Effect of high-dose vitamin D supplementation on peripheral arterial calcification: secondary analysis of a randomized controlled trial

Abstract

Summary

Although high-dose vitamin D supplementation is common, effects on arterial calcification remain unexplored. Tibial artery calcification was identified and quantified over 3 years in participants randomized to 400, 4000, or 10,000 IU vitamin D3 daily. High-dose vitamin D supplementation did not affect the development or progression of arterial calcification.

Introduction

To determine whether vitamin D supplementation has a dose-dependent effect on development and progression of arterial calcification.

Methods

This was a secondary analysis of the Calgary Vitamin D Study, a 3-year, double-blind, randomized controlled trial conducted at a single-center in Calgary, Canada. Participants were community-dwelling adults aged 55–70 years with serum 25-hydroxyvitamin D 30–125 nmol/L. Participants were randomized 1:1:1 to receive vitamin D3 400, 4000, or 10,000 IU/day for 3 years. Tibial artery calcification was identified and quantified (in milligrams of hydroxyapatite, mgHA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6, 12, 24, and 36 months. Changes in calcification over time and treatment group interaction were evaluated using a constrained linear mixed effects model.

Results

Of 311 randomized participants, 302 (400: 105, 4000: 96, 10,000: 101) were eligible for analysis of arterial calcification (54% male, mean (SD) age 62 (4) years, mean (SD) 25-hydroxyvitamin D 78.9 (19.9) nmol/L). At baseline, 85 (28%) had tibial artery calcification, and mean (95% CI) calcification quantity was 2.8 mgHA (95% CI 1.7–3.9). In these 85 participants, calcification quantity increased linearly by 0.020 mgHA/month (95% CI 0.012–0.029) throughout the study, with no evidence of a treatment-group effect (p = 0.645 for interaction). No participants developed new arterial calcifications during the study.

Conclusions

In this population of community-dwelling adults who were vitamin D replete at baseline, supplementation with vitamin D 400, 4000, or 10,000 IU/day did not have differential effects on the development or progression of arterial calcification over 3 years.

Trial registration

clinicaltrials.gov (NCT01900860)

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Data availability

The authors commit to making relevant anonymized patient-level data, a study protocol, and a statistical analysis plan available to researchers who provide a methodologically sound proposal. Data will be available from 6 months following publication until 5 years following publication. To gain access, data requestors will need to sign a data access agreement.

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Acknowledgments

The authors wish to thank Duncan Boyd for his assistance with quantification of arterial calcifications, and Shawn Davison for his contribution to the literature review. Sharon Gaudet and Michelle Kan coordinated the study. Radiology technologists Anne Cooke, Stephanie Kwong, and Taryn Grant were instrumental in the acquisition of the HR-pQCT scans. The authors would also like to acknowledge Duncan Raymond for his work in organizing and cleaning the HR-pQCT scans. In addition, we extend our gratitude to the men and women of Alberta who participated in this trial.

Funding

This study was funded by Pure North S’Energy Foundation in response to an investigator-initiated research proposal.

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Correspondence to E. O. Billington.

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LAB, RP, MSR, and DAH have nothing to declare. EOB has previously received honoraria from Amgen and Eli Lilly, and a research grant from Amgen. SKB has received honorariums from Amgen and Servier, and is co-owner of Numerics88 Solutions Inc.

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Billington, E.O., Burt, L.A., Plett, R. et al. Effect of high-dose vitamin D supplementation on peripheral arterial calcification: secondary analysis of a randomized controlled trial. Osteoporos Int 31, 2141–2150 (2020). https://doi.org/10.1007/s00198-020-05500-2

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Keywords

  • HR-pQCT
  • Randomized controlled trial
  • Vascular calcification
  • Vitamin D