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Association of DPP-4 activity with BMD, body composition, and incident hip fracture: the Cardiovascular Health Study

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Abstract

Summary

There was no association of plasma DPP-4 activity levels with bone mineral density (BMD), body composition, or incident hip fractures in a cohort of elderly community-dwelling adults.

Introduction

Dipeptidyl peptidase IV (DPP-4) inactivates several key hormones including those that stimulate postprandial insulin secretion, and DPP-4 inhibitors (gliptins) are approved to treat diabetes. While DPP-4 is known to modulate osteogenesis, the relationship between DPP-4 activity and skeletal health is uncertain. The purpose of the present study was to examine possible associations between DPP-4 activity in elderly subjects enrolled in the Cardiovascular Health Study (CHS) and BMD, body composition measurements, and incident hip fractures.

Methods

All 1536 male and female CHS participants who had evaluable DXA scans and plasma for DPP-4 activity were included in the analyses. The association between (1) BMD of the total hip, femoral neck, lumbar spine, and total body; (2) body composition measurements (% lean, % fat, and total body mass); and (3) incident hip fractures and plasma levels of DPP-4 activity were determined.

Results

Mean plasma levels of DPP-4 activity were significantly higher in blacks (227 ± 78) compared with whites (216 ± 89) (p = 0.04). However, there was no significant association of DPP-4 activity with age or gender (p ≥ 0.14 for both). In multivariable adjusted models, there was no association of plasma DPP-4 activity with BMD overall (p ≥ 0.55 for all) or in gender stratified analyses (p ≥ 0.23). There was also no association of DPP-4 levels and incident hip fractures overall (p ≥ 0.24) or in gender stratified analyses (p ≥ 0.39).

Conclusion

Plasma DPP-4 activity, within the endogenous physiological range, was significantly associated with race, but not with BMD, body composition, or incident hip fractures in elderly community-dwelling subjects.

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Acknowledgements

This work was supported by the National Institutes of Health (NIH) for the Cardiovascular Health Study (CHS) components (LDC, PB, HAF, and JAR) by the National Heart, Lung, and Blood Institute (NHLBI) with additional contribution from the National Institute of Neurological Disorders and Stroke (contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC55222N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants HL094555 and 080295); additional support provided by the National Institute on Aging (NIA) (RO1AG023629 (CHS—LDC, PB, HAF, and JAR), P01 AG036675—CMI, WDH), and Augusta University Pilot Study Research Program (WDH/LC) and supported in part by the Department of Veterans Affairs (Merit Award 1I01CX000930-01—WDH). The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government.

Author information

Authors and Affiliations

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

    L. D. Carbone, M. Bethel & W. D. Hill

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

    L. D. Carbone, M. Bethel & C. M. Isales

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

    P. Bůžková

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

    H. A. Fink

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

    H. A. Fink

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

    H. A. Fink

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

    H. A. Fink

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

    J. 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

    C. M. Isales & W. D. Hill

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

    C. M. Isales & W. 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

    C. M. Isales

  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, b1459 Laney-Walker Blvd., Augusta, GA, 30912-2000, USA

    W. D. Hill

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  1. L. D. Carbone
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  2. P. Bůžková
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  7. W. D. Hill
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Corresponding author

Correspondence to W. D. Hill.

Ethics declarations

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.

Conflicts of interest

Authors Laura Carbone, Petra Bůžková, Howard Fink, John Robbins, Monique Bethel, and Carlos Isales declare that they have no conflict of interest. William Hill is an inventor on provisional patent U.S.S.N. 61/712/708, Publication no. US-2014-0288010-A1 titled “Compositions and Methods for Increasing Stem Cell Survival.” This is not a financial conflict.

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Carbone, L.D., Bůžková, P., Fink, H.A. et al. Association of DPP-4 activity with BMD, body composition, and incident hip fracture: the Cardiovascular Health Study. Osteoporos Int 28, 1631–1640 (2017). https://doi.org/10.1007/s00198-017-3916-4

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  • DOI: https://doi.org/10.1007/s00198-017-3916-4

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