Tanaka Makoto, Mori Hiroshi, Kayasuga Ryoji, Ochi Yasuo, Yamada Hiroyuki, Kawada Naoki, Kawabata Kazuhito
Research Promotion, Ono Pharmaceutical Co., Ltd., 3-1-1, Sakurai, Shimamoto-cho, Mishima-gun, Osaka, 618-8585, Japan,
Calcif Tissue Int. 2014 Aug;95(2):166-73. doi: 10.1007/s00223-014-9876-1. Epub 2014 Jun 6.
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.
本研究的目的是在大鼠卵巢切除（OVX）骨质疏松模型中，比较米诺膦酸对骨密度（BMD）和骨转换的影响，采用两种间歇治疗方案（每周一次和每4周连续4天）和一种每日治疗方案。雌性F344大鼠（14周龄）接受卵巢切除术或假手术。从手术后第二天起，米诺膦酸以0.042、0.21和1.05mg/kg的剂量用于间歇治疗方案，以0.03和0.15mg/kg的剂量用于每日治疗方案，持续12周。米诺膦酸剂量依赖性地改善了腰椎和股骨的面积骨密度以及股骨远端全骨和小梁骨的体积骨密度的降低。米诺膦酸还抑制了尿脱氧吡啶啉水平的升高并降低了血清骨钙素水平。在骨组织形态计量学中，所有三种米诺膦酸治疗方案均在组织水平上抑制了OVX诱导的骨转换增加，并改善了所有结构指标，除了每日治疗仅对小梁厚度有影响。总之，在大鼠OVX模型中，每周给药或每4周连续4天给药的米诺膦酸抑制骨吸收增加和骨密度的程度与每日给予相似总剂量的情况相似。
