{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T08:05:30Z","timestamp":1789891530563,"version":"4.0.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"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":[[2004,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The genetic influence on bone loss in response to mechanical unloading was investigated within diaphyseal and distal femoral regions in three genetically distinct strains of mice. One mouse strain failed to lose bone after removal of function, whereas osteopenia was evident in multiple regions of the remaining two strains but in different areas of the bone.<\/jats:p>\n               <jats:p>Introduction: It is well recognized that susceptibility to osteoporosis is, in large measure, determined by the genome, but whether this influence is systemic or site-specific is not yet known. Here, the extent to which genetic variations influence regional bone loss caused by disuse was studied in the femora of adult female mice from three inbred strains.<\/jats:p>\n               <jats:p>Materials and Methods: Adult C57BL\/6J (B6), C3H\/HeJ (C3H), and BALB\/cByJ (BALB) mice were subjected to 15\u201321 days of disuse, achieved by hindlimb suspension, and six distinct anatomical regions of the femur were analyzed by high-resolution \u03bcCT.<\/jats:p>\n               <jats:p>Results and Conclusions: In B6 mice, the amount of disuse stimulated bone loss was relatively uniform across all regions, with 20% loss of trabecular bone and 10% loss of cortical bone. The degree of bone loss in BALB mice varied greatly, ranging from 59% in the metaphysis to 3% in the proximal diaphysis. In this strain, the nonuniformity of bone loss was directly related to the nonuniform distribution of baseline bone morphology (r2 = 0.94). In direct contrast with BALB and B6, disuse failed to produce significant losses of bone in any of the analyzed regions of the C3H mice. Instead, these animals displayed a unique compensatory mechanism to disuse, where the large loss of calcified tissue from the endocortical surface (\u221224%) was compensated for by an expansion of the periosteal envelope (10%). These data indicate a strong, yet complex, genetic dependence of the site-specific regulation of bone remodeling in response to a powerful catabolic signal. Consequently, the skeletal region of interest and the genetic make-up of the individual may have to be considered interdependently when considering the pathogenesis of osteoporosis or the efficacy of an intervention to prevent or recover bone loss.<\/jats:p>","DOI":"10.1359\/jbmr.040110","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T06:10:44Z","timestamp":1146118244000},"page":"607-613","source":"Crossref","is-referenced-by-count":106,"title":["Genetically Linked Site-Specificity of Disuse Osteoporosis"],"prefix":"10.1093","volume":"19","author":[{"given":"Stefan","family":"Judex","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Garman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Squire","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavin","family":"Busa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah-Rae","family":"Donahue","sequence":"additional","affiliation":[{"name":"Bone Biology Research Group, The Jackson Laboratory, Bar Harbor, Maine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clinton","family":"Rubin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019210276100_bib1","first-page":"199","article-title":"Bone mineral density changes in the forearm after immobilization","volume":"317","author":"Houde","year":"1995","journal-title":"Clin Orthop"},{"key":"2024013019210276100_bib2","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/S0140-6736(00)02217-0","article-title":"Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts","volume":"355","author":"Vico","year":"2000","journal-title":"Lancet"},{"key":"2024013019210276100_bib3","first-page":"17","author":"Shackelford","year":"1999"},{"key":"2024013019210276100_bib4","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1210\/edrv.20.6.0384","article-title":"Genetics of osteoporosis","volume":"20","author":"Eisman","year":"1999","journal-title":"Endocr Rev"},{"key":"2024013019210276100_bib5","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1210\/jcem-72-4-808","article-title":"Genetic factors in bone turnover","volume":"72","author":"Kelly","year":"1991","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019210276100_bib6","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1096\/fj.01-0913fje","article-title":"Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton","volume":"16","author":"Judex","year":"2002","journal-title":"FASEB J"},{"key":"2024013019210276100_bib7","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s002239900554","article-title":"Bone response to in vivo mechanical loading in two breeds of mice","volume":"63","author":"Akhter","year":"1998","journal-title":"Calcif Tissue Int"},{"key":"2024013019210276100_bib8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1385\/JCD:5:2:207","article-title":"Bone adaptation response to sham and bending stimuli in mice","volume":"5","author":"Akhter","year":"2002","journal-title":"J Clin Densitom"},{"key":"2024013019210276100_bib9","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s002230010060","article-title":"Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL\/6J mice but not in C3H\/Hej mice","volume":"66","author":"Kodama","year":"2000","journal-title":"Calcif Tissue Int"},{"key":"2024013019210276100_bib10","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S8756-3282(99)00155-6","article-title":"Cortical tibial bone volume in two strains of mice: Effects of sciatic neurectomy and genetic regulation of bone response to mechanical loading","volume":"25","author":"Kodama","year":"1999","journal-title":"Bone"},{"key":"2024013019210276100_bib11","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1359\/jbmr.2001.16.4.758","article-title":"Genetic control of bone density and turnover: Role of the collagen 1alpha1, estrogen receptor, and vitamin D receptor genes","volume":"16","author":"Brown","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2024013019210276100_bib12","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1002\/jor.1100130510","article-title":"Uniformity of resorptive bone loss induced by disuse","volume":"13","author":"Gross","year":"1995","journal-title":"J Orthop Res"},{"key":"2024013019210276100_bib13","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s002239900653","article-title":"Cancellous bone of the spine is greater in black women","volume":"65","author":"Aloia","year":"1999","journal-title":"Calcif Tissue Int"},{"key":"2024013019210276100_bib14","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1089\/jwh.1.1999.8.609","article-title":"Osteoporosis and African American women","volume":"8","author":"Bohannon","year":"1999","journal-title":"J Womens Health Gend Based Med"},{"key":"2024013019210276100_bib15","first-page":"129","article-title":"Ethnic and genetic differences in susceptibility to osteoporotic fractures","volume":"9","author":"Anderson","year":"1994","journal-title":"Adv Nutr Res"},{"key":"2024013019210276100_bib16","first-page":"S23","article-title":"A new rat model simulating some aspects of space flight","volume":"22","author":"Morey","year":"1979","journal-title":"Physiologist"},{"key":"2024013019210276100_bib17","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/00002142-200210000-00003","article-title":"The Zurich experience: One decade of three-dimensional high-resolution computed tomography","volume":"13","author":"Muller","year":"2002","journal-title":"Top Magn Reson Imaging"},{"key":"2024013019210276100_bib18","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1359\/jbmr.1999.14.7.1167","article-title":"Direct three-dimensional morphometric analysis of human cancellous bone: Microstructural data from spine, femur, iliac crest, and calcaneus","volume":"14","author":"Hildebrand","year":"1999","journal-title":"J Bone Miner Res"},{"key":"2024013019210276100_bib19","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S8756-3282(97)00007-0","article-title":"Three-dimensional methods for quantification of cancellous bone architecture","volume":"20","author":"Odgaard","year":"1997","journal-title":"Bone"},{"key":"2024013019210276100_bib20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/01495739708936692","article-title":"Quantification of bone microarchitecture with the structure model index","volume":"1","author":"Hildebrand","year":"1997","journal-title":"Comput Methods Biomech Biomed Engin"},{"key":"2024013019210276100_bib21","first-page":"21","article-title":"Review of growth plate closure compared with age at sexual maturity and lifespan in laboratory animals","volume":"41","author":"Kilborn","year":"2002","journal-title":"Contemp Top Lab Anim Sci"},{"key":"2024013019210276100_bib22","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1359\/jbmr.2002.17.3.493","article-title":"Noninvasive loading of the murine tibia: An in vivo model for the study of mechanotransduction","volume":"17","author":"Gross","year":"2002","journal-title":"J Bone Miner Res"},{"key":"2024013019210276100_bib23","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1359\/jbmr.2001.16.11.1953","article-title":"Confirmation and fine mapping of chromosomal regions influencing peak bone mass in mice","volume":"16","author":"Klein","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2024013019210276100_bib24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/BF00296061","article-title":"Age-related differences in cross-sectional geometry of the forearm bones in healthy women","volume":"54","author":"Bouxsein","year":"1994","journal-title":"Calcif Tissue Int"},{"key":"2024013019210276100_bib25","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/jbmr.5650070702","article-title":"Relationship between bone mass and rates of bone change at appendicular measurement sites","volume":"7","author":"Davis","year":"1992","journal-title":"J Bone Miner Res"},{"key":"2024013019210276100_bib26","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1093\/aje\/kwf049","article-title":"Natural history of bone loss over 6 years among premenopausal and early postmenopausal women","volume":"156","author":"Bainbridge","year":"2002","journal-title":"Am J Epidemiol"},{"key":"2024013019210276100_bib27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/8756-3282(96)00102-0","article-title":"Low bone mass and fast rate of bone loss at menopause: Equal risk factors for future fracture. A 15-year follow-up study","volume":"19","author":"Riis","year":"1996","journal-title":"Bone"},{"key":"2024013019210276100_bib28","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1007\/s001980200134","article-title":"Baseline BMD and bone loss at distal radius measured by peripheral quantitative computed tomography in peri- and postmenopausal Hong Kong Chinese women","volume":"13","author":"Qin","year":"2002","journal-title":"Osteoporos Int"},{"key":"2024013019210276100_bib29","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1096\/fj.01-0166com","article-title":"The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli","volume":"15","author":"Rubin","year":"2001","journal-title":"FASEB J"},{"key":"2024013019210276100_bib30","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00335-002-3045-y","article-title":"Hierarchical relationship between bone traits and mechanical properties in inbred mice","volume":"14","author":"Jepsen","year":"2003","journal-title":"Mamm Genome"},{"key":"2024013019210276100_bib31","first-page":"S219","article-title":"Tibial cortical strains induced by low-level vibrations are dependent on genetic make-up and frequency of the signal","volume":"18","author":"Karnik","year":"2003","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\/10.1359%2FJBMR.040110","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/19\/4\/607\/56473672\/5650190412.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/19\/4\/607\/56473672\/5650190412.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:06:25Z","timestamp":1710342385000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/19\/4\/607-613\/7592702"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4,1]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2009,12,2]]},"published-print":{"date-parts":[[2004,4,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.040110","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2004,4,1]]},"published":{"date-parts":[[2004,4,1]]}}}