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Bone Microstructure in Response to Vitamin D3 Supplementation: A Randomized Placebo-Controlled Trial


Vitamin D supplementation is often used in the prevention and treatment of osteoporosis, but the role of vitamin D has lately been questioned. We aimed to investigate the effect of 3 months of daily vitamin D3 supplementation (70 µg [2800 IU] vs. placebo) initiated in winter months on bone health. This study is a double-blinded placebo-controlled randomized trial. Bone health was assessed by bone turnover markers, DXA, HRpQCT, and QCT scans. The participants were 81 healthy postmenopausal women with low 25(OH)D (< 50 nmol/l) and high PTH levels (> 6.9 pmol/l) at screening. Vitamin D3 supplementation significantly increased levels of 25(OH)D and 1,25(OH)2D by 59 nmol/l and 19 pmol/l, respectively, whereas PTH was reduced by 0.7 pmol/l (all p < 0.0001). Compared with placebo, vitamin D3 did not affect bone turnover markers, aBMD by DXA or trabecular bone score. Vitamin D3 increased trabecular vBMD (QCT scans) in the trochanter region (0.4 vs. − 0.7 g/cm3) and the femoral neck (2.1 vs. − 1.8 g/cm3) pall < 0.05. HRpQCT scans of the distal tibia showed reduced trabecular number (− 0.03 vs. 0.05 mm−1) and increased trabecular thickness (0.001 vs. − 0.005 mm), as well as an improved estimated bone strength as assessed by failure load (0.1 vs. − 0.1 kN), and stiffness (2.3 vs. − 3.1 kN/mm pall ≤ 0.01). Changes in 25(OH)D correlated significantly with changes in trabecular thickness, stiffness, and failure load. Three months of vitamin D3 supplementation improved bone strength and trabecular thickness in tibia, vBMD in the trochanter and femoral neck, but did not affect aBMD.

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We acknowledge the funding from Aarhus University, The Augustinus Foundation, Toyota Foundation, A.P. Møller & wife Chastine MC-Kinney Møllers Foundation, and P. A. Messerschmidt & wife foundation. Orkla Health donated vitamin D and vitamin D placebo tablets free of charge, but had no influence on analyses and interpretation of data. Most importantly, we thank all participants for their extraordinary enthusiasm and cooperativeness. We acknowledge the Danish Health Data Authority, Orkla Health A/S, laboratory technicians, the hospital pharmacy and the Department of Radiology, Aarhus University Hospital.

Author information




LSB: study design, collection of data; analysis, drafting the manuscript, responsible for data integrity analysis. LLR: data collection, critical revision, and approval of the manuscript. LRo and TS: study design, critical revision, and approval of the manuscript. LRe: study design, analysis, and interpretation of data, as well as critical revision and approval of the manuscript.

Corresponding author

Correspondence to Lise Sofie Bislev.

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Conflict of interest

Lise Sofie Bislev, Lene Langagergaard Rødbro, Lars Rolighed, Tanja Sikjaer, and Lars Rejnmark declare that they have no conflict of interest and no competing financial interests.

Ethical Approval

We performed the study in accordance to the Helsinki II declaration considering biomedical research and obtained informed, written consent from all participants.

Human and Animal Rights

The study was approved by the Danish Data Protection Agency (1-16-02-492-14), the Regional Committee on Biomedical Research Ethics (1-10-72-326-14), the Danish Health Authority (2014-003645-10) and Danish Health Data Authority (FSEID-00001274). The local unit for Good Clinical Practice at Aarhus University Hospital monitored the study. identifier: #NCT02572960.

Informed Consent

All study participants gave their written informed consent.

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Bislev, L.S., Langagergaard Rødbro, L., Rolighed, L. et al. Bone Microstructure in Response to Vitamin D3 Supplementation: A Randomized Placebo-Controlled Trial. Calcif Tissue Int 104, 160–170 (2019).

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  • Vitamin D
  • PTH
  • BMD
  • Trabecular bone microarchitecture
  • Estimated bone strength