title: Effects of vitamin K2 (menatetrenone) and alendronate on bone mineral density and bone strength in rats fed a low-magnesium diet.
abstract: In this study, we examined changes in bone parameters and bone strength in rats fed low-Mg diets (experiment 1) and the effects of vitamin K2 (MK-4, experiment 3) and alendronate (ALN, experiment 2) in this model. In experiment 1, 5-week-old male Wistar rats were fed three low-Mg diets (Mg 9, 6, 3 mg/100 g diet) for 4 weeks. Although the cortical bone mineral content (CtBMC) and cortical thickness (CtTh) of the femoral diaphysis in all low-Mg-diet groups were the same as or greater than those in the intact group (Mg: 90 mg/100 g diet), the maximum load and elastic modulus were significantly reduced in the 3-mg-Mg group. In experiment 2, 4-week-old Wistar rats were fed a 6-mg-Mg diet for 8 weeks, and the effect of ALN (2, 20, and 200 microg/kg twice a week) was evaluated. The administration of ALN at 200 microg/kg increased the cortical bone mineral content (CtBMC), CtTh, and maximum load, but had no effect on the elastic modulus, as compared with the low-Mg-control group. In experiment 3, the effect of MK-4 was evaluated under the same conditions as in experiment 2. The administration of MK-4 had no effect on CtBMC, CtTh, or bone components of the femoral diaphysis. However, MK-4 inhibited the decreases in maximum load and elastic modulus due to the low-Mg diet. Since there is no other experimental model in which there is a decrease in bone mechanical properties without a decrease in bone mineral content, the low-Mg diet model is considered to be an excellent model for examining bone quality. Our results from this model suggest that MK-4 and ALN affect bone mechanical properties by different mechanisms.
authors.affiliation: Pharmacological Evaluation Section, Department of Applied Drug Research, Eisai Co., Ltd., Bunkyo, Tokyo 112-8088, Japan. m-kobayashi@hhc.eisai.co.jp
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000032:analysis; D004548:Elasticity / Q000187:drug effects; D005269:Femur / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D006909:Hydroxyproline / Q000032:analysis; D008274:Magnesium / Q000032:analysis / Q000097:blood; D008275:Magnesium Deficiency / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D015675:Osteocalcin / Q000032:analysis / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D014556:Urine / Q000737:chemistry; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010281:Parathyroid Hormone; D015675:Osteocalcin; D024482:Vitamin K 2; C030814:menatetrenone; D000469:Alkaline Phosphatase; D002117:Calcitriol; D008274:Magnesium; D006909:Hydroxyproline; D002118:Calcium; D019386:Alendronate