Low levels of plasma IGF-1 inhibit intracortical bone remodeling during aging

Hayden William Courtland, Oran D. Kennedy, Yingjie Wu, Ying Gao, Hui Sun, Mitchell B. Schaffler, Shoshana Yakar

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)1691-1703
Number of pages13
Issue number5
StatePublished - Oct 2013


  • ALSKO mice
  • Aging
  • Bone
  • Endocrine
  • IGF-1
  • Microcomputed tomography

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology


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