Journal
JOURNAL OF BONE AND MINERAL METABOLISM
Volume 28, Issue 4, Pages 403-409Publisher
SPRINGER TOKYO
DOI: 10.1007/s00774-009-0148-5
Keywords
Alendronate; Vitamin K-2; Bone mineral density; Bone strength; Ovariectomized mice
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Bisphosphonates increase bone mineral density (BMD) by suppressing remodeling space and elongating the duration of mineralization. Menatetrenone (vitamin K-2) reduces the incidence of fractures by improving bone quality through enhanced gamma-carboxylation of bone glutamic acid residues of osteocalcin in osteoporotic patients. This study investigated the effects of combination treatment with alendronate (ALN) and vitamin K-2 on BMD and bone strength in ovariectomized (OVX) mice. Thirty-three female mice, 16 weeks of age, were assigned to four groups: (1) OVX-control group; (2) oral vitamin K-2 group; (3) subcutaneous ALN group; and (4) ALN + vitamin K-2 group. The treatment was started 4 weeks after OVX and continued for 4 weeks. BMD, geometric parameters measured by peripheral quantitative computed tomography, and mechanical strength at the femoral metaphysis and mid-diaphysis were evaluated after an 8-week treatment period. ALN alone significantly increased total BMD (20%, P < 0.05) and trabecular BMD (25%, P < 0.05), but not the mechanical parameters of the femur, compared with the OVX-control group. Combination treatment with ALN and vitamin K-2 increased not only total BMD (15%, P < 0.05) and trabecular BMD (32%, P < 0.05) but also maximum load (33%, P < 0.05) and breaking energy (25%, P < 0.05) of compression test at the distal metaphysis, and maximum load (20%, P < 0.05) and breaking force (33%, P < 0.05) of three-point bending test at the mid-diaphysis compared with the OVX-control group. These results suggest that ALN, alone or in combination with vitamin K-2, showed significant improvement in BMD, but that the combination treatment was more effective than ALN alone for improving bone strength in OVX mice.
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