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No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene

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Abstract

Summary

Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men.

Introduction

There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007.

Methods

The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture.

Results

Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE = 0.83; 95 % CI, 0.63–1.08) or osteoporotic fracture (OR per 10 g RE = 0.95; 95 % CI 0.64–1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g = 0.89; 95 % CI 0.81–0.98) and osteoporotic fracture (OR per 10 g = 0.84; 95 % CI 0.72–0.97).

Conclusions

This study observed no increases in fracture risk after long-term supplementation with high doses of retinol and/or beta-carotene.

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Acknowledgments

The authors wish to express their sincere thanks to all participants in the Vitamin A Program. We are also very grateful to Lynne Watts, Naomi Hammond, Meralyn Pearce and Diane Jacoby who collected data for this study; Jan Sleith for data entry and data cleaning; Robin Mina who oversaw database management and staff from the Perth Chest Clinic. This study was funded by project grants from the National Health and Medical Research Council of Australia (project ID Ambrosini 458608, Musk 403930 and Musk 139047), the Western Australian Department of Health and the Worker’s Compensation and Rehabilitation Commission of Western Australia.

Conflicts of interest

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Authors and Affiliations

  1. School of Population Health, The University of Western Australia, Perth, WA, Australia

    G. L. Ambrosini, A. P. Bremner, N. J. Olsen & A. W. Musk

  2. Western Australian Institute for Medical Research, The University of Western Australia, Perth, WA, Australia

    A. Reid

  3. Menzies School of Health Research, Institute of Advanced Studies, Charles Darwin University, Darwin, NT, Australia

    D. Mackerras

  4. Western Australian Centre for Health and Ageing, The University of Western Australia, Perth, WA, Australia

    H. Alfonso

  5. Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia

    N. J. Olsen & A. W. Musk

  6. Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, PO Box 855, West Perth, Perth, WA, Australia

    N. H. de Klerk

Authors
  1. G. L. Ambrosini
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  2. A. P. Bremner
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  3. A. Reid
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  4. D. Mackerras
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  5. H. Alfonso
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  6. N. J. Olsen
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  7. A. W. Musk
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  8. N. H. de Klerk
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Corresponding author

Correspondence to N. H. de Klerk.

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Ambrosini, G.L., Bremner, A.P., Reid, A. et al. No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene. Osteoporos Int 24, 1285–1293 (2013). https://doi.org/10.1007/s00198-012-2131-6

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  • DOI: https://doi.org/10.1007/s00198-012-2131-6

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