{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:15:48Z","timestamp":1773800148267,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2011,3,30]],"date-time":"2011-03-30T00:00:00Z","timestamp":1301443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Genome-wide gene expressions in bone biopsies from patients with postmenopausal osteoporosis and healthy controls were profiled, to identify osteoporosis candidate genes. All osteoporotic patients (n\u2009=\u200927) in an unbiased cohort of Norwegian women presented with bone mineral density (BMD) T-scores of less than \u22122.5 SD and one or more confirmed low-energy fracture(s). A validation group (n\u2009=\u200918) had clinical and laboratory parameters intermediate to the control (n\u2009=\u200939) and osteoporosis groups. RNA from iliac crest bone biopsies were analyzed by Affymetrix microarrays and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Differentially expressed genes in osteoporosis versus control groups were identified using the Bayesian ANOVA for microarrays (BAMarray) method, whereas the R-package Limma (Linear Models for Microarray Data) was used to determine whether these transcripts were explained by disease, age, body mass index (BMI), or combinations thereof. Laboratory tests showed normal ranges for the cohort. A total of 609 transcripts were differentially expressed in osteoporotic patients relative to controls; 256 transcripts were confirmed for disease when controlling for age or BMI. Most of the osteoporosis susceptibility genes (80%) also were confirmed to be regulated in the same direction in the validation group. Furthermore, 217 of 256 transcripts were correlated with BMD (adjusted for age and BMI) at various skeletal sites (|r|\u2009&amp;gt;\u20090.2, p\u2009&amp;lt;\u2009.05). Among the most distinctly expressed genes were Wnt antagonists DKK1 and SOST, the transcription factor SOX4, and the bone matrix proteins MMP13 and MEPE, all reduced in osteoporosis versus control groups. Our results identify potential osteoporosis susceptibility candidate genes adjusted for confounding factors (ie, age and BMI) with or without a significant correlation with BMD. \u00a9 2011 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.396","type":"journal-article","created":{"date-parts":[[2011,3,30]],"date-time":"2011-03-30T16:56:37Z","timestamp":1301504197000},"page":"1793-1801","source":"Crossref","is-referenced-by-count":56,"title":["Molecular disease map of bone characterizing the postmenopausal osteoporosis phenotype"],"prefix":"10.1093","volume":"26","author":[{"given":"Rune","family":"Jemtland","sequence":"first","affiliation":[{"name":"Section of Endocrinology, Department of Medicine, Rikshospitalet University Hospital, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marit","family":"Holden","sequence":"additional","affiliation":[{"name":"Norwegian Computing Center, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sjur","family":"Reppe","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Oslo University Hospital, Ullevaal, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole K","family":"Olstad","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Oslo University Hospital, Ullevaal, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Finn P","family":"Reinholt","sequence":"additional","affiliation":[{"name":"Institute for Pathology, University of Oslo, and Division of Pathology, Rikshospitalet University Hospital, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vigdis T","family":"Gautvik","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilde","family":"Refvem","sequence":"additional","affiliation":[{"name":"Department of Medicine, Lovisenberg Diaconal Hospital, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnoldo","family":"Frigessi","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway"},{"name":"Norwegian Computing Center, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Houston","sequence":"additional","affiliation":[{"name":"Immunodiagnostics Systems Ltd., Newcastle, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaare M","family":"Gautvik","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Lovisenberg Diaconal Hospital, Oslo, Norway"},{"name":"Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway"},{"name":"Department of Clinical Chemistry, Oslo University Hospital, Ullevaal, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,3,30]]},"reference":[{"key":"2024020318015683300_bib1","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/S0140-6736(02)08657-9","article-title":"Epidemiology and outcomes of osteoporotic fractures","volume":"359","author":"Cummings","year":"2002","journal-title":"Lancet."},{"key":"2024020318015683300_bib2","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0140-6736(02)08761-5","article-title":"Diagnosis of osteoporosis and assessment of fracture risk","volume":"359","author":"Kanis","year":"2002","journal-title":"Lancet."},{"key":"2024020318015683300_bib3","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/gm84","article-title":"How genomics has informed our understanding of the pathogenesis of osteoporosis","volume":"1","author":"Johnson","year":"2009","journal-title":"Genome Med."},{"key":"2024020318015683300_bib4","first-page":"26","article-title":"Genetic and environmental determinants of osteoporosis","volume":"7","author":"Kung","year":"2007","journal-title":"J Musculoskelet Neuronal Interact."},{"key":"2024020318015683300_bib5","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s001980050099","article-title":"Family history and risk of osteoporotic fracture. Study of Osteoporotic Fractures Research Group","volume":"8","author":"Fox","year":"1998","journal-title":"Osteoporos Int."},{"key":"2024020318015683300_bib6","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1136\/bmj.307.6912.1111","article-title":"Prediction of osteoporotic fractures by postural instability and bone density","volume":"307","author":"Nguyen","year":"1993","journal-title":"BMJ."},{"key":"2024020318015683300_bib7","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1172\/JCI107476","article-title":"Genetic factors in determining bone mass","volume":"52","author":"Smith","year":"1973","journal-title":"J Clin Invest."},{"key":"2024020318015683300_bib8","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1172\/JCI113125","article-title":"Genetic determinants of bone mass in adults. A twin study","volume":"80","author":"Pocock","year":"1987","journal-title":"J Clin Invest."},{"key":"2024020318015683300_bib9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11914-005-0019-5","article-title":"Genetic epidemiology of osteoporosis: past, present, and future","volume":"3","author":"Zmuda","year":"2005","journal-title":"Curr Osteoporos Rep."},{"key":"2024020318015683300_bib10","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1101\/gad.1449506","article-title":"Genetic regulation of bone mass and susceptibility to osteoporosis","volume":"20","author":"Ralston","year":"2006","journal-title":"Genes Dev."},{"key":"2024020318015683300_bib11","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1359\/jbmr.1999.14.12.1993","article-title":"Suggestive linkage of the parathyroid receptor type 1 to osteoporosis","volume":"14","author":"Duncan","year":"1999","journal-title":"J Bone Miner Res."},{"key":"2024020318015683300_bib12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1385\/ENDO:17:1:67","article-title":"A strategy for identifying osteoporosis risk genes","volume":"17","author":"Rowe","year":"2002","journal-title":"Endocrine."},{"key":"2024020318015683300_bib13","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1056\/NEJMoa0801197","article-title":"Multiple Genetic Loci for Bone Mineral Density and Fractures","volume":"358","author":"Styrkarsdottir","year":"2008","journal-title":"N Engl J Med."},{"key":"2024020318015683300_bib14","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/ng.284","article-title":"New sequence variants associated with bone mineral density","volume":"41","author":"Styrkarsdottir","year":"2009","journal-title":"Nat Genet."},{"key":"2024020318015683300_bib15","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1056\/NEJMe0803046","article-title":"Bona fide genetic associations with bone mineral density","volume":"358","author":"Hirschhorn","year":"2008","journal-title":"N Engl J Med."},{"key":"2024020318015683300_bib16","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1016\/S0140-6736(08)60600-5","article-title":"Snipping away at osteoporosis susceptibility","volume":"371","author":"Zmuda","year":"2008","journal-title":"Lancet."},{"key":"2024020318015683300_bib17","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/ng1096-203","article-title":"Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene","volume":"14","author":"Grant","year":"1996","journal-title":"Nat Genet."},{"key":"2024020318015683300_bib18","doi-asserted-by":"crossref","first-page":"427S","DOI":"10.1093\/ajcn\/83.2.427S","article-title":"Nutritional modulators of bone remodeling during aging","volume":"83","author":"Mundy","year":"2006","journal-title":"Am J Clin Nutr."},{"key":"2024020318015683300_bib19","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1210\/jcem.87.6.8621","article-title":"Genetic control of susceptibility to osteoporosis","volume":"87","author":"Ralston","year":"2002","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318015683300_bib20","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/S0140-6736(08)60599-1","article-title":"Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study","volume":"371","author":"Richards","year":"2008","journal-title":"Lancet."},{"key":"2024020318015683300_bib21","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.bone.2009.11.007","article-title":"Eight genes are highly associated with BMD variation in postmenopausal Caucasian women","volume":"46","author":"Reppe","year":"2010","journal-title":"Bone."},{"key":"2024020318015683300_bib22","first-page":"7","article-title":"BAMarray\u2122: Java software for Bayesian analysis of variance for microarray data","author":"Ishwaran","year":"2006","journal-title":"BMC Bioinformatics."},{"key":"2024020318015683300_bib23","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1198\/016214505000000051","article-title":"Spike and slab gene selection for multigroup microarray data., 100 ed","volume":"100","author":"Ishwaran","year":"2005","journal-title":"J Am Stat Assoc."},{"key":"2024020318015683300_bib24","doi-asserted-by":"crossref","DOI":"10.2202\/1544-6115.1027","article-title":"Linear models and empirical Bayes methods for assessing differential expression in microarray experiments","volume":"3","author":"Smyth","year":"2004","journal-title":"Stat Appl Genet Mol Biol."},{"key":"2024020318015683300_bib25","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/0-387-29362-0_23","volume-title":"Bioinformatics and Computational Biology Solutions using R and Bioconductor","author":"Smyth","year":"2005"},{"key":"2024020318015683300_bib26","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1007\/s10654-004-2173-y","article-title":"Risk of low-energy hip, wrist, and upper arm fractures among current and previous users of hormone replacement therapy: The Danish Nurse Cohort Study","volume":"19","author":"Hundrup","year":"2004","journal-title":"Eur J Epidemiol."},{"key":"2024020318015683300_bib27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/gepi.1040","article-title":"Relevance of the genes for bone mass variation to susceptibility to osteoporotic fractures and its implications to gene search for complex human diseases","volume":"22","author":"Deng","year":"2002","journal-title":"Genet Epidemiol."},{"key":"2024020318015683300_bib28","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1007\/s00198-007-0343-y","article-title":"The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women","volume":"18","author":"Kanis","year":"2007","journal-title":"Osteoporos Int."},{"key":"2024020318015683300_bib29","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.beem.2008.08.007","article-title":"Human genetics of osteoporosis","volume":"22","author":"Ferrari","year":"2008","journal-title":"Best Pract Res Clin Endocrinol Metab."},{"key":"2024020318015683300_bib30","doi-asserted-by":"crossref","first-page":"528","DOI":"10.7326\/0003-4819-151-8-200910200-00006","article-title":"Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture","volume":"151","author":"Richards","year":"2009","journal-title":"Ann Intern Med."},{"key":"2024020318015683300_bib31","doi-asserted-by":"crossref","first-page":"29011","DOI":"10.1074\/jbc.M501164200","article-title":"A novel pathophysiological mechanism for osteoporosis suggested by an in vivo gene expression study of circulating monocytes","volume":"280","author":"Liu","year":"2005","journal-title":"J Biol Chem."},{"key":"2024020318015683300_bib32","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1172\/JCI28551","article-title":"Regulation of bone mass by Wnt signaling","volume":"116","author":"Krishnan","year":"2006","journal-title":"J Clin Invest."},{"key":"2024020318015683300_bib33","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1210\/en.2007-0270","article-title":"Targeting the Wnt\/beta-catenin pathway to regulate bone formation in the adult skeleton","volume":"148","author":"Baron","year":"2007","journal-title":"Endocrinology."},{"issue":"(Suppl1)","key":"2024020318015683300_bib34","article-title":"Osteocyte Apoptosis and Expression of Sclerostin in Postmenopausal Women with Fragility Hip Fracture","volume":"34","author":"Truong","year":"2009","journal-title":"J Bone Miner Res."},{"key":"2024020318015683300_bib35","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat Protoc."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.396","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/8\/1793\/56559413\/396_ftp.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/8\/1793\/56559413\/396_ftp.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:04:59Z","timestamp":1710342299000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/26\/8\/1793-1801\/7598161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,30]]},"references-count":35,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2011,3,30]]},"published-print":{"date-parts":[[2011,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.396","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,8,1]]},"published":{"date-parts":[[2011,3,30]]}}}