Kippo K, Hannuniemi R, Laurén L, Peng Z, Isaksson P, Virtamo T, Osterman T, Pasanen I, Sellman R, Väänänen H K
Leiras Oy, Biomedical Research Center, P.O. Box 415, 20101 Turku, Finland.
Calcif Tissue Int. 1997 Aug;61(2):151-7. doi: 10.1007/s002239900314.
The purpose of this study was to investigate the ability of clodronate to prevent ovariectomy (OVX)-induced osteopenia in aged rats. Fourteen-month-old female Sprague-Dawley rats (n = 166) were randomized into six groups. One group was sacrificed at the start of the study, four groups were ovariectomized, and one group was sham-operated (Sham). The OVX rats were given subcutaneously either vehicle (veh) or clodronate at doses of 3, 7, or 25 mg/kg once a week for 3 months, and the Sham rats were given the vehicle. At all dose levels clodronate inhibited trabecular bone loss in the distal femur and in the fourth lumbar vertebral body (L4), and decreased bone resorption as evidenced by urinary deoxypyridinoline excretion. The lowest dose of clodronate preserved serum osteocalcin and endosteal bone formation of secondary spongiosa in L4 at the level of the Sham/veh group. The OVX-induced increase in periosteal bone formation of femoral diaphysis was unaffected by two smaller doses of clodronate, but was decreased to the level of Sham rats after the highest dose. After 3 mg/kg clodronate, the percentage of femoral cortical bone area and the mean relative cortical thickness were higher compared with the OVX/veh group. There was a good positive correlation between the maximum load in three-point bending of the tibia and tibial ash weight. Normal lamellar pattern of newly formed cancellous and cortical bone was found after clodronate treatment. No signs of adverse accumulation of osteoid or any deleterious effect on mechanical strength of long bones and lumbar vertebrae were found.
本研究的目的是调查氯膦酸盐预防老年大鼠卵巢切除（OVX）诱导的骨质减少的能力。将14月龄雌性Sprague-Dawley大鼠（n = 166）随机分为六组。一组在研究开始时处死，四组进行卵巢切除，一组进行假手术（Sham）。给OVX大鼠皮下注射载体（veh）或氯膦酸盐，剂量分别为3、7或25 mg/kg，每周一次，共3个月，给Sham大鼠注射载体。在所有剂量水平下，氯膦酸盐均抑制股骨远端和第四腰椎椎体（L4）的小梁骨丢失，并减少骨吸收，尿脱氧吡啶啉排泄证明了这一点。氯膦酸盐的最低剂量在Sham/veh组水平上保留了血清骨钙素和L4继发性松质骨的骨内膜骨形成。OVX诱导的股骨干骨膜骨形成增加不受两个较小剂量氯膦酸盐的影响，但在最高剂量后降至Sham大鼠水平。给予3 mg/kg氯膦酸盐后，股骨皮质骨面积百分比和平均相对皮质厚度高于OVX/veh组。胫骨三点弯曲的最大负荷与胫骨灰重之间存在良好的正相关。氯膦酸盐治疗后发现新形成的松质骨和皮质骨的正常板层模式。未发现类骨质不良蓄积迹象或对长骨和腰椎机械强度有任何有害影响。
