{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:39:12Z","timestamp":1770910752661,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Genes explaining the susceptibility to osteoporosis have not been fully elucidated. Our objective was to explore the association of polymorphisms capturing common variations of the lipoprotein receptor-related protein (<jats:italic>LRP<\/jats:italic>)<jats:italic>5<\/jats:italic>and<jats:italic>6<\/jats:italic>genes, encoding two Wnt receptors, with femoral neck bone mineral density (BMD) and osteoporotic fractures of the spine and the hip.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Cross-sectional, case\u2013control, and replication genetic association study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty-nine tagging and functional single nucleotide polymorphisms (SNPs) were analyzed in a group of 1043 postmenopausal women and 394 women with hip fractures. The results were replicated in a different group of 342 women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three SNPs of the<jats:italic>LRP6<\/jats:italic>gene were associated with BMD (nominal uncorrected<jats:italic>P<\/jats:italic>values &lt;0.05) in the discovery cohort. One showed a significant association after multiple test correction; two of them were also associated in the replication cohort, with a combined standardized mean difference of 0.51 (<jats:italic>P<\/jats:italic>=0.009) and 0.47 (<jats:italic>P<\/jats:italic>&lt;0.003) across rs11054704 and rs2302685 genotypes. In the discovery cohort, several<jats:italic>LRP5<\/jats:italic>SNPs were associated with vertebral fractures (odds ratio (OR) 0.67;<jats:italic>P<\/jats:italic>=0.01), with hip fractures (unadjusted ORs between 0.59 and 1.21;<jats:italic>P<\/jats:italic>=0.005\u20130.033, but not significant after multiple test adjustment or age adjustment), and with height and the projected femoral neck area, but not with BMD. Transcripts of<jats:italic>LRP5<\/jats:italic>and<jats:italic>LRP6<\/jats:italic>were similarly abundant in bone samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this study, we found common polymorphisms of<jats:italic>LRP5<\/jats:italic>associated with osteoporotic fractures, and polymorphisms of the<jats:italic>LRP6<\/jats:italic>gene associated with BMD, thus suggesting them as likely candidates to contribute to the explaination of the hereditary influence on osteoporosis.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-10-0582","type":"journal-article","created":{"date-parts":[[2010,10,7]],"date-time":"2010-10-07T02:08:10Z","timestamp":1286417290000},"page":"123-131","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":43,"title":["Wnt receptors, bone mass, and fractures: gene-wide association analysis of LRP5 and LRP6 polymorphisms with 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