Effect of Intermittent and Daily Regimens of Minodronic Acid on Bone Metabolism in an Ovariectomized Rat Model of Osteoporosis
Effect of Intermittent and Daily Regimens of Minodronic Acid on Bone Metabolism in an Ovariectomized Rat Model of Osteoporosis
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米诺膦酸间歇和每日治疗方案对去势大鼠骨质疏松模型骨代谢的影响
DOI：
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发表时间：
2014
影响因子：
4.2
通讯作者：
K. Kawabata
中科院分区：
文献类型：
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作者：
Makoto Tanaka;H. Mori;Ryoji Kayasuga;Y. Ochi;H. Yamada;Naoki Kawada;K. Kawabata
本研究的目的是比较米诺膦酸对大鼠卵巢切除（OVX）骨质疏松症模型中骨矿物质密度（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周一次连续4天）和每日一次。雌性F344大鼠（14周龄）进行卵巢切除术或假手术。从手术后第一天起，间歇方案中口服0.042、0.21和1.05 mg/kg米诺膦酸，每日方案中口服0.03和0.15 mg/kg米诺膦酸，持续12周。米诺膦酸剂量依赖性地改善腰椎和股骨的面积BMD以及股骨远端总骨和松质骨的体积BMD的降低。米诺膦酸还抑制尿脱氧吡啶啉水平的增加，并降低血清骨钙素水平。在骨组织形态计量学中，所有三种米诺膦酸方案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，但对骨小梁厚度的影响仅发生在每日治疗中。总之，每周一次或每4周连续4天给予米诺膦酸抑制骨吸收和BMD增加的程度与大鼠OVX模型中每天给予类似总剂量的程度相似。
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.