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Effects of combination treatment with alendronate and vitamin K2 on bone mineral density and strength in ovariectomized mice

Abstract

Bisphosphonates increase bone mineral density (BMD) by suppressing remodeling space and elongating the duration of mineralization. Menatetrenone (vitamin K2) reduces the incidence of fractures by improving bone quality through enhanced γ-carboxylation of bone glutamic acid residues of osteocalcin in osteoporotic patients. This study investigated the effects of combination treatment with alendronate (ALN) and vitamin K2 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 K2 group; (3) subcutaneous ALN group; and (4) ALN + vitamin K2 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 K2 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 K2, 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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Acknowledgments

We thank Kaoru Sakamoto for her technical assistance in this research.

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Correspondence to Hiroshi Sasaki.

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Sasaki, H., Miyakoshi, N., Kasukawa, Y. et al. Effects of combination treatment with alendronate and vitamin K2 on bone mineral density and strength in ovariectomized mice. J Bone Miner Metab 28, 403–409 (2010). https://doi.org/10.1007/s00774-009-0148-5

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  • DOI: https://doi.org/10.1007/s00774-009-0148-5

Keywords

  • Alendronate
  • Vitamin K2
  • Bone mineral density
  • Bone strength
  • Ovariectomized mice