{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:33:34Z","timestamp":1792719214057,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2011,10,25]],"date-time":"2011-10-25T00:00:00Z","timestamp":1319500800000},"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":[[2012,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Dynamic bone histomorphometry is the standard method for measuring bone remodeling at the level of individual events. Although dynamic bone histomorphometry is an invaluable tool for understanding osteoporosis and other metabolic bone diseases, the technique's two-dimensional nature requires the use of stereology and prevents measures of individual remodeling event number and size. Here, we used a novel three-dimensional fluorescence imaging technique to achieve measures of individual resorption cavities and formation events. We performed this three-dimensional histomorphometry approach using a common model of postmenopausal osteoporosis, the ovariectomized rat. The three-dimensional images demonstrated the spatial relationship between resorption cavities and formation events consistent with the hemiosteonal model of cancellous bone remodeling. Established ovariectomy was associated with significant increases in the number of resorption cavities per unit bone surface (2.38\u2009\u00b1\u20090.24\u2009mm\u22122 sham surgery versus 3.86\u2009\u00b1\u20090.35\u2009mm\u22122 bilateral ovariectomy [OVX], mean\u2009\u00b1\u2009SD, p\u2009&amp;lt;\u20090.05) and total volume occupied by cavities per unit bone volume (0.38%\u2009\u00b1\u20090.06% sham versus 1.12%\u2009\u00b1\u20090.18% OVX, p\u2009&amp;lt;\u20090.001), but there was no difference in surface area per resorption cavity, maximum cavity depth, or cavity volume. In addition, we found that established ovariectomy is associated with increased size of bone formation events because of the merging of formation events (23,700\u2009\u00b1\u20096,890\u2009\u00b5m2 sham verusus 33,300\u2009\u00b1\u20097,950\u2009\u00b5m2 OVX). No differences in mineral apposition rate (determined in 3D) were associated with established ovariectomy. That established estrogen depletion is associated with increased number of remodeling events with only subtle changes in remodeling event size suggests that circulating estrogens may have their primary effect on the origination of new basic multicellular units with relatively little effect on the progression and termination of active remodeling events. \u00a9 2012 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.553","type":"journal-article","created":{"date-parts":[[2011,10,25]],"date-time":"2011-10-25T16:11:51Z","timestamp":1319559111000},"page":"486-495","source":"Crossref","is-referenced-by-count":51,"title":["Three-dimensional dynamic bone histomorphometry"],"prefix":"10.1093","volume":"27","author":[{"given":"Craig R","family":"Slyfield","sequence":"first","affiliation":[{"name":"Biomedical Mechanics Laboratories, Sibley School of Mechanical and Aerospace Engineering and Biomedical Engineering, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeniy V","family":"Tkachenko","sequence":"additional","affiliation":[{"name":"Biomedical Mechanics Laboratories, Sibley School of Mechanical and Aerospace Engineering and Biomedical Engineering, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Biomedical Mechanics Laboratories, Sibley School of Mechanical and Aerospace Engineering and Biomedical Engineering, Cornell University, Ithaca, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,10,25]]},"reference":[{"issue":"6","key":"2024020318224582200_bib1","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.2106\/00004623-196648060-00018","article-title":"Bone dynamics in metabolic bone disease","volume":"48","author":"Frost","year":"1966","journal-title":"J Bone Joint Surg."},{"issue":"2","key":"2024020318224582200_bib2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/jbmr.5650110203","article-title":"A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates","volume":"11","author":"Parfitt","year":"1996","journal-title":"J Bone Miner Res."},{"issue":"6","key":"2024020318224582200_bib3","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S8756-3282(02)00735-4","article-title":"Misconceptions (2): turnover is always higher in cancellous than in cortical bone","volume":"30","author":"Parfitt","year":"2002","journal-title":"Bone."},{"issue":"21","key":"2024020318224582200_bib4","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1056\/NEJMra053077","article-title":"Bone quality\u2014the material and structural basis of bone strength and fragility","volume":"354","author":"Seeman","year":"2006","journal-title":"N Engl J Med."},{"issue":"6","key":"2024020318224582200_bib5","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.bone.2008.02.001","article-title":"How can bone turnover modify bone strength independent of bone mass?","volume":"42","author":"Hernandez","year":"2008","journal-title":"Bone."},{"key":"2024020318224582200_bib6","author":"Kummari"},{"key":"2024020318224582200_bib7","first-page":"143","volume-title":"Bone histomorphometry: techniques and interpretation","author":"Parfitt","year":"1983"},{"key":"2024020318224582200_bib8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/978-0-585-38227-2_7","volume-title":"Methods in bone biology","author":"Compston","year":"1997","edition":"1st ed"},{"issue":"6","key":"2024020318224582200_bib9","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/jbmr.5650020617","article-title":"Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee","volume":"2","author":"Parfitt","year":"1987","journal-title":"J Bone Miner Res."},{"issue":"1","key":"2024020318224582200_bib10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0169-6009(08)80165-1","article-title":"Stereological considerations concerning the measurement of individual osteoid seams and resorption cavities","volume":"26","author":"Hauge","year":"1994","journal-title":"J Bone Miner Res."},{"key":"2024020318224582200_bib11","volume-title":"Unbiased stereology: three dimensional measurement in microscopy","author":"Howard","year":"1998"},{"key":"2024020318224582200_bib12","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1365-2818.1990.tb03038.x","article-title":"A direct method for fast three-dimensional serial reconstruction","volume":"159","author":"Odgaard","year":"1990","journal-title":"J Microsc."},{"issue":"3","key":"2024020318224582200_bib13","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S8756-3282(97)00122-1","article-title":"Three-dimensional imaging of trabecular bone using the computer numerically controlled milling technique","volume":"21","author":"Beck","year":"1997","journal-title":"Bone."},{"issue":"Pt 2","key":"2024020318224582200_bib14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1365-2818.2007.01721.x","article-title":"Automated high-resolution three-dimensional fluorescence imaging of large biological specimens","volume":"225","author":"Kazakia","year":"2007","journal-title":"J Microsc."},{"issue":"1","key":"2024020318224582200_bib15","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1365-2818.2009.03204.x","article-title":"Three-dimensional surface texture visualization of bone tissue through epifluorescence-based serial block face imaging","volume":"236","author":"Slyfield","year":"2009","journal-title":"J Microsc."},{"issue":"3","key":"2024020318224582200_bib16","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.bone.2009.05.019","article-title":"Voxel size and measures of individual resorption cavities in three-dimensional images of cancellous bone","volume":"45","author":"Tkachenko","year":"2009","journal-title":"Bone."},{"issue":"1","key":"2024020318224582200_bib17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s00223-001-1086-y","article-title":"Estrogen and \u201cexercise\u201d have a synergistic effect in preventing bone loss in the lumbar vertebra and femoral neck of the ovariectomized rat","volume":"72","author":"Li","year":"2003","journal-title":"Calcif Tissue Int."},{"issue":"3","key":"2024020318224582200_bib18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/8756-3282(93)90185-D","article-title":"Maintaining restored bone with bisphosphonate in the ovariectomized rat skeleton: dynamic histomorphometry of changes in bone mass","volume":"14","author":"Jee","year":"1993","journal-title":"Bone."},{"issue":"2","key":"2024020318224582200_bib19","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1359\/JBMR.041114","article-title":"Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling","volume":"20","author":"Riggs","year":"2005","journal-title":"J Bone Miner Res."},{"key":"2024020318224582200_bib20","volume-title":"Osteoporosis","author":"Parfitt","year":"2008","edition":"3rd ed."},{"issue":"6","key":"2024020318224582200_bib21","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/BF02556007","article-title":"Long-term effects of ovariectomy and aging on the rat skeleton","volume":"45","author":"Wronski","year":"1989","journal-title":"Calcif Tiss Int."},{"issue":"1B","key":"2024020318224582200_bib22","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/0002-9343(87)90274-9","article-title":"Trabecular bone architecture in the pathogenesis and prevention of fracture","volume":"82","author":"Parfitt","year":"1987","journal-title":"Am J Med."},{"issue":"4","key":"2024020318224582200_bib23","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1359\/jbmr.2001.16.4.688","article-title":"A three-dimensional simulation of age-related remodeling in trabecular bone","volume":"16","author":"van der Linden","year":"2001","journal-title":"J Bone Miner Res."},{"issue":"8","key":"2024020318224582200_bib24","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1007\/s10439-009-9726-x","article-title":"Removal of out-of-plane fluorescence for single cell visualization and quantification in cryo-imaging","volume":"37","author":"Steyer","year":"2009","journal-title":"Ann Biomed Eng."},{"issue":"1","key":"2024020318224582200_bib25","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/BF02546434","article-title":"Number, size and arrangement of osteoblasts in osteons at different stages of formation","volume":"21","author":"Marotti","year":"1975","journal-title":"Calcif Tiss Int."},{"issue":"5","key":"2024020318224582200_bib26","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1210\/endo.134.5.8156931","article-title":"The effects of raloxifene on tibia histomorphometry in ovariectomized rats","volume":"134","author":"Evans","year":"1994","journal-title":"Endocrinology."},{"key":"2024020318224582200_bib27","volume-title":"Bone histomorphometry: techniques and interpretation","author":"Recker","year":"1983"},{"issue":"7","key":"2024020318224582200_bib28","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1002\/jbmr.141","article-title":"Guidelines for assessment of bone microstructure in rodents using micro-computed tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"J Bone Miner Res."},{"issue":"5","key":"2024020318224582200_bib29","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0221-8747(84)90065-1","article-title":"Reconstruction of the resorptive site in iliac trabecular bone: a kinetic model for bone resorption in 20 normal individuals","volume":"5","author":"Eriksen","year":"1984","journal-title":"Metab Bone Dis Relat Res."},{"issue":"5","key":"2024020318224582200_bib30","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S8756-3282(01)00424-0","article-title":"How many patients are needed? Variation and design considerations in bone histomorphometry","volume":"28","author":"Hauge","year":"2001","journal-title":"Bone."},{"issue":"4","key":"2024020318224582200_bib31","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S0736-0266(01)00185-1","article-title":"Quantitative computed tomography estimates of the mechanical properties of human vertebral trabecular bone","volume":"20","author":"Kopperdahl","year":"2002","journal-title":"J Orth Res."},{"issue":"8","key":"2024020318224582200_bib32","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1002\/jbmr.5650090820","article-title":"Benefit of systemically administered rhIGF I and rhIGF I\/IGFBP 3 on cancellous bone in ovariectomized rats","volume":"9","author":"Bagi","year":"1994","journal-title":"J Bone Miner Res."},{"issue":"8","key":"2024020318224582200_bib33","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1210\/endo.136.8.7628403","article-title":"Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells","volume":"136","author":"Dobnig","year":"1995","journal-title":"Endocrinology."},{"issue":"11","key":"2024020318224582200_bib34","doi-asserted-by":"crossref","first-page":"5127","DOI":"10.1210\/endo.136.11.7588250","article-title":"Intermittent parathyroid hormone treatment increases osteoblast number, steady state messenger ribonucleic acid levels for osteocalcin, and bone formation in tibial metaphysis of hypophysectomized female rats","volume":"136","author":"Schmidt","year":"1995","journal-title":"Endocrinology."},{"issue":"4","key":"2024020318224582200_bib35","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/jbmr.5650110402","article-title":"Temporal expression of the anabolic action of PTH in cancellous bone of ovariectomized rats","volume":"11","author":"Meng","year":"1996","journal-title":"J Bone Miner Res."},{"key":"2024020318224582200_bib36","first-page":"133","volume-title":"Bone histomorphometry: techniques and interpretation","author":"Frost","year":"1983"},{"issue":"4","key":"2024020318224582200_bib37","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/ar.10014","article-title":"Super-osteons (remodeling clusters) in the cortex of the femoral shaft: influence of age and gender","volume":"264","author":"Bell","year":"2001","journal-title":"Anat Rec."},{"issue":"3","key":"2024020318224582200_bib38","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/jcb.240550303","article-title":"Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone","volume":"55","author":"Parfitt","year":"1994","journal-title":"J Cell Biochem."},{"issue":"5066","key":"2024020318224582200_bib39","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1126\/science.1621100","article-title":"Increased osteoclast development after estrogen loss: mediation by interleukin-6","volume":"257","author":"Jilka","year":"1992","journal-title":"Science."},{"issue":"6","key":"2024020318224582200_bib40","first-page":"500","article-title":"Estrogen loss upregulates hematopoiesis in the mouse: a mediating role of IL-6","volume":"23","author":"Jilka","year":"1995","journal-title":"Exp Hemat."},{"issue":"46","key":"2024020318224582200_bib41","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."},{"issue":"10","key":"2024020318224582200_bib42","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1038\/nm1096-1132","article-title":"Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-[beta]","volume":"2","author":"Hughes","year":"1996","journal-title":"Nat Med."},{"issue":"6","key":"2024020318224582200_bib43","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1084\/jem.183.6.2581","article-title":"The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures","volume":"183","author":"Romas","year":"1996","journal-title":"J Exp Med."},{"issue":"5","key":"2024020318224582200_bib44","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."},{"issue":"2","key":"2024020318224582200_bib45","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/jbmr.5650110203","article-title":"Theoretical perspective: a new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates","volume":"11","author":"Parfitt","year":"1996","journal-title":"J Bone Miner Res."}],"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.553","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/27\/2\/486\/56561909\/553_ftp.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/27\/2\/486\/56561909\/553_ftp.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:48:25Z","timestamp":1710341305000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/27\/2\/486-495\/7598475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,25]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2011,10,25]]},"published-print":{"date-parts":[[2012,2,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.553","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,2,1]]},"published":{"date-parts":[[2011,10,25]]}}}