Vitamin K Supplementation Modulates Bone Metabolism and Ultra-Structure of Ovariectomized Mice

Cell Physiol Biochem. 2018;51(1):356-374. doi: 10.1159/000495234. Epub 2018 Nov 19.


Background/aims: Osteoporosis is a bone metabolic disease that affects mostly post-menopausal women. There has been shown that vitamin K (VK) supplementation during menopause may decrease bone loss as well as risk of bone breaking. Aiming to clarify the beneficial role of VK in bone metabolism during menopause, we investigated mineral metabolism and bone ultrastructure of ovariectomized (OVX) mice.

Methods: To determine the effects chronic use of VK in bone structure and mineral metabolism in OVX mice, we used several methods, such as DXA, µCTScan, and SEM as well as biomolecular techniques, such as ELISA and qRT-PCR. In addition, complete analysis of serum hormonal and other molecules associated to bone and lipid metabolism were evaluated overview the effects of VK in menopause murine model.

Results: VK treatment significantly affects Pi metabolism independently of OVX, changing Pi plasma, urinary output, balance, and Pi bone mass. Interestingly, VK also increased VLDL in mice independently of castration. In addition, VK increased compact bone mass in OVX mice when we evaluated it by DXA, histomorphometry, µCTScanning. VK increased bone formation markers, osteocalcin, HYP- osteocalcin, and AP whereas it decreased bone resorption markers, such as urinary DPD/creatinine ratio and plasmatic TRAP. Surprisingly, SEM images revealed that VK treatment led to amelioration of microfractures observed in OVX untreated controls. In addition, SHAM operated VK treated mice exhibited higher number of migrating osteoblasts and in situ secretion of AP. OVX led to decreased to in situ secretion of AP that was restored by VK treatment. Moreover, VK treatment increased mRNA expression of bone Calbindin 28KDa independently of OVX.

Conclusion: VK treatment in OVX mice exhibited beneficial effects on bone ultrastructure, mostly by altering osteoblastic function and secretion of organic bone matrix. Therefore, VK could be useful to treat osteopenic/osteoporotic patients.

Keywords: Bone Microarchitecture; Bone Mineral Density; Mineral Metabolism; Ovariectomized; Vitamin K.

MeSH terms

  • Alkaline Phosphatase / blood
  • Animals
  • Bone Density / drug effects*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism*
  • Bone and Bones / ultrastructure
  • Calbindins / genetics
  • Calbindins / metabolism
  • Creatinine / urine
  • Dietary Supplements
  • Disease Models, Animal
  • Female
  • Lipid Metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Scanning
  • Osteocalcin / blood
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • Ovariectomy
  • Parathyroid Hormone / blood
  • Spine / diagnostic imaging
  • Vitamin K / pharmacology*
  • X-Ray Microtomography


  • Calbindins
  • Parathyroid Hormone
  • Osteocalcin
  • Vitamin K
  • Creatinine
  • Alkaline Phosphatase