{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:05:45Z","timestamp":1789380345209,"version":"build-2803163510"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[1996,3,1]],"date-time":"1996-03-01T00:00:00Z","timestamp":825638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Comprehensive Research on Aging and Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1996,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>PvuII and XbaI restriction fragment length polymorphisms (RFLPs) of the estrogen receptor (ER) gene and its relation to bone mineral density (BMD) were examined in 238 postmenopausal healthy women aged 45\u201391 years (66.3 \u00b1 0.6 years, mean \u00b1 standard error of the mean [SEM]) in Japan. The RFLPs were represented as Pp (PvuII) and Xx (XbaI), with capital letters signifying the absence of and small letters the presence of restriction sites. In the PPxx genotype (n = 18), Z score values of BMD were significantly lower than those for other genotypes (n = 220) (lumbar spine, \u22120.746 vs. \u22120.065 [p = 0.022]; total body, \u22120.482 vs. 0.308 [p = 0.002]). We classified the subjects into three genotypes with allelic haplotype: homozygote of the Px haplotype was expressed as the 11 genotype, heterozygote of the Px haplotype as the 10 genotype, and the one lacking the Px haplotype as the 00 genotype. The PpXx genotype was not included in this analysis because the allelic haplotypes are uncertain. The Px haplotype was associated with a low BMD in postmenopausal women (Z score for the lumbar spine, \u22120.746 vs. \u22120.279 vs. 0.083, for the 11, 10, 00 genotypes, respectively [p = 0.029]; Z score for the total body, \u22120.482 vs. 0.164 vs. 0.427, respectively [p = 0.003]). We suggest that some variation of the ER gene linked to these RFLPs is associated with low BMD and that this at least partly explains the cause of postmenopausal osteoporosis in Japanese women.<\/jats:p>","DOI":"10.1002\/jbmr.5650110304","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T15:31:40Z","timestamp":1265211100000},"page":"306-311","source":"Crossref","is-referenced-by-count":385,"title":["Association of bone mineral density with polymorphism of the estrogen receptor gene"],"prefix":"10.1093","volume":"11","author":[{"given":"Shinji","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Faculty of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Faculty of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Dr. Hosoi","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Faculty of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyoshi","family":"Ouchi","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Faculty of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Shiraki","sequence":"additional","affiliation":[{"name":"Research Institute and Practice for Involutional Diseases, Nagano, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Orimo","sequence":"additional","affiliation":[{"name":"Ministry of Finance, Tokyo Hospital, Tokyo, Japan"},{"name":"Department of Geriatrics, Faculty of Medicine, University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1996,3,1]]},"reference":[{"key":"2024013114254246700_bib1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/jbmr.5650060606","article-title":"Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates","volume":"6","author":"Slemenda","year":"1991","journal-title":"J Bone Miner Res"},{"key":"2024013114254246700_bib2","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":"2024013114254246700_bib3","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/367284a0","article-title":"Prediction of bone density from vitamin D receptor alleles","volume":"367","author":"Morrison","year":"1994","journal-title":"Nature"},{"key":"2024013114254246700_bib4","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0140-6736(94)91690-X","article-title":"Vitamin D receptor gene polymorphism and bone mineral density in healthy Japanese women","volume":"344","author":"Yamagata","year":"1994","journal-title":"Lancet"},{"key":"2024013114254246700_bib5","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1172\/JCI117568","article-title":"Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus","volume":"94","author":"Hustmyer","year":"1994","journal-title":"J Clin Invest"},{"key":"2024013114254246700_bib6","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S0140-6736(94)92297-7","article-title":"Vitamin D receptor genotypes in osteoporosis","volume":"344","author":"Melhus","year":"1994","journal-title":"Lancet"},{"key":"2024013114254246700_bib7","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1136\/bmj.310.6991.1357","article-title":"Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: a twin study in Britain","volume":"310","author":"Spector","year":"1995","journal-title":"Brit Med J"},{"key":"2024013114254246700_bib8","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1002\/jbmr.5650100620","article-title":"Vitamin D receptor alleles and rates of bone loss: Influences of years since menopause and calcium intake","volume":"10","author":"Krall","year":"1995","journal-title":"J Bone Miner Res"},{"key":"2024013114254246700_bib9","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1002\/jbmr.5650100621","article-title":"The Bsml vitamin D receptor restriction fragment length polymorphism (BB) predicts low bone density in premenopausal black and white women","volume":"10","author":"Fleet","year":"1995","journal-title":"J Bone Miner Res"},{"key":"2024013114254246700_bib10","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1056\/NEJM198606263142605","article-title":"Involutional osteoporosis","volume":"314","author":"Riggs","year":"1986","journal-title":"New Engl J Med"},{"key":"2024013114254246700_bib11","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/S0140-6736(76)92217-0","article-title":"Long-term prevention of postmenopausal osteoporosis by oestrogen: evidence for an increased bone mass after delayed onset of oestrogen treatment","volume":"1","author":"Lindsay","year":"1976","journal-title":"Lancet"},{"key":"2024013114254246700_bib12","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0025-6196(12)65642-0","article-title":"Estrogen replacement therapy: current recommendations","volume":"63","author":"Lufkin","year":"1988","journal-title":"Mayo Clin Proc"},{"key":"2024013114254246700_bib13","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1126\/science.3164526","article-title":"Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells","volume":"241","author":"Komm","year":"1988","journal-title":"Science"},{"key":"2024013114254246700_bib14","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.3388021","article-title":"Evidence of estrogen receptors in normal human osteoblast-like cells","volume":"241","author":"Eriksen","year":"1988","journal-title":"Science"},{"key":"2024013114254246700_bib15","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1210\/endo.135.2.8033827","article-title":"Cell cycle-dependent expression of estrogen receptor and effect of estrogen on proliferation of synchronized human osteoblast-like osteosarcoma cells","volume":"135","author":"Ikegami","year":"1994","journal-title":"Endocrinology"},{"key":"2024013114254246700_bib16","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/jbmr.5650050802","article-title":"Osteoclasts isolated from membranous bone in children exhibited nuclear estrogen and progesterone receptors","volume":"5","author":"Pensler","year":"1990","journal-title":"J Bone Miner Res"},{"key":"2024013114254246700_bib17","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1056\/NEJM199410203311604","article-title":"Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man","volume":"331","author":"Smith","year":"1994","journal-title":"New Engl J Med"},{"key":"2024013114254246700_bib18","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1126\/science.7985022","article-title":"Insights from the study of animals lacking functional estrogen receptor","volume":"266","author":"Korach","year":"1994","journal-title":"Science"},{"key":"2024013114254246700_bib19","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1093\/nar\/15.2.866","article-title":"PvuII RFLP inside the human estrogen receptor gene","volume":"15","author":"Castagnoli","year":"1987","journal-title":"Nucleic Acids Res"},{"key":"2024013114254246700_bib20","doi-asserted-by":"crossref","first-page":"7208","DOI":"10.1093\/nar\/16.14.7208","article-title":"Human estrogen receptor (ESR) gene locus: PssI dimorphism","volume":"16","author":"Coleman","year":"1988","journal-title":"Nucleic Acids Res"},{"key":"2024013114254246700_bib21","doi-asserted-by":"crossref","first-page":"8364","DOI":"10.1093\/nar\/17.20.8364","article-title":"Identification of a variant from of the human estrogen receptor with an amino acid replacement","volume":"17","author":"Garcia","year":"1989","journal-title":"Nucleic Acids Res"},{"key":"2024013114254246700_bib22","first-page":"1116","article-title":"Polymorphisms at the estrogen receptor (ESR) locus and linkage relationships on chromosome 6q","volume":"51","author":"Zuppan","year":"1989","journal-title":"Cytogenet Cell Genet"},{"key":"2024013114254246700_bib23","first-page":"145","article-title":"Estrogen receptor expression in human breast cancer associated with an estrogen receptor gene restriction fragment length polymorphism","volume":"49","author":"Hill","year":"1989","journal-title":"Cancer Res"},{"key":"2024013114254246700_bib24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/BF01805976","article-title":"Genomic DNA analysis of the estrogen receptor gene in breast cancer","volume":"14","author":"Parl","year":"1989","journal-title":"Breast Cancer Res Treat"},{"key":"2024013114254246700_bib25","first-page":"77","article-title":"Analysis of the PvuII restriction fragment-length polymorphism and exon structure of the estrogen receptor gene in breast cancer and peripheral blood","volume":"52","author":"Yaich","year":"1992","journal-title":"Cancer Res"},{"key":"2024013114254246700_bib26","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/0140-6736(90)90410-7","article-title":"Oestrogen receptor B-region polymorphism and spontaneous abortion in women with breast cancer","volume":"335","author":"Lehrer","year":"1990","journal-title":"Lancet"},{"key":"2024013114254246700_bib27","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1093\/oxfordjournals.aje.a116645","article-title":"Risk of miscarriage and a common variant of the estrogen receptor gene","volume":"137","author":"Taylor","year":"1993","journal-title":"Am J Epidemiol"},{"key":"2024013114254246700_bib28","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1161\/01.HYP.21.4.439","article-title":"Estrogen receptor variant and hypertension in women","volume":"21","author":"Lehrer","year":"1993","journal-title":"Hypertension"},{"issue":"Suppl","key":"2024013114254246700_bib29","first-page":"118","article-title":"Cross calibrated standard values of vertebral bone mineral density in Japanese","volume":"9","author":"Shiraki","year":"1991","journal-title":"J Bone Miner Metabol"},{"key":"2024013114254246700_bib30","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1093\/clinchem\/38.11.2233","article-title":"Sandwich immunoassay for intact human osteocalcin","volume":"38","author":"Hosoda","year":"1992","journal-title":"Clin Chem"},{"key":"2024013114254246700_bib31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0169-6009(91)90143-N","article-title":"Urinary excretion of pyridinium crosslinks: a new marker of bone resorption in metabolic bone disease","volume":"8","author":"Uebelhart","year":"1990","journal-title":"Bone Miner"},{"key":"2024013114254246700_bib32","doi-asserted-by":"crossref","first-page":"11162","DOI":"10.1073\/pnas.90.23.11162","article-title":"Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene","volume":"90","author":"Lubahn","year":"1993","journal-title":"Proc Natl Acad Sci"}],"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.5650110304","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/11\/3\/306\/56503359\/5650110304.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/11\/3\/306\/56503359\/5650110304.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:01:55Z","timestamp":1710342115000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/11\/3\/306-311\/7501174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,3,1]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[1996,3,1]]},"published-print":{"date-parts":[[1996,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.5650110304","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1996,3,1]]},"published":{"date-parts":[[1996,3,1]]}}}