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The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial

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Abstract

Summary

We conducted a randomized placebo-controlled double-blinded clinical trial of MK-7 or placebo daily for 3 years in postmenopausal women with osteopenia. BMD decreased at all sites without differences between the MK-7 and placebo-treated women. Changes in bone turnover markers and microstructure were similar between the two groups.

Introduction

Vitamin K is a cofactor in the carboxylation of osteocalcin (OC) and carboxylated OC promotes mineralization of bone. Clinical studies suggest that vitamin K2 prevents bone loss. The aim of the study was to investigate the effect of vitamin K2 as an add-on to calcium and vitamin D supplementation on osteocalcin, bone mass, and microarchitecture in postmenopausal women.

Methods

We conducted a randomized placebo-controlled double-blinded clinical trial, including 142 postmenopausal women with osteopenia who received vitamin K2 (375 μg MK-7) or placebo daily for 3 years. Both groups received vitamin D3 (38 μg/day) and calcium (800 mg/day). We measured bone turnover markers in serum and bone mineral density and microarchitecture by DXA and HRpQCT.

Results

Undercarboxylated osteocalcin decreased in the MK-7-group (− 65.2 ± 23.5%) (mean ± SD) compared with the placebo group (− 0.03 ± 38.5%), p < 0.01 after 1 year. After 3 years, aBMD decreased at all sites without differences between the MK-7 and placebo-treated women (p > 0.09). aBMD decreased at the total hip by 1.5 ± 2.5% and 2.4 ± 2.7% in the MK-7 and the placebo groups, respectively, at the femoral neck by 1.5 ± 3.5% and 1.0 ± 5.0% in the MK-7 and the placebo groups, respectively, and at the lumbar spine by 1.8 ± 3.9% and 1.1 ± 3.1% in the MK-7 and the placebo groups, respectively. Changes in bone turnover markers were also similar between the two groups.We have previously reported improved microarchitecture with MK-7 after 1 year. However, changes in microstructure over 3 years were similar between the two groups, as assessed by both HRpQCT and DXA trabecular bone score.

Conclusion

Treatment with MK-7 375 μg daily as an add-on to calcium and vitamin D increased carboxylation of osteocalcin. However, treatment of postmenopausal women with osteopenia for 3 years did not affect biochemical markers of bone turnover, bone mineral density, or bone microarchitecture.

Trial registration

The study was registered at Clinicaltrial.gov:NCT01922804.

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Acknowledgments

We would like to thank dr. D. Rizopoulos for the advice on statistical analyses of the trabecular bone score data.

Funding

This work received financial supported from Orkla Health, which also supplied vitamin MK-7, placebo tablets, calcium, and vitamin D. The study was supported by Aase and Ejnar Danielsens Foundation, the Danish Osteoporosis Society, the Family Hede Nielsens Foundation, the Department of Endocrinology at Aarhus University Hospital Research Foundation, and the Central Denmark Region Research Foundation.

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Authors and Affiliations

  1. Aarhus University Hospital, Palle Juul-Jensen Boulevard 99, 8200, Aarhus N, Denmark

    S.H. Rønn, T. Harsløf, L. Oei, S.B. Pedersen & B.L. Langdahl

  2. Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands

    L. Oei

Authors
  1. S.H. Rønn
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  2. T. Harsløf
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  3. L. Oei
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  4. S.B. Pedersen
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  5. B.L. Langdahl
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Corresponding author

Correspondence to B.L. Langdahl.

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Conflict of interest

SHR, LO and SBP have nothing to disclose. TH has received honoraria for lectures from Amgen and Eli Lilly. BL has received research funding from Novo Nordisk and Amgen and has received honoraria for lectures and advisory boards from Amgen, UCB, Eli Lilly, Gilead, and Gedeon-Richter.

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Rønn, S., Harsløf, T., Oei, L. et al. The effect of vitamin MK-7 on bone mineral density and microarchitecture in postmenopausal women with osteopenia, a 3-year randomized, placebo-controlled clinical trial. Osteoporos Int 32, 185–191 (2021). https://doi.org/10.1007/s00198-020-05638-z

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  • DOI: https://doi.org/10.1007/s00198-020-05638-z

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