Effects of tiludronate on bone mass, structure, and turnover at the epiphyseal, primary, and secondary spongiosa in the proximal tibia of growing rats after sciatic neurectomy
Effects of tiludronate on bone mass, structure, and turnover at the epiphyseal, primary, and secondary spongiosa in the proximal tibia of growing rats after sciatic neurectomy
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替鲁膦酸钠对坐骨神经切除术后生长大鼠胫骨近端骨骺、初级和次级海绵体骨量、结构和周转的影响
DOI：
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发表时间：
1994
影响因子：
6.2
通讯作者：
Katsumi Suzuki
中科院分区：
文献类型：
--
作者：
H. Murakami;Toshitaka Nakamura;H. Tsurukami;M. Abe;A. Barbier;Katsumi Suzuki
为了评估替鲁膦酸盐对固定大鼠胫骨松质骨区域的质量、结构和转换的影响，我们进行了为期4周的给药实验。对84只Sprague-道利大鼠（5周龄）的右后肢进行神经切除或假手术。将动物分为7组（每组n = 12）;第1组为假手术组，第2 - 7组为神经切除组。在整个实验期间，第1组和第2组仅给予溶媒（蒸馏水），第3组、第4组和第5组分别以25、50和100 mg/kg体重（BW）/天的剂量经口给予替鲁膦酸盐。第6组仅在前2周给予100 mg/kg BW/天的药剂，第7组仅在前2周给予溶媒，然后在最后2周给予100 mg/kg BW/天的药剂。进行四环素标记后，从动物中取出右睾丸，并进行处理以产生未脱钙切片。在胫骨近端的骨骺、原发性和继发性松质骨中进行组织形态测定。在第2组中，松质骨体积（BV/TV）和松质骨数量（Tb.N）在原发性和继发性松质骨中显著减少，但在骨骺松质骨中没有发生这种情况。次级松质骨中类骨质表面积（OS/BS）减少，破骨细胞表面积（OC.S/BS）增加。替鲁膦酸盐通过降低破骨细胞表面参数（Oc.S/BS）和破骨细胞数量（Oc.N/BS）来增加初级松质骨的BV/TV和Tb.N。该区域的类骨质表面未被药物降低。在第4组和第5组中，替鲁膦酸盐通过降低OS/BS和OC.S/BS来防止继发性松质骨的骨丢失。第6组的BV/TV维持在第1组的水平，但Oc.S/BS和Oc.N/BS升高。在二级松质中，骨量得到保留，并且这些参数的降低得到维持。然而，在第7组中，由于骨吸收减少，原发性海绵体中的BV/TV增加;然而，在继发性海绵体中，BV/TV降低，并且在这些生长动物的实验结束时，小梁转换没有减少。替鲁膦酸盐未降低矿物质沉积率。这项研究清楚地表明，这种药物通过抑制再吸收来防止固定骨丢失。组织形态计量学数据表明：（1）替鲁膦酸盐在给药后早期开始在原发性海绵体中发挥作用，而在继发性海绵体中则较晚;（2）骨基质参与了该双膦酸盐的抗再吸收作用。
To evaluate the effects of tiludronate on the mass, structure, and turnover of cancellous bone regions in immobilized rat tibiae, we performed a 4 week dosing experiment. The right hindlimbs of 84 Sprague‐Dawley rats (5 weeks old) were neurectomized or sham operated. Animals were assigned to seven groups (n = 12 each); group 1 was sham operated, and groups 2‐7 were neurectomized. Groups 1 and 2 were given vehicle only (distilled water), and groups 3, 4, and 5 were given tiludronate orally at doses of 25, 50, and 100 mg/kg body weight (BW)/day, respectively, throughout the experimental period. Group 6 was given 100 mg/kg BW/day of the agent for the first 2 weeks only, and group 7 received vehicle only for the first 2 weeks and then 100 mg/kg BW/day of the agent for the last 2 weeks. After tetracycline labeling was performed, the right tibiae were removed from the animals and processed to yield undecalcified sections. Histomorphometry was performed in the epiphyseal, primary, and secondary spongiosa of the proximal tibia. In group 2, trabecular bone volume (BV/TV) and trabecular number (Tb.N) were significantly decreased in the primary and secondary spongiosae, but this did not occur in the epiphyseal spongiosa. Osteoid surface (OS/BS) was decreased and osteoclast surface (Oc.S/BS) was increased in the secondary spongiosa. Tiludronate increased BV/TV and Tb.N in the primary spongiosa by reducing the values for the parameters of osteoclast surface (Oc.S/BS) and osteoclast number (Oc.N/BS). Osteoid surface in this region was not decreased by the agent. In groups 4 and 5, tiludronate prevented bone loss in the secondary spongiosa by reducing both OS/BS and Oc.S/BS. In group 6, BV/TV in the primary spongiosa was maintained at the level of group 1, but Oc.S/BS and Oc.N/BS were elevated. In the secondary spongiosa, bone mass was preserved and the reduction in these parameters was maintained. In group 7, however, BV/TV was increased in the primary spongiosa as a result of a reduction in osteoclastic resorption; in the secondary spongiosa, however, BV/TV was decreased and trabecular turnover was not reduced at the end of the experiment in these growing animals. Mineral apposition rates were not reduced by tiludronate. This study clearly demonstrated that this agent prevented immobilization bone loss by inhibiting resorption. The histomorphometric data suggest that (1) tiludronate begins to act early after administration in the primary spongiosa and rather late in the secondary spongiosa, and (2) the bone matrix is involved in the antiresorbing action of this bisphosphonate.
影响因子：
15.9
作者：
CARANO, A;TEITELBAUM, SL;BLAIR, HC
通讯作者：
BLAIR, HC
前列腺素 E2 可防止废用引起的皮质骨丢失。
影响因子：
4.1
作者：
Jee,WS;Akamine,T;Ke,HZ;Li,XJ;Tang,LY;Zeng,QQ
通讯作者：
Zeng,QQ