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Calcium and vitamin D supplementation and incident rheumatoid arthritis: the Women’s Health Initiative Calcium plus Vitamin D trial

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Abstract

To determine whether calcium plus vitamin D supplementation (CaD) affects incidence of rheumatoid arthritis (RA). Participants enrolled in the Women’s Health Initiative CaD trial (n = 36,282) were randomized to 1,000 mg calcium carbonate plus 400 IU of vitamin D3 daily or to placebo. Incident RA cases were identified via self-report and validated rheumatic medication use. Cox proportional hazards models were used to compare RA incidence in the treatment versus placebo groups. The analysis included 32,435 women without the history of RA, of which 163 incident RA cases were identified over an average of 5.1 years. No significant differences in demographics, total personal vitamin D intake [P = 0.36], or solar irradiance [P = 0.68] were seen between the groups. In intention-to-treat analyses, no differences were observed in RA incidence [HR 1.04, 95% CI 0.76, 1.41]. No significant modifying effects were seen for stratum of age, solar irradiance, or total vitamin D intake, overall or when adjusted for adherence. Significant effect modifications were seen between CaD and total vitamin D intake and CaD and solar irradiance that suggest increased RA incidence with high vitamin D exposure. CaD supplementation did not demonstrate a significant effect on RA incidence in postmenopausal women. Modifying effects between CaD and both solar irradiance and dietary vitamin D intake are suggestive that multiple high vitamin D exposures may increase RA incidence. Further research is needed to fully explore the benefits and possible adverse effects of vitamin D supplementation on RA.

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Acknowledgments

We thank Rachel Schaperow, MedStar Health Research Institute, for editing the manuscript.

Conflict of interest

Dr. B. V. Howard has served on the advisory boards of Merck/Schering Plough and has received research support in the form of drug donations from Merck/Schering Plough. The other authors have nothing to declare.

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Authors and Affiliations

  1. Washington Hospital Center, 110 Irving Street, Washington, DC, 20010, USA

    Marius Racovan, Brian Walitt & Christopher E. Collins

  2. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Mary Pettinger

  3. National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

    Christine G. Parks

  4. University of Alabama at Birmingham, Birmingham, AL, USA

    James M. Shikany

  5. University at Buffalo, SUNY, Buffalo, NY, USA

    Jean Wactawski-Wende

  6. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    JoAnn E. Manson

  7. University of Pittsburgh, Pittsburgh, PA, USA

    Larry Moreland

  8. University of Arizona, Tucson, AZ, USA

    Nicole Wright

  9. Ohio State University, Columbus, OH, USA

    Rebecca Jackson

  10. MedStar Health Research Institute, Hyattsville, MD, USA

    Barbara V. Howard

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  1. Marius Racovan
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  2. Brian Walitt
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  3. Christopher E. Collins
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  4. Mary Pettinger
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  5. Christine G. Parks
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  7. Jean Wactawski-Wende
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  9. Larry Moreland
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  10. Nicole Wright
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  12. Barbara V. Howard
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Correspondence to Brian Walitt.

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Racovan, M., Walitt, B., Collins, C.E. et al. Calcium and vitamin D supplementation and incident rheumatoid arthritis: the Women’s Health Initiative Calcium plus Vitamin D trial. Rheumatol Int 32, 3823–3830 (2012). https://doi.org/10.1007/s00296-011-2268-1

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  • DOI: https://doi.org/10.1007/s00296-011-2268-1

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