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While this was a plausible model then, new data over the intervening years suggest a need to modify these concepts. Indeed, based largely on rodent studies, a \u201crevisionist\u201d view of the pathogenesis of osteoporosis has been proposed recently that attempts a paradigm shift from the estrogen-centric model to one in which bone loss is largely independent of estrogen deficiency and is driven instead by cell-autonomous age-related factors. However, detailed clinical investigative studies using quantitative computed tomography demonstrate that the onset of cortical bone loss in humans is closely tied to estrogen deficiency; thus the estrogen-centric view is likely correct for cortical bone, which comprises over 80% of the skeleton and is the major structural determinant of fracture risk at most skeletal sites. By contrast, these same studies also demonstrate that trabecular bone loss begins in sex hormone\u2013replete young adults of both sexes. This suggests that a significant proportion of trabecular bone loss is either estrogen-independent or, as suggested by some studies, requires higher levels for its regulation. In this perspective, we critically review these and other findings, leading us to conclude that our original model requires modification but not revision. \u00a9 2011 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.262","type":"journal-article","created":{"date-parts":[[2010,10,6]],"date-time":"2010-10-06T20:46:52Z","timestamp":1286398012000},"page":"441-451","source":"Crossref","is-referenced-by-count":304,"title":["The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: Is a revision needed?"],"prefix":"10.1093","volume":"26","author":[{"given":"Sundeep","family":"Khosla","sequence":"first","affiliation":[{"name":"Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"L Joseph","family":"Melton","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B Lawrence","family":"Riggs","sequence":"additional","affiliation":[{"name":"Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,10,6]]},"reference":[{"key":"2024020318064610200_bib1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/0002-9343(83)90860-4","article-title":"Evidence for two distinct syndromes of involutional osteoporosis","volume":"75","author":"Riggs","year":"1983","journal-title":"Am J Med."},{"key":"2024020318064610200_bib2","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1359\/jbmr.1998.13.5.763","article-title":"A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging 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