
                Award ID: MOST 105-2628-B-038-001-MY4
                Categories
                Research Article

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