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The relationship of 25-hydroxyvitamin D values and risk of fracture: a population-based retrospective cohort study

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Abstract

Summary

Our study investigates 25-hydroxyvitamin D levels and fracture risk using population-level data. 25-Hydroxyvitamin D values < 12, 12–19, and > 50 ng/mL were not associated with increased risk of fractures overall compared with values 20–50 ng/mL. Severely low levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist.

Introduction

Studies of the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and fracture risk have been inconsistent. We hypothesized that high 25(OH)D concentrations (> 50 ng/mL) would be associated with increased risk of fracture.

Methods

We identified all adult patients living in Olmsted County, Minnesota, between January 1, 2005 and December 31, 2011, who had at least one 25(OH)D measurement. Fracture outcomes were retrieved starting 30 days after 25(OH)D measurement and until patients’ final clinical visit as an Olmsted County resident, December 31, 2014, or death. Data were analyzed using Cox proportional hazard regression.

Results

Of 11,002 individuals with a 25(OH)D measurement, 5.8% had a 25(OH)D value ˂ 12 ng/mL, and 5.1% had a value > 50 ng/mL. Compared with subjects with 25(OH)D values 20–50 ng/mL (reference group), values < 12, 12–19, and > 50 ng/mL displayed no association with overall fracture risk. After adjusting for a prior diagnosis of osteoporosis/osteopenia, only individuals with values ˂ 12 ng/mL had increased risk of any osteoporotic fracture (aHR = 1.41; 95% CI 1.05–1.89) and wrist fracture (aHR = 2.11; 95% CI 1.27–3.48) compared with the reference group. Compared with the reference group, values ˂ 12 ng/mL were associated with increased risk of any fracture (aHR = 1.35; 95% CI 1.01–1.80), osteoporotic fracture (aHR = 2.18; 95% CI 1.44–3.31), and wrist fracture (aHR = 2.39; 95% CI 1.19–4.81) in subjects without a prior diagnosis of osteoporosis/osteopenia, but not in those with a prior diagnosis of osteoporosis/osteopenia.

Conclusion

Severely low 25(OH)D levels may be associated with increased risk of osteoporotic fracture, particularly of the wrist, but 25(OH)D values > 50 ng/mL were not associated with increased fracture risk.

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Funding

This study was funded by CTSA Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences. This study was also made possible using the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG034676. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Mayo Clinic Alix School of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    A. J. Aul

  2. Department of Internal Medicine, Mayo Clinic, 4500 San Pablo Road S, Jacksonville, FL, 32224, USA

    D. V. Dudenkov

  3. Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    K. C. Mara

  4. Department of Community Pediatric and Adolescent Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Y. J. Juhn & C. I. Wi

  5. Department of Family Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    J. A. Maxson & T. D. Thacher

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Correspondence to T. D. Thacher.

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The study was approved by the Mayo Clinic Institutional Review Board, and all included records had research authorization for retrospective chart review.

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Aul, A.J., Dudenkov, D.V., Mara, K.C. et al. The relationship of 25-hydroxyvitamin D values and risk of fracture: a population-based retrospective cohort study. Osteoporos Int 31, 1787–1799 (2020). https://doi.org/10.1007/s00198-020-05436-7

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