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Associations of hemoglobin and change in hemoglobin with risk of incident hip fracture in older men and women: the cardiovascular health study

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Abstract

Summary

In a multi-site longitudinal cohort study, decreasing hemoglobin was associated with increased hip fracture risk in men. Anemia was associated with hip fracture in men and in African American women. Decreasing hemoglobin may be a marker of progressing bone fragility, making its serial measurement useful for fracture risk stratification.

Introduction

Hematopoiesis and bone health are interdependent. Anemia has been associated with risk of fracture in humans. To further elucidate this relationship, we hypothesized that decreasing hemoglobin could indicate defective hematopoiesis and would also predict fracture risk.

Methods

We performed a prospective analysis from study baseline (1992) of the Cardiovascular Health Study, a multi-site longitudinal cohort study. A total of 4670 men and women, ages >65 years, who were able to consent and not institutionalized or wheelchair bound, had hemoglobin (Hb) measured in 1992. For 4006 subjects, Hb change from 1989 to 1992 was annualized and divided into sex-specific quartiles. Incident hip fractures were verified against Medicare claims data during a median follow-up of 11.8 years.

Results

Nested Cox proportional-hazard models estimated association of hip fracture with anemia (men Hb <13 g/dL, women Hb <12 g/dL) and separately, greatest Hb decrease (versus others). Anemia was associated with increased hip fracture risk in all men (HR 1.59; 95% CI 1.01–2.50) and African American women (HR 3.21; 95% CI 1.07–9.63). In men, an annualized Hb loss of >0.36 g/dL/year was associated with a higher risk of hip fracture (HR 1.67; 95% CI 1.10–2.54), which was lessened by anemia at the start of fracture follow-up (HR 1.53; 95% CI 0.99–2.39).

Conclusions

Decreasing Hb may be an early marker for subsequent hip fracture risk in men, which may be less informative once an anemia threshold is crossed. Only African American women with anemia had increased hip fracture risk, suggesting a race difference in this relationship.

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Data availability

BioLINCC CHS data package was last updated in June of 2016; researchers can request data but must be registered on the CHS website.

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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. The content is solely our responsibility and does not necessarily represent the official views of the National Institute of Health.

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Author notes

  1. R.J. Valderrábano, J.Y. Wu and J.S. Lee contributed equally to this work.

Authors and Affiliations

  1. University of Miami Miller School of Medicine, P.O. Box 016960 (D-56), Miami, FL, 33101, USA

    R.J. Valderrábano

  2. Division of Endocrinology, Stanford University School of Medicine, 300 Pasteur Dr., S-025, Stanford, CA, 94305, USA

    R.J. Valderrábano, P.-Y. Chang, J.Y. Wu & J.S. Lee

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

    P. Buzkova

  4. School of Medicine, University of California, Davis, CA, USA

    P.-Y. Chang & J.A. Robbins

  5. Department of Medicine and Department of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA

    N.A. Zakai

  6. GRECC, Veteran Affairs Health Care System, Minneapolis, MN, USA

    H.A. Fink

  7. Palo Alto Veteran Affairs Health Care System, Palo Alto, CA, USA

    J.S. Lee

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for the Cardiovascular Health Study group

Contributions

Study design: RV, JW, and JL. Study conduct: HF and JR. Data collection: HF and JR. Data analysis: PB. Data interpretation: RV, PC, HF, JR, JW, and JL. Drafting manuscript: RV. Revising manuscript content: RV, PB, PC, NZ, HF, JW, JL. Approving final version of manuscript: RV, PB, PC, NZ, HF, JR, JW, JL. RV takes responsibility for the integrity of the data analysis.

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Correspondence to R.J. Valderrábano or J.Y. Wu.

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Valderrábano, R., Buzkova, P., Chang, PY. et al. Associations of hemoglobin and change in hemoglobin with risk of incident hip fracture in older men and women: the cardiovascular health study. Osteoporos Int 32, 1669–1677 (2021). https://doi.org/10.1007/s00198-021-05873-y

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