The Experts below are selected from a list of 11379 Experts worldwide ranked by ideXlab platform
Eveline Boudin - One of the best experts on this subject based on the ideXlab platform.
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A look behind the scenes: the risk and pathogenesis of Primary Osteoporosis
Nature Reviews Rheumatology, 2015Co-Authors: Gretl Hendrickx, Eveline BoudinAbstract:This article discusses the many heritable and nonheritable factors contributing to Primary Osteoporosis, focusing on osteogenesis imperfecta, juvenile Osteoporosis and other monogenic disorders associated with increased bone fragility. Understanding these conditions not only illuminates the pathogenesis of Osteoporosis, but could also lead to the discovery of new therapeutic targets. The pathogenesis of Primary Osteoporosis is complex and influenced by both environmental and genetic factors Oxidative stress, apoptosis, sex-steroid deficiency and macroautophagy are age-related risk factors that contribute to the pathogenesis of Osteoporosis Lifestyle-related factors, such as inadequate intake of calcium and vitamin D, physical inactivity, smoking and excessive alcohol consumption are important risk factors for Osteoporosis Mutations in several genes can cause different monogenic disorders characterized by decreased bone mineral density and increased bone fragility The contribution of genetic factors to polygenic Osteoporosis is determined by the presence of variants in many genes, each with a small effect size Osteoporosis is a common disorder, affecting hundreds of millions of people worldwide, and characterized by decreased bone mineral density and increased fracture risk. Known nonheritable risk factors for Primary Osteoporosis include advanced age, sex-steroid deficiency and increased oxidative stress. Age is a nonmodifiable risk factor, but the influence of a person's lifestyle (diet and physical activity) on their bone structure and density is modifiable to some extent. Heritable factors influencing bone fragility can be monogenic or polygenic. Osteogenesis imperfecta, juvenile Osteoporosis and syndromes of decreased bone density are discussed as examples of monogenic disorders associated with bone fragility. So far, the factors associated with polygenic Osteoporosis have been investigated mainly in genome-wide association studies. However, epigenetic mechanisms also contribute to the heritability of polygenic Osteoporosis. Identification of these heritable and nonheritable risk factors has already led to the discovery of therapeutic targets for Osteoporosis, which emphasizes the importance of research into the pathogenetic mechanisms of Osteoporosis. Accordingly, this article discusses the many heritable and nonheritable factors that contribute to the pathogenesis of Primary Osteoporosis. Although Osteoporosis can also develop secondary to many other diseases or their treatment, a discussion of the factors that contribute only to secondary Osteoporosis is beyond the scope of this Review.
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A look behind the scenes: the risk and pathogenesis of Primary Osteoporosis
Nature reviews. Rheumatology, 2015Co-Authors: Gretl Hendrickx, Eveline Boudin, Wim Van HulAbstract:This article discusses the many heritable and nonheritable factors contributing to Primary Osteoporosis, focusing on osteogenesis imperfecta, juvenile Osteoporosis and other monogenic disorders associated with increased bone fragility. Understanding these conditions not only illuminates the pathogenesis of Osteoporosis, but could also lead to the discovery of new therapeutic targets.
Gretl Hendrickx - One of the best experts on this subject based on the ideXlab platform.
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A look behind the scenes: the risk and pathogenesis of Primary Osteoporosis
Nature Reviews Rheumatology, 2015Co-Authors: Gretl Hendrickx, Eveline BoudinAbstract:This article discusses the many heritable and nonheritable factors contributing to Primary Osteoporosis, focusing on osteogenesis imperfecta, juvenile Osteoporosis and other monogenic disorders associated with increased bone fragility. Understanding these conditions not only illuminates the pathogenesis of Osteoporosis, but could also lead to the discovery of new therapeutic targets. The pathogenesis of Primary Osteoporosis is complex and influenced by both environmental and genetic factors Oxidative stress, apoptosis, sex-steroid deficiency and macroautophagy are age-related risk factors that contribute to the pathogenesis of Osteoporosis Lifestyle-related factors, such as inadequate intake of calcium and vitamin D, physical inactivity, smoking and excessive alcohol consumption are important risk factors for Osteoporosis Mutations in several genes can cause different monogenic disorders characterized by decreased bone mineral density and increased bone fragility The contribution of genetic factors to polygenic Osteoporosis is determined by the presence of variants in many genes, each with a small effect size Osteoporosis is a common disorder, affecting hundreds of millions of people worldwide, and characterized by decreased bone mineral density and increased fracture risk. Known nonheritable risk factors for Primary Osteoporosis include advanced age, sex-steroid deficiency and increased oxidative stress. Age is a nonmodifiable risk factor, but the influence of a person's lifestyle (diet and physical activity) on their bone structure and density is modifiable to some extent. Heritable factors influencing bone fragility can be monogenic or polygenic. Osteogenesis imperfecta, juvenile Osteoporosis and syndromes of decreased bone density are discussed as examples of monogenic disorders associated with bone fragility. So far, the factors associated with polygenic Osteoporosis have been investigated mainly in genome-wide association studies. However, epigenetic mechanisms also contribute to the heritability of polygenic Osteoporosis. Identification of these heritable and nonheritable risk factors has already led to the discovery of therapeutic targets for Osteoporosis, which emphasizes the importance of research into the pathogenetic mechanisms of Osteoporosis. Accordingly, this article discusses the many heritable and nonheritable factors that contribute to the pathogenesis of Primary Osteoporosis. Although Osteoporosis can also develop secondary to many other diseases or their treatment, a discussion of the factors that contribute only to secondary Osteoporosis is beyond the scope of this Review.
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A look behind the scenes: the risk and pathogenesis of Primary Osteoporosis
Nature reviews. Rheumatology, 2015Co-Authors: Gretl Hendrickx, Eveline Boudin, Wim Van HulAbstract:This article discusses the many heritable and nonheritable factors contributing to Primary Osteoporosis, focusing on osteogenesis imperfecta, juvenile Osteoporosis and other monogenic disorders associated with increased bone fragility. Understanding these conditions not only illuminates the pathogenesis of Osteoporosis, but could also lead to the discovery of new therapeutic targets.
William G Cole - One of the best experts on this subject based on the ideXlab platform.
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rare variations in wnt3a and dkk1 may predispose carriers to Primary Osteoporosis
European Journal of Medical Genetics, 2012Co-Authors: Johanna Korvala, Marika Loija, Outi Makitie, Etienne Sochett, Harald Juppner, Dirk Schnabel, Stefano Mora, William G Cole, Leena Alakokko, Minna MannikkoAbstract:Childhood-onset Primary Osteoporosis is manifested as reduced bone mineral density, peripheral fractures and/or vertebral compression fractures. Until now, only mutations in LRP5 have been shown to cause the disorder. Candidate gene analyses were performed on 15 patients with Primary Osteoporosis and 80 healthy controls using CSGE and sequencing. The genes studied included DKK1, DKK2, WNT3A, WNT10B, AXIN1, SOST, TPH1 and 5-HTR1B. Two rare variants in WNT3A (c.152A > G, p.K51R) and DKK1 (c.359G > T, p.R120L) were identified in two patients and their affected family members, but not in control subjects, suggesting a significance for the skeletal phenotype. The in vitro studies of variants showed reduced signaling activity in p.K51R-Wnt3a, while no differences were observed between the WT and variant forms of DKK1. This study addresses the role of other components of the canonical Wnt signaling pathway besides LRP5 in Primary Osteoporosis, and putatively associates WNT3A and DKK1 variants with the disorder. Future functional studies are needed to elucidate the functional effects of the variants.
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mutations in lrp5 cause Primary Osteoporosis without features of oi by reducing wnt signaling activity
BMC Medical Genetics, 2012Co-Authors: Johanna Korvala, Outi Makitie, Etienne Sochett, Harald Juppner, Dirk Schnabel, Stefano Mora, Cynthia F Bartels, Matthew L Warman, Donald Deraska, William G ColeAbstract:Background Primary Osteoporosis is a rare childhood-onset skeletal condition whose pathogenesis has been largely unknown. We have previously shown that Primary Osteoporosis can be caused by heterozygous missense mutations in the Low-density lipoprotein receptor-related protein 5 (LRP5) gene, and the role of LRP5 is further investigated here.
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Mutations in LRP5 cause Primary Osteoporosis without features of OI by reducing Wnt signaling activity
BMC Medical Genetics, 2012Co-Authors: Johanna Korvala, Outi Makitie, Etienne Sochett, Harald Juppner, Dirk Schnabel, Stefano Mora, Cynthia F Bartels, Matthew L Warman, Donald Deraska, William G ColeAbstract:Background Primary Osteoporosis is a rare childhood-onset skeletal condition whose pathogenesis has been largely unknown. We have previously shown that Primary Osteoporosis can be caused by heterozygous missense mutations in the Low-density lipoprotein receptor-related protein 5 ( LRP5 ) gene, and the role of LRP5 is further investigated here. Methods LRP5 was analyzed in 18 otherwise healthy children and adolescents who had evidence of Osteoporosis (manifested as reduced bone mineral density i.e. BMD, recurrent peripheral fractures and/or vertebral compression fractures) but who lacked the clinical features of osteogenesis imperfecta (OI) or other known syndromes linked to low BMD. Also 51 controls were analyzed. Methods used in the genetic analyses included direct sequencing and multiplex ligation-dependent probe amplification (MLPA). In vitro studies were performed using luciferase assay and quantitative real-time polymerase chain reaction (qPCR) to examine the effect of two novel and three previously identified mutations on the activity of canonical Wnt signaling and on expression of tryptophan hydroxylase 1 ( Tph1 ) and 5-hydroxytryptamine ( 5-Htr1b ). Results Two novel LRP5 mutations (c.3446 T > A; p.L1149Q and c.3553 G > A; p.G1185R) were identified in two patients and their affected family members. In vitro analyses showed that one of these novel mutations together with two previously reported mutations (p.C913fs, p.R1036Q) significantly reduced the activity of the canonical Wnt signaling pathway. Such reductions may lead to decreased bone formation, and could explain the bone phenotype. Gut-derived Lrp5 has been shown to regulate serotonin synthesis by controlling the production of serotonin rate-limiting enzyme, Tph1. LRP5 mutations did not affect Tph1 expression, and only one mutant (p.L1149Q) reduced expression of serotonin receptor 5-Htr1b ( p < 0.002). Conclusions Our results provide additional information on the role of LRP5 mutations and their effects on the development of juvenile-onset Primary Osteoporosis, and hence the pathogenesis of the disorder. The mutations causing Primary Osteoporosis reduce the signaling activity of the canonical Wnt signaling pathway and may therefore result in decreased bone formation. The specific mechanism affecting signaling activity remains to be resolved in future studies.
Wim Van Hul - One of the best experts on this subject based on the ideXlab platform.
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A look behind the scenes: the risk and pathogenesis of Primary Osteoporosis
Nature reviews. Rheumatology, 2015Co-Authors: Gretl Hendrickx, Eveline Boudin, Wim Van HulAbstract:This article discusses the many heritable and nonheritable factors contributing to Primary Osteoporosis, focusing on osteogenesis imperfecta, juvenile Osteoporosis and other monogenic disorders associated with increased bone fragility. Understanding these conditions not only illuminates the pathogenesis of Osteoporosis, but could also lead to the discovery of new therapeutic targets.
Cui Xilong - One of the best experts on this subject based on the ideXlab platform.
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A systematic review of Qianggu capsule for treatment of Primary Osteoporosis
Chinese Journal of Osteoporosis, 2010Co-Authors: Cui XilongAbstract:Objective To systematically review the efficacy and safety of Qianggu capsule for treatment of Primary Osteoporosis. Methods Literatures related to Qianggu capsule for Osteoporosis treatment in the past 10 years was searched using computer searching system. Data was extracted according to the inclusion and exclusion standard. Meta-analysis was used to systematically review the efficacy and safety,including BMD, bone pain and complications. Results Five literatures were included. Using meta-analysis,it was found that BMD change had statistical difference ( P = 0. 02) before and after Qianggu capsule treatment. Bone pain alleviation had significant statistical difference ( P = 0. 001 ), comparing to traditional drugs. ConclusionCurrent clinical evidence indicates that Qianggu capsule is efficient for increasing BMD in Primary Osteoporosis and for alleviating bone pain. More high quality randomized control trials are needed for further evidence.