title: Effect of intermittent and daily regimens of minodronic Acid on bone metabolism in an ovariectomized rat model of osteoporosis.
abstract: The goal of the study was to compare the effects of minodronic acid on bone mineral density (BMD) and bone turnover in a rat ovariectomized (OVX) osteoporosis model, using two intermittent treatment regimens (weekly and 4 continuous days every 4 weeks) and a daily regimen. Female F344 rats (age 14 weeks) underwent ovariectomy or a sham operation. Minodronic acid was orally administered at 0.042, 0.21, and 1.05 mg/kg in the intermittent regimens, and at 0.03 and 0.15 mg/kg in the daily regimen for 12 weeks from the day after surgery. Minodronic acid dose-dependently ameliorated the decreases in areal BMD of the lumbar vertebrae and femur, and volumetric BMD of total and trabecular bone in the distal femur. Minodronic acid also suppressed the increase in urinary deoxypyridinoline levels and reduced serum osteocalcin levels. In bone histomorphometry, all three minodronic acid regimens suppressed OVX-induced increases in bone turnover at the tissue level and ameliorated all structural indices, except that an effect on trabecular thickness only occurred with daily treatment. In conclusion, minodronic acid administered weekly or for 4 continuous days every 4 weeks suppressed increased bone resorption and BMD to a similar extent to that of a similar total dose given daily in a rat OVX model.
authors.affiliation: Research Promotion, Ono Pharmaceutical Co., Ltd., 3-1-1, Sakurai, Shimamoto-cho, Mishima-gun, Osaka, 618-8585, Japan, mak.tanaka@ono.co.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kayasuga
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ochi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawada
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Kawabata
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage*; D010024:Osteoporosis / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; C087958:YM 529