Long-term safety of the aminobisphosphonate alendronate in adult dogs. II. Histomorphometric analysis of the L5 vertebrae.
Long-term safety of the aminobisphosphonate alendronate in adult dogs. II. Histomorphometric analysis of the L5 vertebrae.
复制标题
氨基二膦酸阿仑膦酸盐对成年犬的长期安全性。
DOI：
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发表时间：
1996
影响因子：
3.5
通讯作者：
G. Rodan
中科院分区：
文献类型：
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作者：
R. Balena;A. Markatos;J. Seedor;Michael A. Gentile;C. Stark;C. Peter;G. Rodan
骨质疏松症是一个主要的健康问题。双膦酸盐是一种合成化合物，它优先被骨骼吸收，并抑制破骨细胞介导的骨吸收。阿仑膦酸钠（ALN）是一种氨基二磷酸盐，用于治疗以骨吸收增加为特征的疾病，包括骨质疏松症。本研究的目的是为了排除长期服用ALN对骨质量可能产生的不良影响。选用31只20 ~ 21月龄的小猎犬（雌雄各7 ~ 8只），分别以0.00、0.25、0.5、1.00 mg/kg/d的ALN给药157周，并用土霉素和钙黄素进行体内标记。采用静态和动态组织形态测量法对取自第五腰椎的未钙化骨切片进行评估。皮质或松质骨体积和结构指标不受治疗的影响。治疗对骨样厚度和矿化滞后时间无影响。在男性中，组织水平的骨转换以剂量依赖的方式被抑制。结果表明，长期给药ALN达到临床试验中治疗骨质疏松所用剂量的5倍，不会导致骨重塑或骨结构异常。
Osteoporosis is a major health problem. Bisphosphonates are synthetic compounds that are taken up preferentially by the skeleton and suppress osteoclast-mediated bone resorption. Alendronate (ALN) is an aminobisphosphonate used in the treatment of diseases characterized by increased bone resorption including osteoporosis. The purpose of this study was to rule out possible adverse effects of the chronic administration of ALN on the quality of bone. Thirty-one 20- to 21-month-old beagles (n = 7-8 per group, females and males) were treated p.o. for 157 weeks with ALN at 0.00, 0.25, 0.5 or 1.00 mg/kg/day and labeled in vivo with oxytetracycline and calcein. Undecalcified bone sections obtained from the fifth lumbar vertebra were evaluated by static and dynamic histomorphometry. Cortical or cancellous bone volume and indices of architecture were not affected by treatment. Osteoid thickness and mineralization lag time were not changed by treatment. Tissue level bone turnover was inhibited in a dose-dependent manner in males. The results indicate that long-term ALN administration at up to 5 times the dose used for treatment of osteoporosis in clinical trials causes no abnormalities in bone remodeling or bone structure.