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Combination use of vitamin K2 further increases bone volume and ameliorates extremely low turnover bone induced by bisphosphonate therapy in tail-suspension rats
Authors:Yoshiko Iwasaki  Hideyuki Yamato  Hisashi Murayama  Masami Sato  Takeshi Takahashi  Ikuko Ezawa  Kiyoshi Kurokawa  Masafumi Fukagawa
Affiliation:(1)  Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan, JP;(2)  Biomedical Research Laboratories, Kureha Chemical Co. Ltd., Tokyo, Japan, JP;(3)  Division of Nephrology and Clinical Research Center, Tokyo Teishin Hospital, Tokyo, Japan, JP;(4)  Department of Food and Nutrition, School of Home Economics, Japan Women's University, Tokyo, Japan, JP;(5)  Division of Nephrology, Tokai University School of Medicine, Kanagawa, Japan, JP;(6)  Division of Nephrology and Dialysis Center, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan, JP
Abstract: Bisphosphonate is a potent inhibitor of bone resorption, which results in the increase of bone volume. However, bisphosphonate treatment may lead to extremely low bone turnover and abnormal bone microstructure. In this study, we examined whether the combination of bisphosphonate with vitamin K2 treatment may have beneficial effects on bone turnover and trabecular microstructure as well as on bone volume loss by using tail-suspension model rats. In these model rats, bone mineral density (BMD) decreased with histological evidence of enhanced bone resorption and suppressed bone formation. By bisphosphonate treatment, BMD was increased compared with that of tail-suspended rats. Osteoclast surface per bone surface (Oc.S/BS) and number of osteoclasts per bone perimeter (N.Oc/B.Pm) were reduced and mineral apposition rate (MAR) decreased, suggesting extreme suppression of bone turnover. However, trabecular structure examined by microfocus CT was apparently abnormal. By contrast, combination of bisphosphonate with vitamin K2 leads to further increase of bone volume. MAR and BFR as well as Oc.S/BS and N.Oc/B.Pm were increased compared with those of the bisphosphonate-treated group. However, abnormal structure of trabeculae in secondary spongiosa was not completely ameliorated. These data suggested that concomitant use of vitamin K2 with bisphosphonate excessively ameliorates too much suppression of bone turnover while more efficiently preventing bone volume loss. Received: January 30, 2002 / Accepted: November 6, 2002 RID="*" ID="*"  Present address: Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, Japan Acknowledgments. This work was supported in part by a Special Grant for Medical Research from Ministry of Post and Telecommunications, Japan (to M.F.), a grant in aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (#13671115 to M.F.), and by a grant from the Research Society for Metabolic Bone Disease (to M.F.). We are grateful to Miss Sachiko Suzuki for technical assistance. Offprint requests to: M. Fukagawa
Keywords:  vitamin K2  bisphosphonate  bone turnover  microgravity  tail-suspension rats
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