{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:27:42Z","timestamp":1787243262925,"version":"build-2736575974"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T00:00:00Z","timestamp":1439164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008333","name":"University of Alabama at Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008333","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Advanced aging is associated with increased risk of bone fracture, especially within the vertebrae, which exhibit significant reductions in trabecular bone structure. Aging is also associated with a reduction in circulating levels of insulin-like growth factor (IGF-1). Studies have suggested that the reduction in IGF-1 compromises healthspan, whereas others report that loss of IGF-1 is beneficial because it increases healthspan and lifespan. To date, the effect of decreases in circulating IGF-1 on vertebral bone aging has not been thoroughly investigated. Here, we delineate the consequences of a loss of circulating IGF-1 on vertebral bone aging in male and female Igff\/f mice. IGF-1 was reduced at multiple specific time points during the mouse lifespan: early in postnatal development (crossing albumin\u2013cyclic recombinase [Cre] mice with Igff\/f mice); and in early adulthood and in late adulthood using hepatic-specific viral vectors (AAV8-TBG-Cre). Vertebrae bone structure was analyzed at 27 months of age using micro\u2013computed tomography (\u03bcCT) and quantitative bone histomorphometry. Consistent with previous studies, both male and female mice exhibited age-related reductions in vertebral bone structure. In male mice, reduction of circulating IGF-1 induced at any age did not diminish vertebral bone loss. Interestingly, early-life loss of IGF-1 in females resulted in a 67% increase in vertebral bone volume fraction, as well as increased connectivity density and increased trabecular number. The maintenance of bone structure in the early-life IGF-1\u2013deficient females was associated with increased osteoblast surface and an increased ratio of osteoprotegerin\/receptor-activator of NF-\u03baB-ligand (RANKL) levels in circulation. Within 3 months of a loss of IGF-1, there was a 2.2-fold increase in insulin receptor expression within the vertebral bones of our female mice, suggesting that local signaling may compensate for the loss of circulating IGF-1. Together, these data suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. \u00a9 2015 American Society for Bone and Mineral Research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.2689","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T18:52:02Z","timestamp":1439232722000},"page":"443-454","source":"Crossref","is-referenced-by-count":43,"title":["IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms"],"prefix":"10.1093","volume":"31","author":[{"given":"Nicole M","family":"Ashpole","sequence":"first","affiliation":[{"name":"Reynolds Oklahoma Center on AgingDonald W. Reynolds Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn C","family":"Herron","sequence":"additional","affiliation":[{"name":"Department of Immunology\/Rheumatology\/Allergy MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C","family":"Mitschelen","sequence":"additional","affiliation":[{"name":"Reynolds Oklahoma Center on AgingDonald W. Reynolds Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Farley","sequence":"additional","affiliation":[{"name":"Reynolds Oklahoma Center on AgingDonald W. Reynolds Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreemathi","family":"Logan","sequence":"additional","affiliation":[{"name":"Reynolds Oklahoma Center on AgingDonald W. Reynolds Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yan","sequence":"additional","affiliation":[{"name":"Reynolds Oklahoma Center on AgingDonald W. Reynolds Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Ungvari","sequence":"additional","affiliation":[{"name":"Reynolds Oklahoma Center on AgingDonald W. Reynolds Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik L","family":"Hodges","sequence":"additional","affiliation":[{"name":"Reynolds Oklahoma Center on AgingDonald W. Reynolds Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Csiszar","sequence":"additional","affiliation":[{"name":"Reynolds Oklahoma Center on AgingDonald W. Reynolds Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Ikeno","sequence":"additional","affiliation":[{"name":"Department of Pathology Barshop Institute for Longevity and Aging StudiesUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Beth","family":"Humphrey","sequence":"additional","affiliation":[{"name":"Department of Veterans' AffairsOklahoma CityOKUSA"},{"name":"Department of Immunology\/Rheumatology\/Allergy MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E","family":"Sonntag","sequence":"additional","affiliation":[{"name":"Reynolds Oklahoma Center on AgingDonald W. Reynolds Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,10]]},"reference":[{"issue":"3","key":"2024021014190737100_jbmr2689-bib-0001","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1359\/jbmr.061113","article-title":"Incidence and economic burden of osteoporosis-related fractures in the United States, 2005\u20132025","volume":"22","author":"Burge","year":"2007","journal-title":"J Bone Miner Res"},{"issue":"34","key":"2024021014190737100_jbmr2689-bib-0002","doi-asserted-by":"crossref","first-page":"9290","DOI":"10.1016\/j.biomaterials.2014.07.051","article-title":"The influence of age on adaptive bone formation and bone resorption","volume":"35","author":"Birkhold","year":"2014","journal-title":"Biomaterials"},{"key":"2024021014190737100_jbmr2689-bib-0003","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1007\/s00198-002-1340-9","article-title":"Reduced bone formation and increased bone resorption: rational targets for the treatment of osteoporosis","author":"Seeman","year":"2003","journal-title":"Osteoporos Int"},{"key":"2024021014190737100_jbmr2689-bib-0004","first-page":"iv2","article-title":"Structural basis of growth-related gain and age-related loss of bone strength","author":"Seeman","year":"2008","journal-title":"Rheumatology (Oxford)"},{"issue":"1","key":"2024021014190737100_jbmr2689-bib-0005","doi-asserted-by":"crossref","first-page":"41","DOI":"10.11005\/jbm.2014.21.1.41","article-title":"Role of osteocyte-derived insulin-like growth factor i in developmental growth, modeling, remodeling, and regeneration of the bone","volume":"21","author":"Sheng","year":"2014","journal-title":"J Bone Metab"},{"issue":"2","key":"2024021014190737100_jbmr2689-bib-0006","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00109-013-1084-3","article-title":"Function of matrix IGF-1 in coupling bone resorption and formation","volume":"92","author":"Crane","year":"2014","journal-title":"J Mol Med"},{"key":"2024021014190737100_jbmr2689-bib-0007","doi-asserted-by":"crossref","first-page":"93S","DOI":"10.1016\/8756-3282(95)00186-H","article-title":"The insulin-like growth factor system and the coupling of formation to resorption","author":"Hayden","year":"1995","journal-title":"Bone"},{"issue":"11)","key":"2024021014190737100_jbmr2689-bib-0008","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.tem.2012.03.008","article-title":"Estrogen and the skeleton","volume":"23","author":"Khosla","year":"2012","journal-title":"Trends Endocrinol Metab"},{"issue":"2)","key":"2024021014190737100_jbmr2689-bib-0009","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/jcp.22159","article-title":"Regulation of adult bone turnover by sex steroids","volume":"224","author":"Frenkel","year":"2010","journal-title":"J Cell Physiol"},{"key":"2024021014190737100_jbmr2689-bib-0010","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1210\/rp.57.1.385","article-title":"Sex steroids and bone","volume":"57","author":"Manolagas","year":"2002","journal-title":"Recent Prog Horm Res"},{"issue":"12)","key":"2024021014190737100_jbmr2689-bib-0011","first-page":"4257","article-title":"Association between insulin-like growth factor I and bone mineral density in older women and men: the Framingham Heart Study","volume":"83","author":"Langlois","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"issue":"1)","key":"2024021014190737100_jbmr2689-bib-0012","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s002230020048","article-title":"Bone mineral density in femoral neck is positively correlated to circulating insulin-like growth factor (IGF)-I and IGF-binding protein (IGFBP)-3 in Swedish men","volume":"70","author":"Gillberg","year":"2002","journal-title":"Calcif Tissue Int"},{"issue":"6)","key":"2024021014190737100_jbmr2689-bib-0013","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1530\/eje.0.1380627","article-title":"Gender-specific relationship between serum free and total IGF-I and bone mineral density in elderly men and women","volume":"138","author":"Janssen","year":"1998","journal-title":"Eur J Endocrinol"},{"issue":"4)","key":"2024021014190737100_jbmr2689-bib-0014","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s00223-003-0090-9","article-title":"Insulin-like growth factor I is a determinant of hip bone mineral density in men less than 60 years of age: MINOS study","volume":"74","author":"Szulc","year":"2004","journal-title":"Calcif Tissue Int"},{"issue":"4)","key":"2024021014190737100_jbmr2689-bib-0015","first-page":"392","article-title":"body mass index, current smoking history, and serum insulin-like growth factor-I levels associated with bone mineral density in middle-aged Korean men. 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