Vitamin K₂ Therapy for Postmenopausal Osteoporosis

Overview

Journal Nutrients

Date 2014 May 21

PMID 24841104

Citations 39

Authors

Jun Iwamoto

Affiliations

Soon will be listed here.

Abstract

Vitamin K may play an important role in the prevention of fractures in postmenopausal women with osteoporosis. Menatetrenone is the brand name of a synthetic vitamin K2 that is chemically identical to menaquinone-4. The present review study aimed to clarify the effect of menatetrenone on the skeleton in postmenopausal women with osteoporosis, by reviewing the results of randomized controlled trials (RCTs) in the literature. RCTs that investigated the effect of menatetrenone on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and fracture incidence in postmenopausal women with osteoporosis, were identified by a PubMed search for literature published in English. Eight studies met the criteria for RCTs. Small RCTs showed that menatetrenone monotherapy decreased serum undercarboxylated osteocalcin (ucOC) concentrations, modestly increased lumbar spine BMD, and reduced the incidence of fractures (mainly vertebral fracture), and that combined alendronate and menatetrenone therapy enhanced the decrease in serum ucOC concentrations and further increased femoral neck BMD. This review of the literature revealed positive evidence for the effects of menatetrenone monotherapy on fracture incidence in postmenopausal women with osteoporosis. Further studies are required to clarify the efficacy of menatetrenone in combination with bisphosphonates against fractures in postmenopausal women with osteoporosis.

Citing Articles

Effects of vitamin K supplementation on bone mineral density at different sites and bone metabolism in the middle-aged and elderly population.

Xie C, Gong J, Zheng C, Zhang J, Gao J, Tian C Bone Joint Res. 2024; 13(12):750-763.

PMID: 39657786 PMC: 11631259. DOI: 10.1302/2046-3758.1312.BJR-2024-0053.R1.

Mechanistic Insights and Therapeutic Strategies in Osteoporosis: A Comprehensive Review.

Elahmer N, Wong S, Mohamed N, Alias E, Chin K, Muhammad N Biomedicines. 2024; 12(8).

PMID: 39200100 PMC: 11351389. DOI: 10.3390/biomedicines12081635.

Osteoporosis treatment: current drugs and future developments.

Chen Y, Jia L, Han T, Zhao Z, Yang J, Xiao J Front Pharmacol. 2024; 15:1456796.

PMID: 39188952 PMC: 11345277. DOI: 10.3389/fphar.2024.1456796.

Vitamin K2 sensitizes the efficacy of venetoclax in acute myeloid leukemia by targeting the NOXA-MCL-1 pathway.

Tauchi T, Moriya S, Okabe S, Kazama H, Miyazawa K, Takano N PLoS One. 2024; 19(7):e0307662.

PMID: 39052583 PMC: 11271855. DOI: 10.1371/journal.pone.0307662.

The Effect of Vitamin K2 Supplementation on PIVKA-II Levels in Patients with Severe Motor and Intellectual Disabilities Undergoing Long-Term Tube Feeding.

Ohmori H, Kato A, Shirai Y, Fukano R, Nagae A, Yamasaki M Nutrients. 2023; 15(21).

PMID: 37960177 PMC: 10647752. DOI: 10.3390/nu15214525.

References

Purwosunu Y, Muharram , Rachman I, Reksoprodjo S, Sekizawa A . Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia. J Obstet Gynaecol Res. 2006; 32(2):230-4. DOI: 10.1111/j.1447-0756.2006.00386.x. View

. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994; 843:1-129. View

Iwamoto J, Sato Y, Takeda T, Matsumoto H . High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Nutr Res. 2009; 29(4):221-8. DOI: 10.1016/j.nutres.2009.03.012. View

Cheung A, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J . Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008; 5(10):e196. PMC: 2566998. DOI: 10.1371/journal.pmed.0050196. View

Shiraki M, Yamazaki Y, Shiraki Y, Hosoi T, Tsugawa N, Okano T . High level of serum undercarboxylated osteocalcin in patients with incident fractures during bisphosphonate treatment. J Bone Miner Metab. 2010; 28(5):578-84. DOI: 10.1007/s00774-010-0167-2. View

Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Nakamura T . Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Miner Metab. 2008; 27(1):66-75. DOI: 10.1007/s00774-008-0008-8. View

Shiraki M, Itabashi A . Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study. J Bone Miner Metab. 2009; 27(3):333-40. DOI: 10.1007/s00774-008-0034-6. View

Vermeer C, Jie K, Knapen M . Role of vitamin K in bone metabolism. Annu Rev Nutr. 1995; 15:1-22. DOI: 10.1146/annurev.nu.15.070195.000245. View

Iwamoto J, Takeda T, Ichimura S . Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J Orthop Sci. 2001; 5(6):546-51. DOI: 10.1007/s007760070003. View

10.

Iwamoto J, Takeda T, Ichimura S . Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate. J Orthop Sci. 2002; 6(6):487-92. DOI: 10.1007/s007760100002. View

11.

Ishida Y, Kawai S . RETRACTED: Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study. Am J Med. 2004; 117(8):549-55. DOI: 10.1016/j.amjmed.2004.05.019. View

12.

Hauschka P, Lian J, Cole D, Gundberg C . Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev. 1989; 69(3):990-1047. DOI: 10.1152/physrev.1989.69.3.990. View

13.

Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C . Increased bone formation in osteocalcin-deficient mice. Nature. 1996; 382(6590):448-52. DOI: 10.1038/382448a0. View

14.

Hirao M, Hashimoto J, Ando W, Ono T, Yoshikawa H . Response of serum carboxylated and undercarboxylated osteocalcin to alendronate monotherapy and combined therapy with vitamin K2 in postmenopausal women. J Bone Miner Metab. 2008; 26(3):260-4. DOI: 10.1007/s00774-007-0823-3. View

15.

Orimo H, Nakamura T, Hosoi T, Iki M, Uenishi K, Endo N . Japanese 2011 guidelines for prevention and treatment of osteoporosis--executive summary. Arch Osteoporos. 2012; 7:3-20. PMC: 3517709. DOI: 10.1007/s11657-012-0109-9. View

16.

Nakagawa K, Hirota Y, Sawada N, Yuge N, Watanabe M, Uchino Y . Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature. 2010; 468(7320):117-21. DOI: 10.1038/nature09464. View

17.

Koshihara Y, Hoshi K . Vitamin K2 enhances osteocalcin accumulation in the extracellular matrix of human osteoblasts in vitro. J Bone Miner Res. 1997; 12(3):431-8. DOI: 10.1359/jbmr.1997.12.3.431. View

18.

Ushiroyama T, Ikeda A, Ueki M . Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas. 2002; 41(3):211-21. DOI: 10.1016/s0378-5122(01)00275-4. View

19.

Shiraki M, Shiraki Y, Aoki C, Miura M . Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000; 15(3):515-21. DOI: 10.1359/jbmr.2000.15.3.515. View

20.

Knapen M, Schurgers L, Vermeer C . Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007; 18(7):963-72. PMC: 1915640. DOI: 10.1007/s00198-007-0337-9. View