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Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens

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Abstract

Summary

Rationale: Calcidiol can be employed to correct vitamin D deficiency. Main results: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. Significance: Calcidiol supplementation is effective and safe.

Introduction

The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis. Despite cholecalciferol (vitamin D3) is the most commonly used drug for vitamin D supplementation, the more hydrophilic compound calcidiol (25-hydroxyvitamin D3) can be employed at daily, weekly, and monthly regimens to reach in the short term the target levels of serum 25-hydroxyvitamin D [25(OH)D]. In the administration of different doses of calcidiol pharmacokinetic study (ADDI-D study), the efficacy and safety of daily and weekly dosages of calcidiol were tested.

Methods

A total of 87 Caucasian, community-dwelling, postmenopausal women, aged 55 years or older, with vitamin D inadequacy (serum 25(OH)D levels <30 ng/ml, with mean 25(OH)D below 20 ng/ml, namely 16.5 ± 7.5 ng/ml) were randomized to receive three different dosages of calcidiol: 20 μg/day, 40 μg/day, and 125 μg/week for 3 months. The attained level of serum 25(OH)D was selected as primary endpoint to assess efficacy, while other parameters of mineral metabolism, (serum calcium, parathyroid hormone, phosphate, FGF23, urinary calcium, and markers of bone turnover) were assessed as secondary endpoints to establish safety.

Results

In all the three groups, serum 25(OH)D values significantly and promptly rose and plateaued above the 30 ng/ml threshold remaining within safety interval after 14 days of treatment, with similar efficacy for the similar daily and weekly dose regimens. The different dosages were also equally effective in controlling secondary hyperparathyroidism. No significant changes in calcium and phosphate metabolism and in bone turnover markers were observed for any of the treatments, confirming the safety of this compound.

Conclusions

The results of this study demonstrate the short- and mid-term efficacy and safety on core parameters of mineral metabolism of different daily or weekly dosages of calcidiol when used to treat vitamin D inadequacy or deficiency in postmenopausal women. Further studies are needed to assess falls as primary outcome of calcidiol supplementation.

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Acknowledgments

This work was supported though a dedicated grant from Bruno Farmaceutici (to Maria Luisa Brandi and Salvatore Minisola). We are indebted to Guido Fedele for the statistical analyses of the data.

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Authors and Affiliations

  1. Department of Internal Medicine and Medical Disciplines, “Sapienza”, University of Rome, Rome, Italy

    S. Minisola, P. Biondi, C. Cipriani & J. Pepe

  2. Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy

    L. Cianferotti, C. Fossi, F. Franceschelli, F. Giusti, G. Leoncini & M. L. Brandi

  3. Department of Geriatrics and Aging Research, University Hospital and University of Zurich, Zürich, Switzerland

    H. A. Bischoff-Ferrari

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  1. S. Minisola
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Correspondence to M. L. Brandi.

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Conflict of interest

Luisella Cianferotti, Piergianni Biondi, Caterina Fossi, Francesco Franceschelli, Francesca Giusti, Gigliola Leoncini, and Jessica Pepe declare that they have no conflict of interest.

Salvatore Minisola served as speaker for Abiogen, Amgen, Bruno Farmaceutici, Diasorin, Eli Lilly, Italfarmaco, Fujii, and Merck Sharp & Dohme, Takeda. He served in advisory board of Amgen, Eli Lilly, and Merck Sharp & Dohme and received paid consultancy from Bruno Farmaceutici.

Heike A. Bischoff-Ferrari contributed as invited speaker and on advisory boards for Roche, Pfizer, Sanofi, DSM Nutritional Products, Nestlé, and WILD. She received investigator initiated and independent funding from DSM Nutritional Products, Roche Diagnostics, Pfizer, and Nestlé.

Maria Luisa Brandi has received consultancy fees and grant support from Alexion, Abiogen, Amgen, Eli Lilly, and Shire.

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Minisola, S., Cianferotti, L., Biondi, P. et al. Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens. Osteoporos Int 28, 3239–3249 (2017). https://doi.org/10.1007/s00198-017-4180-3

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