| [ Summary ] |
The drug alendronate decreases the risk of femoral neck fractures by suppressing bone turnover, and also decreases serum total osteocalcin levels. Low serum carboxylated osteocalcin levels or high undercarboxylated osteocalcin levels could be risk factors for femoral neck fracture. Vitamin K mediates carboxylation of osteocalcin, but the effect of alendronate therapy with or without vitamin K2 supplementation remains unknown. Forty eight postmenopausal women were enrolled in a one year prospective randomized trial and assigned to alendronate monotherapy (5 mg/day) (group A, n=26) or vitamin K2 (45 mg/day) plus alendronate (5 mg/day) (group AK, n=22). Bone mineral density was measured by dual‒energy X‒ray absorptiometry at 0 and 12 months. Bone turnover parameters were measured at 0, 3, and 12 months. Four patients discontinued alendronate therapy, and we analyzed the remaining 44 patients (23 in group A and 21 in group AK) who completed one year of treatment. Alendronate decreased undercarboxylated osteocalcin, while carboxylated osteocalcin was not affected. Addition of vitamin K2 enhanced the decrease of undercarboxylated osteocalcin levels and led to a greater increase in femoral neck bone mineral density. Alendronate monotherapy does not decrease carboxylation of osteocalcin. A combination of vitamin K2 and alendronate provides further benefits to both osteocalcin carboxylation and BMD of femoral necks in postmenopausal women with osteoporosis. A recent report revealed that serum levels of undercarboxylated osteocalcin in patients with incident fractures and who received bisphosphonate treatment was significantly higher than that in patients without incident fractures who received bisphosphonate treatment. Furthermore, another report elucidated that alendronate, alone or in combination with vitamin K2, provided significant improvement in BMD, but that the combination treatment was more effective than alendronate alone in terms of improving bone strength in ovariectomized mice. |