{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:04:29Z","timestamp":1787241869976,"version":"build-2736575974"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2010,4,30]],"date-time":"2010-04-30T00:00:00Z","timestamp":1272585600000},"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":[[2010,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Klinefelter syndrome is the most common chromosomal aneuploidy in men (XXY karyotype, 1 in 600 live births) and results in testicular (infertility and androgen deficiency) and nontesticular (cognitive impairment and osteoporosis) deficits. The extent to which skeletal changes are due to testosterone deficiency or arise directly from gene overdosage cannot be determined easily in humans. To answer this, we generated XXY mice through a four-generation breeding scheme. Eight intact XXY and 9 XY littermate controls and 8 castrated XXY mice and 8 castrated XY littermate controls were euthanized at 1 year of age. Castration occurred 6 months prior to killing. A third group of 9 XXY and 11 XY littermates were castrated and simultaneously implanted with a 1-cm Silastic testosterone capsule 8 weeks prior to sacrifice. Tibias were harvested from all three groups and examined by micro\u2013computed tomography and histomorphometry. Blood testosterone concentration was assayed by radioimmunoassay. Compared with intact XY controls, intact androgen-deficient XXY mice had lower bone volume (6.8%\u2009\u00b1\u20091.2% versus8.8%\u2009\u00b1\u20091.7%, mean\u2009\u00b1\u2009SD, p\u2009=\u2009.01) and thinner trabeculae (50\u2009\u00b1\u20094\u2009\u00b5m versus 57\u2009\u00b1\u20095\u2009\u00b5m, p\u2009=\u2009.007). Trabecular separation (270\u2009\u00b1\u200920\u2009\u00b5m versus 270\u2009\u00b1\u200920\u2009\u00b5m) or osteoclast number relative to bone surface (2.4\u2009\u00b1\u20091.0\/mm2 versus 2.7\u2009\u00b1\u20091.5\/mm2) did not differ significantly. Testosterone-replaced XXY mice continued to show lower bone volume (5.5%\u2009\u00b1\u20092.4% versus 8.1%\u2009\u00b1\u20093.5%, p\u2009=\u2009.026). They also exhibited greater trabecular separation (380\u2009\u00b1\u200969\u2009\u00b5m versus 324\u2009\u00b1\u200962\u2009\u00b5m, p\u2009=\u2009.040) but equivalent blood testosterone concentrations (6.3\u2009\u00b1\u20091.8\u2009ng\/mL versus 8.2\u2009\u00b1\u20094.2\u2009ng\/mL, p\u2009=\u2009.28) compared with testosterone-replaced XY littermates. In contrast, castration alone drastically decreased bone volume (p\u2009&amp;lt;\u2009.001), trabecular thickness (p\u2009=\u2009.05), and trabecular separation (p\u2009&amp;lt;\u2009.01) to such a great extent that differences between XXY and XY mice were undetectable. In conclusion, XXY mice replicate many features of human Klinefelter syndrome and therefore are a useful model for studying bone. Testosterone deficiency does not explain the bone phenotype because testosterone-replaced XXY mice show reduced bone volume despite similar blood testosterone levels. \u00a9 2010 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.104","type":"journal-article","created":{"date-parts":[[2010,4,7]],"date-time":"2010-04-07T12:13:59Z","timestamp":1270642439000},"page":"2148-2154","source":"Crossref","is-referenced-by-count":26,"title":["Genetic and hormonal control of bone volume, architecture, and remodeling in XXY mice"],"prefix":"10.1093","volume":"25","author":[{"given":"Peter Y","family":"Liu","sequence":"first","affiliation":[{"name":"Endocrine and Metabolic Research Program, Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia"},{"name":"Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute (LA BioMed) at Harbor-UCLA Medical Center, Torrance, CA, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Erkkila","sequence":"additional","affiliation":[{"name":"Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland"},{"name":"Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute (LA BioMed) at Harbor-UCLA Medical Center, Torrance, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Bone Biology Research Program, ANZAC Institute of Medical Research, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus J","family":"Seibel","sequence":"additional","affiliation":[{"name":"Bone Biology Research Program, ANZAC Institute of Medical Research, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute (LA BioMed) at Harbor-UCLA Medical Center, Torrance, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald S","family":"Swerdloff","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute (LA BioMed) at Harbor-UCLA Medical Center, Torrance, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin R","family":"Dunstan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Sydney, Sydney, Australia"},{"name":"Bone Biology Research Program, ANZAC Institute of Medical Research, University of Sydney, Sydney, 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