Iwamoto Jun, Takeda Tsuyoshi, Sato Yoshihiro, Shen Chwan-Li, Yeh James K
Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan.
Exp Anim. 2006 Oct;55(5):457-66. doi: 10.1538/expanim.55.457.
The purposes of the present study were to differentiate the effects of pre-surgery treatment with risedronate and post-surgery treatment with a reduced dosing frequency of risedronate on trabecular bone loss in ovariectomized rats and to determine whether post-surgery treatment with a reduced dosing frequency of risedronate would have a beneficial effect on trabecular bone loss after pre-surgery treatment with risedronate by means of bone histomorphometric analysis. The short-term experiment (6 weeks) was performed on fifty, 4-month-old, female Sprague-Dawley rats randomized into five groups (n=10 in each group). Forty rats were treated with vehicle or risedronate for 4 weeks before ovariectomy (OVX), and then treated with either vehicle or risedronate for 2 weeks following OVX (the Vehicle-OVX-Vehicle [OVX control], Vehicle-OVX-Risedronate [post-OVX treatment with risedronate], Risedronate-OVX-Vehicle [pre-OVX treatment with risedronate], and Risedronate-OVX-Risedronate [continuous treatment with risedronate] groups). The remaining 10 rats were treated with vehicle for 6 weeks, with a sham operation performed 4 weeks after the start of the experiment (the Vehicle-Sham-Vehicle [Sham control] group). During the 4 weeks prior to surgery, risedronate was administered five times a week subcutaneously at a dose of 2.5 microg /kg body weight, and during the 2 weeks after surgery, the dosing frequency was reduced to twice a week. The long-term experiment (10 weeks) had the same design as the short-term one, except that the post-OVX treatment was 6 weeks. In the short-term experiment, both pre- and post-OVX treatments with risedronate prevented trabecular bone loss of the proximal tibial metaphysis 2 weeks after OVX. In long-term experiment, however, pre- and post-OVX treatments with risedronate attenuated trabecular bone loss until 6 weeks after OVX, with pre-OVX treatment having a less pronounced effect than post-OVX treatment. In the short- and long-term experiments, pre-and post-OVX treatments had an additive effect on trabecular bone mass. The present study has shown the efficacy of pre-OVX treatment with risedronate or post-OVX treatment with a low dosing frequency of risedronate for preventing trabecular bone loss early after OVX. Post-OVX treatment with a low dosing frequency of risedronate was beneficial for attenuating trabecular bone loss late after OVX. Treatment with risedronate before OVX had an additive effect on trabecular bone mass with the treatment after OVX, suggesting that treatment with a low dosing frequency of risedronate might be acceptable for reducing OVX-induced trabecular bone loss after treatment with risedronate prior to OVX.
本研究的目的是区分术前使用利塞膦酸盐治疗和术后降低利塞膦酸盐给药频率治疗对去卵巢大鼠小梁骨丢失的影响，并通过骨组织形态计量学分析确定术后降低利塞膦酸盐给药频率治疗在术前使用利塞膦酸盐治疗后对小梁骨丢失是否具有有益作用。对50只4月龄雌性Sprague-Dawley大鼠进行短期实验（6周），随机分为五组（每组n = 10）。40只大鼠在去卵巢（OVX）前用赋形剂或利塞膦酸盐治疗4周，然后在OVX后用赋形剂或利塞膦酸盐治疗2周（分别为赋形剂-OVX-赋形剂组[OVX对照组]、赋形剂-OVX-利塞膦酸盐组[OVX后用利塞膦酸盐治疗组]、利塞膦酸盐-OVX-赋形剂组[OVX前用利塞膦酸盐治疗组]和利塞膦酸盐-OVX-利塞膦酸盐组[持续用利塞膦酸盐治疗组]）。其余10只大鼠用赋形剂治疗6周，在实验开始4周后进行假手术（赋形剂-假手术-赋形剂组[假手术对照组]）。在手术前的4周内，利塞膦酸盐以2.5μg /kg体重的剂量每周皮下注射5次，在手术后的2周内，给药频率降至每周2次。长期实验（10周）的设计与短期实验相同，只是OVX后的治疗时间为6周。在短期实验中，术前和术后使用利塞膦酸盐治疗均可预防OVX后2周近端胫骨干骺端的小梁骨丢失。然而，在长期实验中，术前和术后使用利塞膦酸盐治疗可减轻OVX后6周内的小梁骨丢失，术前治疗的效果不如术后治疗明显。在短期和长期实验中，术前和术后治疗对小梁骨量具有累加效应。本研究表明，术前使用利塞膦酸盐治疗或术后低剂量频率使用利塞膦酸盐治疗对预防OVX后早期小梁骨丢失有效。术后低剂量频率使用利塞膦酸盐治疗有利于减轻OVX后期的小梁骨丢失。OVX前使用利塞膦酸盐治疗与OVX后治疗对小梁骨量具有累加效应，这表明在OVX前使用利塞膦酸盐治疗后，低剂量频率使用利塞膦酸盐治疗对于减少OVX诱导的小梁骨丢失可能是可接受的。
