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Osteoporosis: HELP
Articles by Sylvie Giroux
Based on 5 articles published since 2008
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Between 2008 and 2019, S. Giroux wrote the following 5 articles about Osteoporosis.
 
+ Citations + Abstracts
1 Article Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium. 2014

Moayyeri, Alireza / Hsu, Yi-Hsiang / Karasik, David / Estrada, Karol / Xiao, Su-Mei / Nielson, Carrie / Srikanth, Priya / Giroux, Sylvie / Wilson, Scott G / Zheng, Hou-Feng / Smith, Albert V / Pye, Stephen R / Leo, Paul J / Teumer, Alexander / Hwang, Joo-Yeon / Ohlsson, Claes / McGuigan, Fiona / Minster, Ryan L / Hayward, Caroline / Olmos, José M / Lyytikäinen, Leo-Pekka / Lewis, Joshua R / Swart, Karin M A / Masi, Laura / Oldmeadow, Chris / Holliday, Elizabeth G / Cheng, Sulin / van Schoor, Natasja M / Harvey, Nicholas C / Kruk, Marcin / del Greco M, Fabiola / Igl, Wilmar / Trummer, Olivia / Grigoriou, Efi / Luben, Robert / Liu, Ching-Ti / Zhou, Yanhua / Oei, Ling / Medina-Gomez, Carolina / Zmuda, Joseph / Tranah, Greg / Brown, Suzanne J / Williams, Frances M / Soranzo, Nicole / Jakobsdottir, Johanna / Siggeirsdottir, Kristin / Holliday, Kate L / Hannemann, Anke / Go, Min Jin / Garcia, Melissa / Polasek, Ozren / Laaksonen, Marika / Zhu, Kun / Enneman, Anke W / McEvoy, Mark / Peel, Roseanne / Sham, Pak Chung / Jaworski, Maciej / Johansson, Åsa / Hicks, Andrew A / Pludowski, Pawel / Scott, Rodney / Dhonukshe-Rutten, Rosalie A M / van der Velde, Nathalie / Kähönen, Mika / Viikari, Jorma S / Sievänen, Harri / Raitakari, Olli T / González-Macías, Jesús / Hernández, Jose L / Mellström, Dan / Ljunggren, Osten / Cho, Yoon Shin / Völker, Uwe / Nauck, Matthias / Homuth, Georg / Völzke, Henry / Haring, Robin / Brown, Matthew A / McCloskey, Eugene / Nicholson, Geoffrey C / Eastell, Richard / Eisman, John A / Jones, Graeme / Reid, Ian R / Dennison, Elaine M / Wark, John / Boonen, Steven / Vanderschueren, Dirk / Wu, Frederick C W / Aspelund, Thor / Richards, J Brent / Bauer, Doug / Hofman, Albert / Khaw, Kay-Tee / Dedoussis, George / Obermayer-Pietsch, Barbara / Gyllensten, Ulf / Pramstaller, Peter P / Lorenc, Roman S / Cooper, Cyrus / Kung, Annie Wai Chee / Lips, Paul / Alen, Markku / Attia, John / Brandi, Maria Luisa / de Groot, Lisette C P G M / Lehtimäki, Terho / Riancho, José A / Campbell, Harry / Liu, Yongmei / Harris, Tamara B / Akesson, Kristina / Karlsson, Magnus / Lee, Jong-Young / Wallaschofski, Henri / Duncan, Emma L / O'Neill, Terence W / Gudnason, Vilmundur / Spector, Timothy D / Rousseau, François / Orwoll, Eric / Cummings, Steven R / Wareham, Nick J / Rivadeneira, Fernando / Uitterlinden, Andre G / Prince, Richard L / Kiel, Douglas P / Reeve, Jonathan / Kaptoge, Stephen K. ·Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. ·Hum Mol Genet · Pubmed #24430505.

ABSTRACT: Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

2 Article Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. 2012

Estrada, Karol / Styrkarsdottir, Unnur / Evangelou, Evangelos / Hsu, Yi-Hsiang / Duncan, Emma L / Ntzani, Evangelia E / Oei, Ling / Albagha, Omar M E / Amin, Najaf / Kemp, John P / Koller, Daniel L / Li, Guo / Liu, Ching-Ti / Minster, Ryan L / Moayyeri, Alireza / Vandenput, Liesbeth / Willner, Dana / Xiao, Su-Mei / Yerges-Armstrong, Laura M / Zheng, Hou-Feng / Alonso, Nerea / Eriksson, Joel / Kammerer, Candace M / Kaptoge, Stephen K / Leo, Paul J / Thorleifsson, Gudmar / Wilson, Scott G / Wilson, James F / Aalto, Ville / Alen, Markku / Aragaki, Aaron K / Aspelund, Thor / Center, Jacqueline R / Dailiana, Zoe / Duggan, David J / Garcia, Melissa / Garcia-Giralt, Natàlia / Giroux, Sylvie / Hallmans, Göran / Hocking, Lynne J / Husted, Lise Bjerre / Jameson, Karen A / Khusainova, Rita / Kim, Ghi Su / Kooperberg, Charles / Koromila, Theodora / Kruk, Marcin / Laaksonen, Marika / Lacroix, Andrea Z / Lee, Seung Hun / Leung, Ping C / Lewis, Joshua R / Masi, Laura / Mencej-Bedrac, Simona / Nguyen, Tuan V / Nogues, Xavier / Patel, Millan S / Prezelj, Janez / Rose, Lynda M / Scollen, Serena / Siggeirsdottir, Kristin / Smith, Albert V / Svensson, Olle / Trompet, Stella / Trummer, Olivia / van Schoor, Natasja M / Woo, Jean / Zhu, Kun / Balcells, Susana / Brandi, Maria Luisa / Buckley, Brendan M / Cheng, Sulin / Christiansen, Claus / Cooper, Cyrus / Dedoussis, George / Ford, Ian / Frost, Morten / Goltzman, David / González-Macías, Jesús / Kähönen, Mika / Karlsson, Magnus / Khusnutdinova, Elza / Koh, Jung-Min / Kollia, Panagoula / Langdahl, Bente Lomholt / Leslie, William D / Lips, Paul / Ljunggren, Östen / Lorenc, Roman S / Marc, Janja / Mellström, Dan / Obermayer-Pietsch, Barbara / Olmos, José M / Pettersson-Kymmer, Ulrika / Reid, David M / Riancho, José A / Ridker, Paul M / Rousseau, François / Slagboom, P Eline / Tang, Nelson L S / Urreizti, Roser / Van Hul, Wim / Viikari, Jorma / Zarrabeitia, María T / Aulchenko, Yurii S / Castano-Betancourt, Martha / Grundberg, Elin / Herrera, Lizbeth / Ingvarsson, Thorvaldur / Johannsdottir, Hrefna / Kwan, Tony / Li, Rui / Luben, Robert / Medina-Gómez, Carolina / Palsson, Stefan Th / Reppe, Sjur / Rotter, Jerome I / Sigurdsson, Gunnar / van Meurs, Joyce B J / Verlaan, Dominique / Williams, Frances M K / Wood, Andrew R / Zhou, Yanhua / Gautvik, Kaare M / Pastinen, Tomi / Raychaudhuri, Soumya / Cauley, Jane A / Chasman, Daniel I / Clark, Graeme R / Cummings, Steven R / Danoy, Patrick / Dennison, Elaine M / Eastell, Richard / Eisman, John A / Gudnason, Vilmundur / Hofman, Albert / Jackson, Rebecca D / Jones, Graeme / Jukema, J Wouter / Khaw, Kay-Tee / Lehtimäki, Terho / Liu, Yongmei / Lorentzon, Mattias / McCloskey, Eugene / Mitchell, Braxton D / Nandakumar, Kannabiran / Nicholson, Geoffrey C / Oostra, Ben A / Peacock, Munro / Pols, Huibert A P / Prince, Richard L / Raitakari, Olli / Reid, Ian R / Robbins, John / Sambrook, Philip N / Sham, Pak Chung / Shuldiner, Alan R / Tylavsky, Frances A / van Duijn, Cornelia M / Wareham, Nick J / Cupples, L Adrienne / Econs, Michael J / Evans, David M / Harris, Tamara B / Kung, Annie Wai Chee / Psaty, Bruce M / Reeve, Jonathan / Spector, Timothy D / Streeten, Elizabeth A / Zillikens, M Carola / Thorsteinsdottir, Unnur / Ohlsson, Claes / Karasik, David / Richards, J Brent / Brown, Matthew A / Stefansson, Kari / Uitterlinden, André G / Ralston, Stuart H / Ioannidis, John P A / Kiel, Douglas P / Rivadeneira, Fernando. ·Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. ·Nat Genet · Pubmed #22504420.

ABSTRACT: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

3 Article Inositol polyphosphate 4-phosphatase B as a regulator of bone mass in mice and humans. 2011

Ferron, Mathieu / Boudiffa, Maya / Arsenault, Michel / Rached, Mohamed / Pata, Monica / Giroux, Sylvie / Elfassihi, Latifa / Kisseleva, Marina / Majerus, Philip W / Rousseau, François / Vacher, Jean. ·Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada. ·Cell Metab · Pubmed #21982707.

ABSTRACT: Osteoporosis is a multifactorial genetic disease characterized by reduction of bone mass due to dysregulation of osteoclast differentiation or maturation. Herein, we identified a regulator of osteoclastogenesis, the murine homolog of inositol polyphosphate 4-phosphatase type IIα (Inpp4bα). Expression of Inpp4bα is detected from early osteoclast differentiation to activation stage. Targeted expression of native Inpp4bα ex vivo repressed whereas phosphatase-inactive Inpp4bα stimulated osteoclast differentiation. Inpp4bα acts on intracellular calcium level that modulates NFATc1 nuclear translocation and activation. In vivo mice deficient in Inpp4b displayed increased osteoclast differentiation rate and potential resulting in decreased bone mass and osteoporosis. Importantly, INPP4B in human was identified as a susceptibility locus for osteoporosis. This study defined Inpp4b as a major modulator of the osteoclast differentiation and as a gene linked to variability of bone mineral density in mice and humans.

4 Article Association with replication between estrogen-related receptor gamma (ESRRgamma) polymorphisms and bone phenotypes in women of European ancestry. 2010

Elfassihi, Latifa / Giroux, Sylvie / Bureau, Alexandre / Laflamme, Nathalie / Cole, David Ec / Rousseau, François. ·Centre de Recherche de l'Hôpital St-François d'Assise du Centre Hospitalier Universitaire de Québec, Quebec, Canada. ·J Bone Miner Res · Pubmed #19821770.

ABSTRACT: Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor gamma (ESRRgamma) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRRgamma sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20 kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRRgamma in the determination of bone density in women.

5 Article Replication of associations between LRP5 and ESRRA variants and bone density in premenopausal women. 2008

Giroux, S / Elfassihi, L / Cole, D E C / Rousseau, F. ·Centre de Recherche de l'Hôpital, St-François d'Assise, Centre Hospitalier Universitaire de Québec, Quebec, Canada. Sylvie.giroux@crsfa.ulaval.ca ·Osteoporos Int · Pubmed #18418639.

ABSTRACT: INTRODUCTION: We sought to validate associations previously reported between LRP5 V667M polymorphism and lumbar spine (LS, p = 0.013) and femoral neck (FN, p = 0.0002) bone mineral density (BMD), and between ESRRA 23 base pair repeat polymorphism and LS BMD (p = 0.0036) in a sample of premenopausal Caucasian women using an independent sample. METHODS: For the replication sample, we recruited 673 premenopausal women from the Toronto metropolitan area. All women were Caucasian and had BMD measured. LRP5 V667M was genotyped by allele-specific PCR and ESRRA repeats by sizing of PCR products on agarose gels. RESULTS: We reproduced the same association as we reported previously between LRP5 V667M and LS BMD (p = 0.015) but not with FN BMD (p = 0.254). The combined data from the two populations indicate an effect size of 0.28SD for LS BMD (p = 0.00048) and an effect size of 0.26 SD for FN BMD (p = 0.00037). In contrast, the association we reported earlier between ESRRA repeats and LS BMD was not replicated in the sample from Toronto (p = 0.645). CONCLUSIONS: The association between LRP5 V667M and LS BMD is confirmed but not that between ESRRA repeats and LS BMD. This result indicates that it is imperative to validate any positive association in an independent sample.