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The associations of markers of endothelial dysfunction with hip fracture risk

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Abstract

Summary

Endothelial dysfunction underlies the development of atherosclerotic vascular disease, which in turn is associated with osteoporotic fractures. Here, we examined the association of two markers of endothelial dysfunction with incident hip fracture risk in older adults but found no statistically significant associations between them.

Purpose/Introduction

Endothelial dysfunction underlies the development of atherosclerotic vascular disease. Vascular disease, in turn, is associated with the risk of osteoporotic fractures, such as hip fractures. Here, we examine whether two measures of endothelial dysfunction are related to hip fracture risk.

Methods

Participants for this study were 2792 individuals (mean age 78.6 years) who had flow-mediated dilation (FMD) measured after ischemia in the forearm and 2255 adults (mean age 73.3 years) with measured soluble intercellular adhesion molecule (siCAM) levels, a constitutive endothelial cell membrane protein associated with the initiation of atherosclerosis. Mean follow-up was 9.7 and 11.7 years, respectively. There were 375 and 265 incident hip fractures, respectively, in each group.

Results

In Cox proportional hazards models, there was no significant association between FMD response and incident hip fracture (HR per 1% higher FMD was 0.98 [0.93, 1.04]; p = 0.44). In exploratory analyses, when data were examined dichotomously, participants in the lowest 80% of FMD (≤ 4.5%) had an adjusted 1.29 (0.98, 1.68; p = 0.067) higher hazard of hip fracture compared to participants in the upper 20% of FMD change. There were no significant associations between siCAM and incident hip fracture whether examined as a continuous or dichotomized variable.

Conclusions

Among older adults, two measures of endothelial dysfunction were not significantly associated with hip fracture risk. There was a trend for higher fracture risk with lower FMD.

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Data Availability

Raw data is available upon reasonable request.

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Acknowledgements

A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org.

Funding

This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and 75N92021D00006 and grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 and K24AG065525 from the National Institute on Aging (NIA).

Author information

Authors and Affiliations

  1. Division of Endocrinology, Kaiser Permanente of Georgia, 3650 Steve Reynolds Blvd, Duluth, GA, 30096, USA

    Joshua I. Barzilay

  2. Division of Endocrinology, Emory University School of Medicine, Atlanta, GA, USA

    Joshua I. Barzilay

  3. Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA

    Petra Buzkova

  4. Geriatric Research Education and Clinical Center, VA Health Care System, Minneapolis, MN, USA

    Howard A. Fink

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

    Howard A. Fink

  6. Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Jane A. Cauley

  7. Division of Rheumatology, Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA

    Laura Carbone

  8. Division of Rheumatology, Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA

    Rachel Elam

  9. Department of Medicine, University of California, Davis, Sacramento, CA, USA

    John A. Robbins

  10. Department of Medicine, Cardiovascular Division, Washington University in Saint Louis School of Medicine, Saint Louis, MO, USA

    Phyllis Stein

  11. Geriatric Medicine, Hennepin Healthcare, Minneapolis, MN, USA

    Kerry Sheets

  12. Division of Nephrology, Department of Internal Medicine, Carver College of Medicine, Iowa City, IA, USA

    Diana Jalal

  13. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Brookline, MA, USA

    Kenneth J. Mukamal

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  1. Joshua I. Barzilay
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  2. Petra Buzkova
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Corresponding author

Correspondence to Joshua I. Barzilay.

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Barzilay, J.I., Buzkova, P., Fink, H.A. et al. The associations of markers of endothelial dysfunction with hip fracture risk. Arch Osteoporos 18, 39 (2023). https://doi.org/10.1007/s11657-023-01226-w

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