Intermittent and continuous administration of the bisphosphonate ibandronate in ovariohysterectomized beagle dogs: Effects on bone morphometry and mineral properties
Intermittent and continuous administration of the bisphosphonate ibandronate in ovariohysterectomized beagle dogs: Effects on bone morphometry and mineral properties
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DOI：
10.1359/jbmr.1999.14.10.1768
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发表时间：
1999-10-01
影响因子：
6.2
通讯作者：
Malluche, HH
中科院分区：
文献类型：
--
作者：
Monier-Faugere, MC;Geng, ZP;Malluche, HH
双膦酸盐已成为绝经后骨质疏松症的一种有价值的治疗方法。双膦酸盐治疗通常伴随着治疗第一年骨矿物质密度（BMD）增加3-6%和骨转换减少。尽管骨转换率低，但BMD在治疗的第一年后继续缓慢增加。有证据表明，双膦酸盐不仅增加骨体积，而且还增强了二次矿化，本研究旨在解决这一问题，并比较连续和间歇双膦酸盐治疗对骨结构，形成和吸收的静态和动态参数以及骨矿物质特性的影响。60只犬行卵巢切除术（OVX），10只犬行假手术（Sham）。术后4个月，OVX犬分为6组（n = 10）。他们每天（7天中的5天）接受伊班膦酸盐，剂量为0，0.8，1.2，4.1和14 μ g/kg/天或间歇（65 μ g/kg/天，给药2周，停药11周）。假手术犬每天接受溶媒。在第4个月，OHX动物的骨体积显著减少（p < 0.05）。大于或等于4.1 μ g/kg/天的伊班膦酸盐剂量停止或完全逆转了骨丢失。OHX犬以14 μ g/kg/天的剂量给予伊班膦酸盐后，骨转换（活化频率）显著降低，与对照犬相比，这伴随着显著更高的晶体尺寸、更高的矿物质-基质比和更均匀的矿化骨基质。这一发现支持了这样的假设，即继发性矿化的增加在与双膦酸盐治疗相关的BMD增加中起作用。此外，间歇性和连续性治疗对骨体积的影响相似。然而，间歇性治疗对骨转换和骨矿物质性质更有节制。因此，间歇治疗可能是连续治疗的一种有吸引力的替代方法。
Bisphosphonates have emerged as a valuable treatment for postmenopausal osteoporosis. Bisphosphonate treatment is usually accompanied by a 3-6% gain in bone mineral density (BMD) during the first year of treatment and by a decrease in bone turnover. Despite low bone turnover, BMD continues to increase slowly beyond the first year of treatment. There is evidence that bisphosphonates not only increase bone volume but also enhance secondary mineralization, The present study was conducted to address this issue and to compare the effects of continuous and intermittent bisphosphonate therapy on static and dynamic parameters of bone structure, formation, and resorption and on mineral properties of bone. Sixty dogs were ovariohysterectomized (OHX) and 10 animals were sham-operated (Sham), Four months after surgery, OHX dogs were divided in six groups (n = 10 each). They received for 1 year ibandronate daily (5 out of 7 days) at a dose of 0, 0.8, 1.2, 4.1, and 14 mu g/kg/day or intermittently (65 mu g/kg/day, 2 weeks on, 11 weeks off). Sham dogs received vehicle daily. At month 4, there was a significant decrease in bone volume in OHX animals (p < 0.05), Doses of ibandronate greater than or equal to 4.1 mu g/kg/day stopped or completely reversed bone loss. Bone turnover (activation frequency) was significantly depressed in OHX dogs given ibandronate at the dose of 14 mu g/kg/day, This was accompanied by significantly higher crystal size, a higher mineral-to-matrix ratio, and a more uniformly mineralized bone matrix than in control dogs. This finding lends support to the hypothesis that an increase in secondary mineralization plays a role in gain in BMD associated with bisphosphonate treatment. Moreover, intermittent and continuous therapies had a similar effect on bone volume. However, intermittent therapy was more sparing on bone turnover and bone mineral properties. Intermittent therapy could therefore represent an attractive alternative approach to continuous therapy.