Significant reduction in bone mineral density (BMD) occurs in
stroke patients on the hemiplegic and contralateral sides, correlating with the degree of
paralysis and
vitamin D and K deficiency due to
malnutrition, and increasing the risk of hip fracture. We evaluated the efficacy of
vitamin K2 (
menatetrenone:
menaquinone-4; MK-4) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients. In a random and prospective study, of 108 hemiplegic patients following
stroke, 54 received 45 mg
menatetrenone daily (MK-4 group, n = 54) for 12 months, and the remaining 54 (untreatment group) did not. Nine patients excluded from the study. The BMD in the second metacarpals and serum indices of bone metabolism were determined. BMD on the hemiplegic side increased by 4.3% in the MK-4 group and decreased by 4.7% in the untreated group (p < 0.0001), while BMD on the intact side decreased by 0.9% in the MK-4 group and by 2.7% in the untreated group (p < 0.0001). At baseline, patients of both groups showed
vitamin D and K1 deficiencies, high serum levels of ionized
calcium,
pyridinoline cross-linked carboxyterminal telopeptide of
type I collagen (ICTP), and low levels of parathyroid
hormones (PTH) and bone Gla
proteins (BGP), indicating that immobilization-induced
hypercalcemia inhibits renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[
OH]2D) and compensatory PTH secretion. Both
vitamins K1 and K2 increased by 97.6% and 666.9%, respectively, in the MK-4 group. Correspondingly, a significant increase in BGP and decreases in both ICTP and
calcium were observed in the MK-4 group, in association with a simultaneous increase in both PTH and 1, 25-[
OH]2D. One patient in the untreated group suffered from a hip fracture, compared with none in the MK-4 group. The treatment with MK-4 can increase the BMD of disused and
vitamin D- and K-deficient hemiplegic bone by increasing the
vitamin K concentration, and it also can decrease
calcium levels through inhibition of
bone resorption, resulting in an increase in 1, 25-[
OH]2D concentration.