Ammann P, Rizzoli R, Caverzasio J, Shigematsu T, Slosman D, Bonjour J P
Department of Medicine, University Hospital, Geneva, Switzerland.
J Bone Miner Res. 1993 Dec;8(12):1491-8. doi: 10.1002/jbmr.5650081212.
Bone resorption inhibitors, such as bisphosphonates, are potentially useful in treatments aimed at increasing bone mass. Among bisphosphonates, tiludronate has proven efficacious in preventing bone loss in postmenopausal women. However, it is not clearly established whether bisphosphonates are more potent when given intermittently or continuously. We investigated the effects of tiludronate on (1) retinoid-stimulated bone resorption in thyroparathyroidectomized rats, (2) calcium balance in intact rats, and (3) bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry at the levels of the lumbar spine, tail, and tibia in 6-month-old rats made osteoporotic by ovariectomy (OVX), in which an intermittent cyclic schedule of treatment was compared to continuous administration. Tiludronate induced a dose-dependent decrease in retinoid-stimulated bone resorption. It increased the intestinal absorption and body retention of calcium. In OVX rats it caused a time- and dose-dependent increase in BMD at the level of the three investigated sites, the effects being maintained for at least 8 weeks after the end of therapy. Continuous and intermittent cyclic regimens appeared to induce similar increases in BMD. These results indicate that tiludronate is efficacious in decreasing bone resorption and increasing calcium balance and bone mineral density in rats.
骨吸收抑制剂，如双膦酸盐，在旨在增加骨量的治疗中可能有用。在双膦酸盐中，替鲁膦酸盐已被证明对预防绝经后妇女的骨质流失有效。然而，尚不清楚双膦酸盐间歇性给药还是连续给药更有效。我们研究了替鲁膦酸盐对以下方面的影响：（1）甲状旁腺切除大鼠中类维生素A刺激的骨吸收；（2）完整大鼠的钙平衡；（3）通过双能X线吸收法测量6个月大卵巢切除（OVX）致骨质疏松大鼠腰椎、尾部和胫骨水平的骨矿物质密度（BMD），并比较了间歇性循环给药方案与连续给药的效果。替鲁膦酸盐可使类维生素A刺激的骨吸收呈剂量依赖性降低。它增加了钙的肠道吸收和体内潴留。在OVX大鼠中，它使三个研究部位的BMD呈时间和剂量依赖性增加，治疗结束后效果至少维持8周。连续和间歇性循环给药方案似乎能使BMD产生相似的增加。这些结果表明，替鲁膦酸盐在降低大鼠骨吸收、增加钙平衡和骨矿物质密度方面是有效的。
