{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T12:48:17Z","timestamp":1792241297508,"version":"4.4.0"},"reference-count":56,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Trends in Endocrinology & Metabolism"],"published-print":{"date-parts":[[2012,11]]},"DOI":"10.1016\/j.tem.2012.03.008","type":"journal-article","created":{"date-parts":[[2012,5,16]],"date-time":"2012-05-16T06:11:36Z","timestamp":1337148696000},"page":"576-581","source":"Crossref","is-referenced-by-count":858,"title":["Estrogen and the skeleton"],"prefix":"10.1016","volume":"23","author":[{"given":"Sundeep","family":"Khosla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merry Jo","family":"Oursler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Monroe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tem.2012.03.008_bib0005","first-page":"298","article-title":"Post-menopausal osteoporosis","volume":"55","author":"Albright","year":"1940","journal-title":"Trans. Assoc. Am. Physicians"},{"key":"10.1016\/j.tem.2012.03.008_bib0010","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/jbmr.262","article-title":"The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: is a revision needed?","volume":"26","author":"Khosla","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0015","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","volume":"i","author":"Lindsay","year":"1976","journal-title":"Lancet"},{"key":"10.1016\/j.tem.2012.03.008_bib0020","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1210\/er.2008-0002","article-title":"Osteoporosis in men","volume":"29","author":"Khosla","year":"2008","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.tem.2012.03.008_bib0025","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1172\/JCI10942","article-title":"Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men","volume":"106","author":"Falahati-Nini","year":"2000","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.tem.2012.03.008_bib0030","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1359\/jbmr.1998.13.7.1124","article-title":"Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability","volume":"13","author":"Hannon","year":"1998","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7326\/0003-4819-117-1-1","article-title":"Treatment of postmenopausal osteoporosis with transdermal estrogen","volume":"117","author":"Lufkin","year":"1992","journal-title":"Ann. Intern. Med."},{"key":"10.1016\/j.tem.2012.03.008_bib0040","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/jbmr.5650110307","article-title":"Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis","volume":"11","author":"Garnero","year":"1996","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0045","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1359\/jbmr.2001.16.9.1575","article-title":"Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers","volume":"16","author":"Hauge","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0050","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2353\/ajpath.2009.080627","article-title":"A physical mechanism for coupling bone resorption and formation in adult human bone","volume":"174","author":"Andersen","year":"2009","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.tem.2012.03.008_bib0055","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jbmr.320","article-title":"The amazing osteocyte","volume":"26","author":"Bonewald","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0060","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/nm.2448","article-title":"Matrix-embedded cells control osteoclast formation","volume":"17","author":"Xiong","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.tem.2012.03.008_bib0065","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/nm.2452","article-title":"Evidence for osteocyte regulation of bone homeostasis through RANKL expression","volume":"17","author":"Nakashima","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.tem.2012.03.008_bib0070","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1210\/er.2007-0014","article-title":"Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease","volume":"29","author":"Kearns","year":"2008","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.tem.2012.03.008_bib0075","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nm.1979","article-title":"TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation","volume":"15","author":"Tang","year":"2009","journal-title":"Nat. Med."},{"key":"10.1016\/j.tem.2012.03.008_bib0080","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.bone.2010.11.020","article-title":"Denosumab and bisphosphonates: different mechanisms of action and effects","volume":"48","author":"Baron","year":"2011","journal-title":"Bone"},{"key":"10.1016\/j.tem.2012.03.008_bib0085","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cmet.2006.05.012","article-title":"Bidirectional ephrinB2\u2013EphB4 signaling controls bone homeostasis","volume":"4","author":"Zhao","year":"2006","journal-title":"Cell Metab."},{"key":"10.1016\/j.tem.2012.03.008_bib0090","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1038\/nm.2489","article-title":"Suppression of bone formation by osteoclastic expression of semaphorin 4D","volume":"17","author":"Negishi-Koga","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.tem.2012.03.008_bib0095","doi-asserted-by":"crossref","first-page":"20764","DOI":"10.1073\/pnas.0805133106","article-title":"Regulation of bone formation by osteoclasts involves Wnt\/BMP signaling and the chemokine sphingosine-1-phosphate","volume":"105","author":"Pederson","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.tem.2012.03.008_bib0100","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1056\/NEJMct1004903","article-title":"Bisphosphonates for osteoporosis","volume":"363","author":"Favus","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.tem.2012.03.008_bib0105","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1056\/NEJMoa0809493","article-title":"Denosumab for prevention of fractures in postmenopausal women with osteoporosis","volume":"361","author":"Cummings","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.tem.2012.03.008_bib0110","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1210\/jc.82.9.3128","article-title":"The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone","volume":"82","author":"Tomkinson","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"10.1016\/j.tem.2012.03.008_bib0115","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1359\/jbmr.1998.13.8.1243","article-title":"The role of estrogen in the control of rat osteocyte apoptosis","volume":"13","author":"Tomkinson","year":"1998","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0120","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.bone.2009.11.006","article-title":"Osteocyte apoptosis and control of bone resorption following ovariectomy in mice","volume":"46","author":"Emerton","year":"2010","journal-title":"Bone"},{"key":"10.1016\/j.tem.2012.03.008_bib0125","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1074\/jbc.M111.294959","article-title":"Pro-survival effects of 17beta-estradiol on osteocytes are mediated by NO\/cGMP via differential actions of PKG I and II","volume":"287","author":"Marathe","year":"2011","journal-title":"J. Biol. Chem."},{"issue":"Suppl. 1","key":"10.1016\/j.tem.2012.03.008_bib0130","article-title":"Estrogen receptor alpha expression in osteocytes is necessary to maintain normal bone mineral density and reduce bone loss due to unloading","volume":"26","author":"Imai","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0135","doi-asserted-by":"crossref","first-page":"6613","DOI":"10.1073\/pnas.88.15.6613","article-title":"Avian osteoclasts as estrogen target cells","volume":"88","author":"Oursler","year":"1991","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.tem.2012.03.008_bib0140","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cell.2007.07.025","article-title":"Estrogen prevents bone loss via estrogen receptor alpha and induction of fas ligand in osteoclasts","volume":"130","author":"Nakamura","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.tem.2012.03.008_bib0145","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1210\/me.2009-0354","article-title":"The estrogen receptor-alpha in osteoclasts mediates the protective effects of estrogens on cancellous but not cortical bone","volume":"24","author":"Martin-Millan","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.tem.2012.03.008_bib0150","doi-asserted-by":"crossref","first-page":"7829","DOI":"10.1073\/pnas.130200197","article-title":"Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression","volume":"97","author":"Shevde","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.tem.2012.03.008_bib0155","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1210\/en.142.9.3800","article-title":"Androgens suppress osteoclast formation induced by RANKL and macrophage-colony stimulating factor","volume":"142","author":"Huber","year":"2001","journal-title":"Endocrinology"},{"key":"10.1016\/j.tem.2012.03.008_bib0160","doi-asserted-by":"crossref","first-page":"8836","DOI":"10.1074\/jbc.M010764200","article-title":"Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kB ligand (RANKL)-induced JNK activation","volume":"276","author":"Srivastava","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.tem.2012.03.008_bib0165","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.yexcr.2009.01.014","article-title":"Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor alpha with BCAR1 and Traf6","volume":"315","author":"Robinson","year":"2009","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0170","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1172\/JCI200317215","article-title":"Role of RANK ligand in mediating increased bone resorption in early postmenopausal women","volume":"111","author":"Eghbali-Fatourechi","year":"2003","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.tem.2012.03.008_bib0175","doi-asserted-by":"crossref","first-page":"4367","DOI":"10.1210\/en.140.9.4367","article-title":"Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells","volume":"140","author":"Hofbauer","year":"1999","journal-title":"Endocrinology"},{"issue":"Suppl. 1","key":"10.1016\/j.tem.2012.03.008_bib0180","first-page":"S146","article-title":"Estrogen and testosterone have opposite effects on circulating OPG levels following induction of hypogonadism and aromatase inhibition in normal elderly men: potential mechanism for differential effects of estrogen versus testosterone on bone resorption","volume":"16","author":"Khosla","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0185","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1056\/NEJM199502023320506","article-title":"Bone marrow, cytokines, and bone remodeling: Emerging insights into the pathophysiology of osteoporosis","volume":"332","author":"Manolagas","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.tem.2012.03.008_bib0190","doi-asserted-by":"crossref","first-page":"5134","DOI":"10.1073\/pnas.88.12.5134","article-title":"Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells","volume":"88","author":"Pacifici","year":"1991","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.tem.2012.03.008_bib0195","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1172\/JCI116179","article-title":"Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors","volume":"91","author":"Tanaka","year":"1993","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.tem.2012.03.008_bib0200","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1172\/JCI117187","article-title":"Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats","volume":"93","author":"Kimble","year":"1994","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.tem.2012.03.008_bib0205","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1172\/JCI119333","article-title":"Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency","volume":"99","author":"Ammann","year":"1997","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.tem.2012.03.008_bib0210","doi-asserted-by":"crossref","first-page":"28890","DOI":"10.1074\/jbc.271.46.28890","article-title":"Estrogen deficiency increases the ability of stromal cells to support murine osteoclastogenesis via an interleukin-1-and tumor necrosis factor-mediated stimulation of macrophage colony-stimulating factor production","volume":"271","author":"Kimble","year":"1996","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.tem.2012.03.008_bib0215","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1172\/JCI117606","article-title":"Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice","volume":"94","author":"Kitazawa","year":"1994","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.tem.2012.03.008_bib0220","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1359\/jbmr.070207","article-title":"Effect of blockade of TNF-\u03b1 and interleukin-1 action on bone resorption in early postmenopausal women","volume":"22","author":"Charatcharoenwitthaya","year":"2007","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0225","doi-asserted-by":"crossref","first-page":"13960","DOI":"10.1073\/pnas.251534698","article-title":"Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo","volume":"98","author":"Roggia","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.tem.2012.03.008_bib0230","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1172\/JCI11066","article-title":"Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-a","volume":"106","author":"Cenci","year":"2000","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.tem.2012.03.008_bib0235","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1359\/jbmr.1997.12.3.479","article-title":"The role of the T-lymphocyte in estrogen deficiency osteopenia","volume":"12","author":"Sass","year":"1997","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0240","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1359\/jbmr.060726","article-title":"T lymphocyte-deficient mice lose trabecular bone mass with ovariectomy","volume":"21","author":"Lee","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0245","first-page":"719","article-title":"Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity","volume":"104","author":"Kousteni","year":"2001","journal-title":"Cell"},{"key":"10.1016\/j.tem.2012.03.008_bib0250","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1172\/JCI200317261","article-title":"Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids","volume":"111","author":"Kousteni","year":"2003","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.tem.2012.03.008_bib0255","doi-asserted-by":"crossref","first-page":"27285","DOI":"10.1074\/jbc.M702810200","article-title":"Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids","volume":"282","author":"Almeida","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.tem.2012.03.008_bib0260","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1210\/me.2007-0259","article-title":"Gone with the Wnts: beta-catenin, T-cell factor, forkhead box O, and oxidative stress in age-dependent diseases of bone, lipid, and glucose metabolism","volume":"21","author":"Manolagas","year":"2007","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.tem.2012.03.008_bib0265","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nm.1954","article-title":"Inhibition of osteoblastic bone formation by nuclear factor-kappaB","volume":"15","author":"Chang","year":"2009","journal-title":"Nat. Med."},{"key":"10.1016\/j.tem.2012.03.008_bib0270","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/jbmr.128","article-title":"Regulation of circulating sclerostin levels by sex steroids in women and men","volume":"26","author":"Modder","year":"2011","journal-title":"J. Bone Miner. Res."},{"issue":"Suppl. 1","key":"10.1016\/j.tem.2012.03.008_bib0275","article-title":"ERalpha-deletion from osteoblast progenitors abolishes the protective effect of estrogens on cortical bone mass in both female and male mice","volume":"26","author":"Iyer","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.tem.2012.03.008_bib0280","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1677\/JOE-10-0209","article-title":"Skeletal sexual dimorphism: relative contribution of sex steroids, GH\u2013IGF1, and mechanical loading","volume":"207","author":"Callewaert","year":"2010","journal-title":"J. Endocrinol."}],"container-title":["Trends in Endocrinology & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043276012000525?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043276012000525?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,11,23]],"date-time":"2018-11-23T07:21:26Z","timestamp":1542957686000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043276012000525"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11]]},"references-count":56,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["S1043276012000525"],"URL":"https:\/\/doi.org\/10.1016\/j.tem.2012.03.008","relation":{},"ISSN":["1043-2760"],"issn-type":[{"value":"1043-2760","type":"print"}],"subject":[],"published":{"date-parts":[[2012,11]]}}}