caa a22 4500 605520712 CHVBK 20210128100736.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00223-015-0017-2 doi (NATIONALLICENCE)springer-10.1007/s00223-015-0017-2 Attenuation of Antiresorptive Action in Withdrawal of Minodronic Acid for Three Months After Treatment for Twelve Months in Ovariectomized Rats [Elektronische Daten] [Makoto Tanaka, Hiroshi Mori, Kazuhito Kawabata] The purpose of this study was to evaluate the effects of withdrawal of minodronic acid (MIN) for 3months after 12months of treatment in ovariectomized (OVX) rat. OVX rats were orally treated with MIN (6, 30, and 150µg/kg/day) for 12months and necropsied on the day after the last dosing or following 3months of withdrawal. Lumbar and femoral BMD were decreased in OVX controls. MIN dose-dependently increased BMD. Withdrawal eliminated the effect of MIN on BMD loss after treatment at 6µg/kg, but not after treatment at 30 and 150µg/kg. In MIN-treated rats, trabecular thinning occurred during withdrawal after treatment at 6µg/kg, but the trabecular microstructure was maintained at 30 and 150µg/kg. In a mechanical test of the femoral diaphysis, stiffness of in OVX controls was decreased but ultimate load was similar to that in sham after withdrawal. MIN increased ultimate load and stiffness, but endosteal length decreased after withdrawal. Suppression of bone turnover by MIN based on bone turnover markers and histomorphometric indices was attenuated by withdrawal after treatment at 6 and 30µg/kg and partially at 150µg/kg. The MIN concentration in the humerus decreased during withdrawal, and half-life at 30µg/kg was shorter than that at 150µg/kg. These results show that the antiresorptive action of MIN was dose-dependently attenuated by 3-month withdrawal in a rat OVX model. An absence of BMD increase was only observed at a low dose but decreases in antiresorptive activity occurred over a wide dose range. Springer Science+Business Media New York, 2015 Minodronic acid nationallicence Osteoporosis nationallicence Bisphosphonate nationallicence Withdrawal nationallicence Ovariectomized rats nationallicence Tanaka Makoto Research Promotion, Ono Pharmaceutical Co., Ltd., 3-1-1, Sakurai, Shimamoto-cho, 618-8585, Osaka, Japan aut Mori Hiroshi Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., Shimamoto-cho, 618-8585, Osaka, Japan aut Kawabata Kazuhito Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., Shimamoto-cho, 618-8585, Osaka, Japan aut Calcified Tissue International Springer US; http://www.springer-ny.com 97/4(2015-10-01), 402-411 0171-967X 97:4<402 2015 97 223 https://doi.org/10.1007/s00223-015-0017-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-0017-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tanaka Makoto Research Promotion, Ono Pharmaceutical Co., Ltd., 3-1-1, Sakurai, Shimamoto-cho, 618-8585, Osaka, Japan aut NATIONALLICENCE 700 1- Mori Hiroshi Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., Shimamoto-cho, 618-8585, Osaka, Japan aut NATIONALLICENCE 700 1- Kawabata Kazuhito Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., Shimamoto-cho, 618-8585, Osaka, Japan aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 97/4(2015-10-01), 402-411 0171-967X 97:4<402 2015 97 223