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

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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.

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Acknowledgments

The authors would like to thank Dr. Boisclair YR (Department of Animal Science, Cornell University, Ithaca, New York 14853, USA) for creation of the original ALSKO line.

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Bone Diseases, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Hayden-William Courtland, Yingjie Wu, Ying Gao, Hui Sun & Shoshana Yakar

  2. Department of Biomedical Engineering, City College of New York, CUNY, New York, NY, 10031, USA

    Oran D. Kennedy & Mitchell B. Schaffler

  3. David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, 345 East 24th Street, New York, NY, 10010-4086, USA

    Yingjie Wu, Hui Sun & Shoshana Yakar

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  1. Hayden-William Courtland
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  2. Oran D. Kennedy
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  4. Ying Gao
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  5. Hui Sun
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  7. Shoshana Yakar
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Correspondence to Shoshana Yakar.

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Courtland, HW., Kennedy, O.D., Wu, Y. et al. Low levels of plasma IGF-1 inhibit intracortical bone remodeling during aging. AGE 35, 1691–1703 (2013). https://doi.org/10.1007/s11357-012-9469-8

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  • DOI: https://doi.org/10.1007/s11357-012-9469-8

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