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      Association between vitamin D receptor BsmI, FokI, and Cdx2 polymorphisms and osteoporosis risk: an updated meta-analysis

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          Abstract

          Background: Many studies have reported the association between vitamin D receptor ( VDR) polymorphism and osteoporosis risk. However, their results were conflicting. Six previous meta-analyses have been published to analyze VDR BsmI, FokI, and Cdx2 polymorphisms on osteoporosis risk. However, they did not evaluate the reliability of statistically significant associations. Furthermore, a lot of new articles have been published on these themes, and therefore an updated meta-analysis was performed to further explore these issues.

          Objectives: To explore the association between VDR BsmI, FokI, and Cdx2 polymorphisms polymorphisms and osteoporosis risk.

          Methods: The odds ratios (ORs) and 95% confidence intervals (95% CIs) were pooled to evaluate the association between VDR BsmI, FokI, and Cdx2 polymorphisms and osteoporosis risk. To evaluate the credibility of statistically significant associations, we applied the false-positive report probabilities (FPRPs) test and the Venice criteria.

          Results: Overall, statistically significantly increased osteoporosis risk was found in Indians and women for VDR FokI polymorphism. Statistically significantly decreased osteoporosis risk was found in West Asians for VDR BsmI polymorphism. However, when we performed a sensitivity analysis after excluding low quality and Hardy–Weinberg Disequilibrium (HWD) studies, significantly decreased osteoporosis risk was only found in overall population for VDR BsmI polymorphism. Further, less-credible positive results were identified when we evaluated the credibility of positive results.

          Conclusion: These positive findings should be interpreted with caution and indicate that significant association may most likely result from less-credible, rather than from true associations or biological factors on the VDR BsmI and FokI polymorphisms with osteoporosis risk .

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          Most cited references71

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          Osteoporosis: now and the future.

          Osteoporosis is a common disease characterised by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. With an ageing population, the medical and socioeconomic effect of osteoporosis, particularly postmenopausal osteoporosis, will increase further. A detailed knowledge of bone biology with molecular insights into the communication between bone-forming osteoblasts and bone-resorbing osteoclasts and the orchestrating signalling network has led to the identification of novel therapeutic targets. Novel treatment strategies have been developed that aim to inhibit excessive bone resorption and increase bone formation. The most promising novel treatments include: denosumab, a monoclonal antibody for receptor activator of NF-κB ligand, a key osteoclast cytokine; odanacatib, a specific inhibitor of the osteoclast protease cathepsin K; and antibodies against the proteins sclerostin and dickkopf-1, two endogenous inhibitors of bone formation. This overview discusses these novel therapies and explains their underlying physiology. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Genetics and biology of vitamin D receptor polymorphisms.

            The vitamin D endocrine system is involved in a wide variety of biological processes including bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation. Variations in this endocrine system have, thus, been linked to several common diseases, including osteoarthritis (OA), diabetes, cancer, cardiovascular disease, and tuberculosis. Evidence to support this pleiotropic character of vitamin D has included epidemiological studies on circulating vitamin D hormone levels, but also genetic epidemiological studies. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and have therefore gained much interest. DNA sequence variations, which occur frequently in the population, are referred to as "polymorphisms" and can have modest and subtle but true biological effects. Their abundance in the human genome as well as their high frequencies in the human population have made them targets to explain variation in risk of common diseases. Recent studies have indicated many polymorphisms to exist in the vitamin D receptor (VDR) gene, but the influence of VDR gene polymorphisms on VDR protein function and signaling is largely unknown. So far, three adjacent restriction fragment length polymorphisms for BsmI, ApaI, and TaqI, respectively, at the 3' end of the VDR gene have been the most frequently studied. Because these polymorphisms are probably nonfunctional, linkage disequilibrium with one or more truly functional polymorphisms elsewhere in the VDR gene is assumed to explain the associations observed. Research is therefore focussed on documenting additional polymorphisms across the VDR gene to verify this hypothesis and on trying to understand the functional consequences of the variations. Substantial progress has been made that will deepen our understanding of variability in the vitamin D endocrine system and might find applications in risk assessment of disease and in predicting response-to-treatment.
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              Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment.

              Large segments of the population at risk for osteoporosis and fracture have not been evaluated, and the usefulness of peripheral measurements for short-term prediction of fracture risk is uncertain. To describe the occurrence of low bone mineral density (BMD) in postmenopausal women, its risk factors, and fracture incidence during short-term follow-up. The National Osteoporosis Risk Assessment, a longitudinal observational study initiated September 1997 to March 1999, with approximately 12 months of subsequent follow-up. A total of 200 160 ambulatory postmenopausal women aged 50 years or older with no previous osteoporosis diagnosis, derived from 4236 primary care practices in 34 states. Baseline BMD T scores, obtained from peripheral bone densitometry performed at the heel, finger, or forearm; risk factors for low BMD, derived from questionnaire responses; and clinical fracture rates at 12-month follow-up. Using World Health Organization criteria, 39.6% had osteopenia (T score of -1 to -2.49) and 7.2% had osteoporosis (T score
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                Author and article information

                Contributors
                Journal
                Biosci Rep
                Biosci. Rep
                bsr
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                31 July 2020
                15 July 2020
                : 40
                : 7
                : BSR20201200
                Affiliations
                [1 ]Changzhi Medical College, No. 161, Jiefangdong Street, Shanxi Province, Changzhi 046000, China
                [2 ]Department of Orthopaedics, Heping Hospital Affiliated to Changzhi Medical College, Shanxi, Changzhi 046000, China
                [3 ]Department of Science and Education, Heping Hospital Affiliated to Changzhi Medical College, Shanxi, Changzhi 046000, China
                Author notes
                Correspondence: Hong-Zhuo Li ( lihz0999@ 123456sina.com ) or Xiao-Feng He ( 393120823@ 123456qq.com )
                Author information
                http://orcid.org/0000-0002-0039-5247
                http://orcid.org/0000-0003-2870-888X
                Article
                BSR20201200
                10.1042/BSR20201200
                7364509
                32627819
                ee7234f2-ee8f-4d3e-bf44-06ebc3cd267d
                © 2020 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 14 April 2020
                : 27 June 2020
                : 30 June 2020
                : 06 July 2020
                Page count
                Pages: 19
                Categories
                Molecular Bases of Health & Disease
                Mutation
                Molecular Interactions
                Research Articles

                Life sciences
                meta-analysis,osteoporosis,polymorphism,risk,vdr
                Life sciences
                meta-analysis, osteoporosis, polymorphism, risk, vdr

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