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利塞膦酸钠的第三代双膦酸盐对大鼠骨质疏松性骨折的动态影响,为临床应用提供指导。

Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance.

机构信息

Department of Orthopaedics, Children's Hospital of Shanghai, Shanghai, China.

Department of Anesthesiology, Children's Hospital of Shanghai, Shanghai, China.

出版信息

Orthop Surg. 2021 Dec;13(8):2433-2441. doi: 10.1111/os.13158. Epub 2021 Oct 21.

Abstract

OBJECTIVE

To better understand the risks of bisphosphonates in order to develop guidance for appropriate clinical usage, to compared femoral fracture healing at different time points and to explore the effects of Residronate on fracture healing.

METHODS

Osteoporosis model was achieved by ovariectomy surgery, followed by surgical incision of left femoral shaft 4 weeks after ovariectomy surgery. Three days after fracture surgery, risedronateor saline was fed by intragastric administration. X ray examination was used to check the callus formation, Bone Mineral Density (BMD), Bone Mineral Content (BMC), biomechanical, imaging and micromorphological of bone tissue as well as the trabecular bone parameters were all examined. The femoral pathology tissue of each rat was used to analyze trabecular bone parameters, including trabecular bone volume/tissue volume (Tb. BV/TV), bone surface to tissue volume ratio (BS/TV), trabecular bone mineral density (Tb. BMD), trabecular bone number (Tb. N), trabecular bone thickness (Tb. Th) and small bone Trabecular bone space (Tb. Sp).

RESULTS

Via X-ray and pathologically, risedronate treatment promoted the callus forming at the fracture site during the following 6 weeks after osteoporotic fracture by X-ray (P < 0.01), increased the local bone mineral density (P < 0.01), and accelerated the fracture healing during the first 3 weeks (P <0.01), but delayed facture healing in the later 3 weeks (P < 0.01). Risedronate increased the bone continuity of fracture at 7th week, but this phenomenon was not found at the 10th week (P < 0.01). Delayed fracture healing occurred locally at the fracture site. At 7th week, Risedronate may promote cartilage cells proliferating at fracture site, increase the dense of bone trabeculae and the connection of bone trabeculae, thicken the bone cortex showing better fracture healing than OPF-Saline groups (P < 0.01). However, these parameter did not continue during the 7th and 10th weeks. Comparing the first and the later 3 weeks, the rats in group Osteoporotic Fracture-Risedronate (OPF-RD) accelerated the local fracture healing in the first 3 weeks but not in the last 3 weeks, which is consistent for the BMD and BMC among each group (P < 0.05). Through evaluation of bone mineral density and bone mineral content, risedronate dramatically increased the BMD at the fracture site and resulted in reduction of BMC by risedronate at the fracture site (P < 0.05) among each group still exist, indicating dramatic (P < 0.05). Through load testing, Risedronate increased the structural strength and mechanical indexes of the new callus (P < 0.01).

CONCLUSION

Risedronate can improve the structural strength and mechanical index of newborn callus. Longer than 7 weeks usage of third generation bisphosphonate of risedronate does not contribute to osteoporotic fracture.

摘要

目的

为了更好地了解双膦酸盐的风险,以便为临床应用提供指导,比较不同时间点股骨骨折的愈合情况,并探讨雷奈酸锶对骨折愈合的影响。

方法

通过卵巢切除术建立骨质疏松模型,在卵巢切除术后 4 周进行左侧股骨骨干切开术。骨折手术后 3 天,通过灌胃给予雷奈酸锶或生理盐水。使用 X 射线检查来检查骨痂形成、骨密度(BMD)、骨矿物质含量(BMC)、生物力学、骨组织成像和微观形态以及小梁骨参数。对每个大鼠的股骨病理组织进行分析,包括小梁骨体积/组织体积(Tb. BV/TV)、骨表面与组织体积比(BS/TV)、小梁骨密度(Tb. BMD)、小梁骨数量(Tb. N)、小梁骨厚度(Tb. Th)和小骨小梁空间(Tb. Sp)。

结果

通过 X 射线和病理检查,雷奈酸锶治疗在骨质疏松性骨折后 6 周内通过 X 射线促进了骨折部位的骨痂形成(P<0.01),增加了局部骨密度(P<0.01),并在最初的 3 周内加速了骨折愈合(P<0.01),但在随后的 3 周内延迟了骨折愈合(P<0.01)。雷奈酸锶在第 7 周增加了骨折部位的骨连续性,但在第 10 周未发现这种现象(P<0.01)。骨折部位局部出现延迟愈合。在第 7 周,雷奈酸锶可能促进骨折部位的软骨细胞增殖,增加骨小梁的密度和连接,使骨皮质增厚,显示出比 OPF-生理盐水组更好的骨折愈合(P<0.01)。然而,这些参数在第 7 周和第 10 周并未持续。比较前 3 周和后 3 周,骨质疏松性骨折-雷奈酸锶组(OPF-RD)大鼠在前 3 周加速了局部骨折愈合,但在后 3 周没有加速,各组之间的骨密度和 BMC 也存在差异(P<0.05)。通过骨密度和骨矿物质含量的评估,雷奈酸锶显著增加了骨折部位的骨密度,并导致骨折部位的 BMC 减少(P<0.05),各组之间仍存在差异,表明差异显著(P<0.05)。通过负荷试验,雷奈酸锶增加了新生骨痂的结构强度和力学指标(P<0.01)。第三代双膦酸盐雷奈酸锶的使用时间超过 7 周对骨质疏松性骨折没有益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c9c/8654647/e469ad35b2f7/OS-13-2433-g003.jpg

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