title: Low levels of plasma IGF-1 inhibit intracortical bone remodeling during aging.
abstract: Studies linking insulin-like growth factor-1 (IGF-1) to age-related bone loss in humans have been reported but remain only correlative. In this investigation, we characterized the bone phenotype of aged WT C57BL/6J male mice in comparison to that of C57BL/6J mice with reduced serum IGF-1 levels arising from an igfals gene deletion (ALS knockout (ALSKO)). During the aging process, WT mice showed an increase in fat mass and decrease lean mass while ALSKO mice had stable lean and fat mass values. Skeletal analyses of femora from WT mice revealed an expansion of the marrow area and a significant accumulation of intracortical porosity associated with increased intracortical remodeling. In contrast, ALSKO mice showed only small age-related declines in the amount of cortical bone tissue and minimal intracortical porosity, at 2 years of age. Accordingly, mechanical tests of femora from 2-year-old WT mice revealed reduced stiffness and maximal load when compared to bones from ALSKO mice. We show here that lifelong reductions in serum IGF-1 compromise skeletal size in development leading to slender bones; they are also associated with decreased intracortical bone remodeling and preservation of bone strength during aging.
authors.affiliation: Division of Endocrinology, Diabetes and Bone Diseases, Mount Sinai School of Medicine, New York, NY, 10029, USA.
authors.forename: Hayden-William
authors.initials: HW
authors.lastname: Courtland
authors.forename: Oran D
authors.initials: OD
authors.lastname: Kennedy
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Schaffler
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005269:Femur / Q000254:growth & development; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010024:Osteoporosis / Q000097:blood* / Q000473:pathology
chemical_list: D007334:Insulin-Like Growth Factor I