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Association of Plasma SDF-1 with Bone Mineral Density, Body Composition, and Hip Fractures in Older Adults: The Cardiovascular Health Study

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Abstract

Aging is associated with an increase in circulating inflammatory factors. One, the cytokine stromal cell-derived factor 1 (SDF-1 or CXCL12), is critical to stem cell mobilization, migration, and homing as well as to bone marrow stem cell (BMSC), osteoblast, and osteoclast function. SDF-1 has pleiotropic roles in bone formation and BMSC differentiation into osteoblasts/osteocytes, and in osteoprogenitor cell survival. The objective of this study was to examine the association of plasma SDF-1 in participants in the cardiovascular health study (CHS) with bone mineral density (BMD), body composition, and incident hip fractures. In 1536 CHS participants, SDF-1 plasma levels were significantly associated with increasing age (p < 0.01) and male gender (p = 0.04), but not with race (p = 0.63). In multivariable-adjusted models, higher SDF-1 levels were associated with lower total hip BMD (p = 0.02). However, there was no significant association of SDF-1 with hip fractures (p = 0.53). In summary, circulating plasma levels of SDF-1 are associated with increasing age and independently associated with lower total hip BMD in both men and women. These findings suggest that SDF-1 levels are linked to bone homeostasis.

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Acknowledgements

This work was supported by contracts and awards to the Cardiovascular Health Study (CHS) from the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS) including contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC55222N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086, and grants HL094555 and 080295; additional support provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. Additional support was provided by P01AG036675 from the NIA (WDH/MWH), the Augusta University Pilot Study Research Program (WDH/LC), and by 1I01CX000930 from the Department of Veterans Affairs (WDH). The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government.

Authors’ Roles

LDC: conceiving and designing the study, interpretation of the data, and drafting of the manuscript. PB: statistical analyses and critical review of the manuscript. HAF: critical review of the manuscript, designing the study, and interpretation of the data. JAR: designing the study, interpretation of the data, critical review of the manuscript, and funding support. MB: interpretation of the data and critical review of the manuscript. MWH: critical review of the manuscript and interpretation of data. WDH: conceiving and designing the study, interpretation of the data, performance of SDF-1 laboratory measurements, and critical review of the manuscript.

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Authors and Affiliations

  1. Charlie Norwood Veterans Affairs Medical Center, Augusta, GA, USA

    Laura D. Carbone, Monique Bethel & William D. Hill

  2. Department of Medicine, Medical College of Georgia, Augusta University (formerly Georgia Regents University and Georgia Health Sciences University), Augusta, GA, USA

    Laura D. Carbone & Monique Bethel

  3. Department of Biostatistics, University of Washington, Seattle, WA, USA

    Petra Bůžková

  4. Veterans Affairs Health Care System, Geriatric Research Education & Clinical Center, Minneapolis, MN, USA

    Howard A. Fink

  5. Veterans Affairs Health Care System, Center for Chronic Disease Outcomes Research, Minneapolis, MN, USA

    Howard A. Fink

  6. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Howard A. Fink

  7. Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA

    Howard A. Fink

  8. Department of Medicine, University of California – Davis, Sacramento, CA, USA

    John A. Robbins

  9. Institute for Regenerative and Reparative Medicine, Medical College of Georgia, Augusta University (formerly Georgia Regents University and Georgia Health Sciences University), Augusta, GA, USA

    Mark W. Hamrick & William D. Hill

  10. Department of Orthopaedic Surgery, Augusta University (formerly Georgia Regents University and Georgia Health Sciences University), Augusta, GA, USA

    Mark W. Hamrick & William D. Hill

  11. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University (formerly Georgia Regents University and Georgia Health Sciences University), Augusta, GA, USA

    Mark W. Hamrick

  12. Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University (formerly Georgia Regents University and Georgia Health Sciences University), Sanders Research Building, CB1119 1459 Laney-Walker Blvd., Augusta, Georgia, 30912-2000, USA

    Mark W. Hamrick & William D. Hill

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  1. Laura D. Carbone
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Correspondence to William D. Hill.

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Conflict of interest

Laura D. Carbone, Petra Bůžková, Howard A. Fink, John A. Robbins, Monique Bethel, Mark W. Hamrick and William D. Hill declare that they have no conflict of interest.

Disclosures

William Hill has received a Utility Patent. GRU OTT 2013-26 U.S.S.N. 61/712/708 filed 2-22-2013. Publication# US-2014-0288010-A1. The application was published on September 25, 2014. “Compositions and Methods for Increasing Stem Cell Survival” By William D. Hill, Samuel Herberg, & Sudharsan Periyasami-Thandavan. Describing SDF-1’s role in enhancing BMSC autophagy and blocking apoptosis and potential clinical applications, and including inhibition of DPP4 to enhance SDF-1 activity levels.

Human and animal rights and Informed consent

The institutional review board (IRB) at each site approved the CHS methods, and all participants gave written informed consent. Augusta University’s Office of Human Research Protection Assurance approved the use of human plasma samples previously collected as part of the CHS. No animals were used.

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Carbone, L.D., Bůžková, P., Fink, H.A. et al. Association of Plasma SDF-1 with Bone Mineral Density, Body Composition, and Hip Fractures in Older Adults: The Cardiovascular Health Study. Calcif Tissue Int 100, 599–608 (2017). https://doi.org/10.1007/s00223-017-0245-8

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  • DOI: https://doi.org/10.1007/s00223-017-0245-8

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