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 Mar 25;41(3):211-21. doi: 10.1016/s0378-5122(01)00275-4.


Objectives: To investigate the therapeutic effect of combined use of vitamin K(2) and D(3) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis.

Subjects and methods: We enrolled 172 women with vertebral bone mineral density <0.98 g/cm(2) (osteopenia and osteoporosis) as measured by dual-energy X-ray absorptiometry. In this study, we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996. Subjects were randomized into four groups (each having 43 subjects in vitamin K(2) therapy group, vitamin D(3) therapy group, vitamin K(2) and D(3) combined therapy group, or a control group receiving dietary therapy alone) and treated with respective agents for 2 years, with bone mineral density was measured prior to therapy and after 6, 12, 18, and 24 months of treatment. The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide (P1CP), serum intact osteocalcin, and urinary pyridinoline. Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time (APTT) and analysis of concentrations of antithrombin III (AT III), fibrinogen, and plasminogen.

Results: Combined therapy with vitamin K(2) and D(3) for 24 months markedly increased bone mineral density (4.92 +/- 7.89%), while vitamin K(2) alone increased it only 0.135 +/- 5.44%. The bone markers measured, revealed stimulation of both bone formation and resorption activity. We observed an increase in coagulation and fibrinolytic activity that was within the normal range, suggesting that balance was maintained in the fibrinolysis-coagulation system.

Conclusions: Continuous combination therapy with vitamin K(2) and D(3) may be useful for increasing vertebral bone mass in postmenopausal women. Furthermore, the increase in coagulation function observed during this therapy was within the physiological range, and no adverse reactions were observed.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Amino Acids / urine
  • Antithrombin III / metabolism
  • Blood Coagulation Tests
  • Bone Density / drug effects*
  • Cholecalciferol / administration & dosage*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fibrinogen / metabolism
  • Humans
  • Middle Aged
  • Osteocalcin / blood
  • Osteoporosis, Postmenopausal / drug therapy*
  • Peptide Fragments / blood
  • Plasminogen / metabolism
  • Procollagen / blood
  • Treatment Outcome
  • Vitamin K 2 / administration & dosage*


  • Amino Acids
  • Peptide Fragments
  • Procollagen
  • procollagen type I carboxy terminal peptide
  • Osteocalcin
  • Vitamin K 2
  • Cholecalciferol
  • pyridinoline
  • Antithrombin III
  • Fibrinogen
  • Plasminogen