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Effect of vitamin D3 vs. calcifediol on VDR concentration and fiber size in skeletal muscle

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Abstract

Introduction

This study sought to examine the effect of vitamin D3 (VD3) 3200 IU/d, calcifediol (HyD) 20mcg/d, or placebo on intramyonuclear vitamin D receptor (VDR) concentration, muscle fiber cross-sectional area (FCSA), and muscle satellite cell activation.

Materials and methods

It was conducted on a subset of the VD3 (n = 12), HyD (n = 11), and placebo (n = 13) groups who participated in the 6-month randomized controlled HyD Osteopenia Study in postmenopausal women. Baseline and 6-month vastus lateralis muscle cross sections were probed for VDR, fiber type I and II, and PAX7 (satellite cell marker) using immunofluorescence.

Results

Baseline mean ± SD age was 61 ± 4 years and serum 25-hydroxyvitamin D (25OHD) level was 55.1 ± 22.8 nmol/L. Baseline characteristics did not differ significantly by group. Six-month mean ± SD 25OHD levels were 138.7 ± 22.2 nmol/L (VD3), 206.8 ± 68.8 nmol/L (HyD), and 82.7 ± 36.1 nmol/L (placebo), ANOVA P < 0.001. There were no significant group differences in 6-month change in VDR concentration (ANOVA P = 0.227). Mean ± SD percent 6-month changes in type I FCSA were 20.5 ± 32.7% (VD3), − 6.6 ± 20.4% (HyD), and − 0.3 ± 14.0% (placebo, ANOVA P = 0.022). Type II FCSA or PAX7 concentration did not change significantly by group (all P > 0.358).

Conclusion

This study demonstrated no significant change in intramyonuclear VDR in response to either form of vitamin D vs. placebo. Type I FCSA significantly increased with VD3, but not with HyD at 6 months. As type I fibers are more fatigue resistant than type II, enlargement in type I suggests potential for improved muscle endurance. Although HyD resulted in the highest 25OHD levels, no skeletal muscle benefits were noted at these high levels.

Clinical trial

NCT02527668.

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Acknowledgements

We thank Rahul Sangar for technical assistance with the skeletal muscle biopsy processing and immunofluorescent staining. We also thank Jonathan Pun for technical assistance with the VDR and PAX7 analyses. This research was supported by the DSM Nutritional Products Ltd. DSM did not contribute to the design of study, interpretation of the muscle tissue data, or writing of the manuscript. This material is also based upon work supported by the U.S. Department of Agriculture, Agricultural Research Service, under agreement No. 58-1950-7-707. Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Dept of Agriculture.

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Authors and Affiliations

  1. Division of EndocrinologyDiabetes and Metabolism, Tufts Medical Center, Boston, MA, 02111, USA

    Lisa Ceglia

  2. Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA

    Lisa Ceglia, Donato A. Rivas, Grace B. Fielding & Bess Dawson-Hughes

  3. Centre on Aging and Mobility, University of Zurich, Zurich, Switzerland

    Mathias Schlögl, Andreas Egli & Heike A. Bischoff-Ferrari

  4. Department of Aging Medicine, University Hospital Zurich and City Hospital Zurich, Zurich, Switzerland

    Heike A. Bischoff-Ferrari

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  1. Lisa Ceglia
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Contributions

LC, DAR, HB-F, and BD-H designed the research; LC, DAR, MS, GBF, and AE conducted the research; LC, DAR, and GBF analyzed muscle samples or performed statistical analysis; all authors contributed to the writing of the manuscript; LC had primary responsibility for the final content. All authors have read and approved the final manuscript.

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Correspondence to Lisa Ceglia.

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Conflict of interest

DAR, MS, GBF, and AE—none; LC, HB-F, and BDH – received investigator-initiated funding from DSM Nutritional Products. HB-F received speaker/travel honoraria from OM Pharma, Vifor, Wild, and EULAR guideline meeting, and served on the boards of Harvard Minding our Future Healthy Ageing, ProSenectute, and Swiss Association against Osteoporosis.

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Ceglia, L., Rivas, D.A., Schlögl, M. et al. Effect of vitamin D3 vs. calcifediol on VDR concentration and fiber size in skeletal muscle. J Bone Miner Metab 41, 41–51 (2023). https://doi.org/10.1007/s00774-022-01374-y

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