title: Effects of combination treatment with alendronate and vitamin K(2) 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 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.
authors.affiliation: Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. yuisasa@doc.med.akita-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Naohisa
authors.initials: N
authors.lastname: Miyakoshi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kasukawa
authors.forename: Shigeto
authors.initials: S
authors.lastname: Maekawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Noguchi
authors.forename: Keji
authors.initials: K
authors.lastname: Kamo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D019386:Alendronate / Q000627:therapeutic use*; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D005260:Female; D005269:Femur / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000188:drug therapy; D010052:Ovariectomy; D024482:Vitamin K 2 / Q000627:therapeutic use*
chemical_list: D050071:Bone Density Conservation Agents; D024482:Vitamin K 2; D019386:Alendronate