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雷洛昔芬而非阿伦膦酸盐可改善骨质疏松大鼠的骨整合受损。

Raloxifene but not alendronate can compensate the impaired osseointegration in osteoporotic rats.

机构信息

Department of Surgery and Integrated Clinic, Division of Oral and Maxillofacial Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil.

Department of Basic Sciences, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, 16015-050, Brazil.

出版信息

Clin Oral Investig. 2018 Jan;22(1):255-265. doi: 10.1007/s00784-017-2106-2. Epub 2017 Mar 29.

Abstract

OBJECTIVES

Alendronate and raloxifene, a bisphosphonate and a selective estrogen modulator, respectively, are established osteoporosis therapies. Current evidence suggests that simultaneous application of osteoporosis therapies modulates osseointegration. However, alendronate shows inconsistent findings and raloxifene has not been studied comprehensively. This study aimed to evaluate the bone dynamics and molecular and microstructural features at the peri-implant bone interface in osteoporotic rats.

MATERIALS AND METHODS

Thirty female rats underwent ovariectomy and were fed a diet low in calcium and phosphate and treated with alendronate or raloxifene for 30 days or underwent fictional ovariectomy surgery (SHAM) prior to implant insertion in the tibia; osteoporosis therapies continued thereafter. After 42 days, peri-implant bone was evaluated by histometric and micro-CT analysis. Fluorochrome incorporation and gene expression was determined to evaluate bone turnover.

RESULTS

We report here that alendronate had no impact on bone-to-implant contacts and the mineral apposition rate. The RANKL/OPG ratio and local bone volume, however, were increased compared to the untreated osteoporotic rats. Even though signaling to bone resorption activity through RANKL production was observed in the alendronate group, the blockade of bone resorption activity that occurs in decorrence to alendronate activity took place and resulted in an increase in bone volume. Raloxifene significantly increased osseointegration in osteoporotic rats, as indicated by bone-to-implant contacts, mineral apposition, and local bone volume. Raloxifene, however, had no considerable impact on the RANKL/OPG ratio compared to untreated osteoporotic rats. As expected, the SH group showed higher bone-to-implant contacts and mineral apposition rates than the untreated osteoporotic rats.

CONCLUSIONS

These findings suggest that raloxifene but not alendronate can compensate for the impaired osseointegration in osteoporotic rats.

CLINICAL RELEVANCE

Regarding the superiority of raloxifene observed in the improvement of bone dynamics response, this statement suggests that raloxifene could be a good option for osteoporosis patients in oral rehabilitation procedures.

摘要

目的

阿仑膦酸钠和雷洛昔芬分别是一种双膦酸盐和选择性雌激素受体调节剂,是已被确立的骨质疏松症治疗药物。目前的证据表明,同时应用骨质疏松症治疗药物会调节骨整合。然而,阿仑膦酸钠的研究结果并不一致,而雷洛昔芬则尚未得到全面研究。本研究旨在评估骨质疏松症大鼠种植体周围骨界面的骨动力学及分子和微观结构特征。

材料和方法

30 只雌性大鼠接受卵巢切除术,喂养低钙、低磷饮食,并接受阿仑膦酸钠或雷洛昔芬治疗 30 天,或在胫骨植入前接受假卵巢切除术(SHAM);此后继续骨质疏松症治疗。42 天后,通过组织学和微 CT 分析评估种植体周围骨。通过荧光标记掺入和基因表达来确定骨转换。

结果

本研究报告称,阿仑膦酸钠对骨与种植体的接触和矿化沉积率没有影响。然而,与未治疗的骨质疏松症大鼠相比,RANKL/OPG 比值和局部骨量增加。尽管阿仑膦酸钠组观察到通过 RANKL 产生向骨吸收活性的信号,但发生了阿仑膦酸钠活性引起的骨吸收活性的阻断,导致骨量增加。雷洛昔芬显著增加了骨质疏松症大鼠的骨整合,表现为骨与种植体的接触、矿化沉积和局部骨量增加。然而,与未治疗的骨质疏松症大鼠相比,雷洛昔芬对 RANKL/OPG 比值没有显著影响。如预期的那样,SH 组的骨与种植体接触和矿化沉积率高于未治疗的骨质疏松症大鼠。

结论

这些发现表明,雷洛昔芬而非阿仑膦酸钠可补偿骨质疏松症大鼠受损的骨整合。

临床意义

鉴于雷洛昔芬在改善骨动力学反应方面的优势,这一说法表明雷洛昔芬可能是骨质疏松症患者口腔康复治疗的一个不错选择。

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