Significant reduction in bone mineral density (BMD) occurs in patients with
Parkinson's disease (PD), correlating with immobilization and with
vitamin D deficiency, and increasing the risk of hip fracture, especially in elderly women. As a
biological indicator of compromised
vitamin K status, an increased serum concentration of undercarboxylated
osteocalcin (Oc) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women. We evaluated treatment with
vitamin K(2) (
menatetrenone; MK-4) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD. In a random and prospective study of PD patients, 60 received 45 mg of MK-4 daily for 12 months, and the remaining 60 (untreated group) did not. At baseline, patients of both groups showed
vitamin D and K(1) deficiencies, high serum levels of ionized
calcium, and glutaminic residue (Glu) Oc, and low levels of
parathyroid hormone (PTH) and
1,25-dihydroxyvitamin D [
1,25-(OH)(2)D], indicating that immobilization-induced
hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion. BMD in the second metacarpals increased by 0.9% in the treated group and decreased by 4.3% in the untreated group (p < 0.0001).
Vitamin K(2) level increased by 259.8% in the treated group. Correspondingly, significant decreases in Glu Oc and
calcium were observed in the treated group, in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures (eight at the hip and two at other sites) in the untreated group, and one hip fracture occurred among treated patients (p = 0.0082; odds ratio = 11.5). The treatment with MK-4 can increase the BMD of
vitamin D- and K-deficient bone by increasing
vitamin K concentration, and it can also decrease
calcium levels through inhibition of
bone resorption, resulting in an increase in 1,25-(OH)(2)D concentration.