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Biochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study

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Abstract

Summary

The relationships of osteocalcin (OC) and C-telopeptide of type I collagen (CTX) with long-term incidence of hip fracture were examined in 1680 post-menopausal women from a population-based study. CTX, but not OC, levels were associated with incident hip fracture in these participants, a relationship characterized by an inverted U-shape.

Introduction

We sought to investigate the relationships of OC, a marker of bone formation, and CTX, a marker of bone resorption, with long-term incidence of hip fracture in older women.

Methods

We included 1680 women from the population-based Cardiovascular Health Study (mean [SD] age 74.5 [5.0] years). The longitudinal association of both markers with incidence of hip fracture was examined using multivariable Cox models.

Results

During a median follow-up of 12.3 years, 288 incident hip fractures occurred. Linear spline analysis did not demonstrate an association between OC levels and incident hip fracture. By contrast, increasing levels of CTX up to the middle-upper range were associated with a significantly greater risk of hip fracture (HR = 1.52 per SD increment, 95% CI = 1.10–2.09), while further increases were associated with a marginally non-significant lower risk (HR = 0.80 per SD increment, 95% CI = 0.63–1.01), after full adjustment for potential confounders. In analyses of quartiles, CTX exhibited a similar inverted U-shaped relationship with incident fracture after adjustment, with a significant association observed only for the comparison of quartile 3 to quartile 1 (HR = 1.63, 95% CI = 1.10–2.43). In a subset with available measures, both OC and CTX were inversely associated with bone mineral density of the hip.

Conclusion

CTX, but not OC, levels were associated with incident hip fracture in post-menopausal women, a relationship characterized by an inverted U-shape. These findings highlight the complex relationship of bone turnover markers with hip fracture risk.

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Funding

This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, 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 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. D.M. was supported by The Glorney-Raisbeck Fellowship Program, Corlette Glorney Foundation, and The New York Academy of Medicine. J.R.K. was supported by K24HL135413 from the NHLBI.

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Authors and Affiliations

  1. New York University School of Medicine, New York, NY, USA

    D. Massera

  2. Albert Einstein College of Medicine, Bronx, NY, USA

    S. Xu & X. Xue

  3. College of Physicians and Surgeons, Columbia University, New York, NY, USA

    M. D. Walker

  4. University of Miami, Miami, FL, USA

    R. J. Valderrábano

  5. Beth Israel Deaconess Medical Center, Boston, MA, USA

    K. J. Mukamal

  6. University of California San Diego, San Diego, CA, USA

    J. H. Ix

  7. New York Academy of Medicine, New York, NY, USA

    D. S. Siscovick

  8. University of Vermont, Burlington, VT, USA

    R. P. Tracy

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

    J. A. Robbins

  10. University of Washington, Seattle, WA, USA

    M. L. Biggs

  11. Cardiology Section, San Francisco Veterans Affairs Health Care System and University of California San Francisco, 4150 Clement St, San Francisco, CA, 94121, USA

    J. R. Kizer

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  1. D. Massera
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  2. S. Xu
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  12. J. R. Kizer
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Corresponding author

Correspondence to J. R. Kizer.

Ethics declarations

All field centers and the CHS Coordinating Center received institutional review board approval for the study and participants gave informed consent.

Conflicts of interest

Jorge R. Kizer reports stock ownership in Amgen, Bristol-Myers Squibb, Gilead Sciences, Merck, Johnson and Johnson, and Pfizer. Daniele Massera, Shuo Xu, Marcella D. Walker, Rodrigo J. Valderrábano, Kenneth J. Mukamal, Joachim H. Ix, David S. Siscovick, Russell P. Tracy, John A. Robbins, Mary L. Biggs, and Xiaonan Xue declare that they have no conflict of interest.

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Massera, D., Xu, S., Walker, M.D. et al. Biochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study. Osteoporos Int 30, 1755–1765 (2019). https://doi.org/10.1007/s00198-019-05043-1

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