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罗莫佐单抗联合活性维生素 D 对去卵巢大鼠骨折愈合的影响。

The effects of romosozumab combined with active vitamin D on fracture healing in ovariectomized rats.

机构信息

Oita University Hospital Rehabilitation Center, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-city, Oita, 879-5593, Japan.

School of Physical Therapy, Faculty of Rehabilitation, Reiwa Health Sciences University, 2-1-12 Wajirogaoka, Higashi-ku, Fukuoka, 811-0213, Japan.

出版信息

J Orthop Surg Res. 2022 Aug 12;17(1):384. doi: 10.1186/s13018-022-03276-1.

Abstract

BACKGROUND

In this study, we investigated the potential acceleration of fracture healing and bone mineral density-increasing effects of romosozumab and active vitamin D combination therapy for fractures in ovariectomized rats.

METHODS

Ovariectomy was performed on 40 24-week-old female Sprague-Dawley rats. After 8 weeks, the rats were subjected to periosteum removal and osteotomy of the femoral shaft followed by osteosynthesis with intramedullary nailing to create fracture models. The rats were then divided into four groups: C group (control), R group (receiving romosozumab at 25 mg/kg once a month via subcutaneous injection), VD group (receiving active vitamin D at 0.2 µg/kg twice a week via subcutaneous injection), and R + VD group. Further, 10 rats were included in a sham group. At 10 weeks after the intervention, both femurs were removed and blood samples were collected from all rats. Soft X-ray imaging was used to evaluate bone union, and microcomputed tomography (micro-CT) was used for bone morphometric evaluation. Toluidine blue staining was used for the histopathological evaluation of the undecalcified specimens, and bone turnover marker levels were measured using enzyme-linked immunosorbent assay.

RESULTS

Bone morphometry analysis via micro-CT revealed increased mineral density of the trabecular bone in the R + VD group femurs, demonstrating the effectiveness of romosozumab plus active vitamin D combination therapy. However, there were no differences in bone union evaluated using soft X-ray imaging, indicating no acceleration of fracture healing.

CONCLUSIONS

Although romosozumab and active vitamin D combination therapy increased trabecular bone volume, there was no evidence on its ability to accelerate fracture healing.

摘要

背景

本研究旨在探讨罗莫佐单抗与活性维生素 D 联合治疗对去卵巢大鼠骨折的潜在加速骨折愈合和增加骨密度的作用。

方法

对 40 只 24 周龄雌性 Sprague-Dawley 大鼠进行去卵巢手术。8 周后,大鼠接受骨膜剥离和股骨骨干截骨术,随后采用髓内钉内固定术进行骨折固定。将大鼠分为 4 组:C 组(对照组)、R 组(每月一次皮下注射罗莫佐单抗 25mg/kg)、VD 组(每周两次皮下注射活性维生素 D 0.2μg/kg)和 R+VD 组。另外,10 只大鼠设为假手术组。干预 10 周后,取出双侧股骨,采集所有大鼠的血样。采用软 X 射线成像评估骨愈合情况,采用微计算机断层扫描(micro-CT)进行骨形态计量学评估。采用甲苯胺蓝染色对未脱钙标本进行组织病理学评估,并采用酶联免疫吸附试验测定骨转换标志物水平。

结果

micro-CT 骨形态计量学分析显示,R+VD 组大鼠股骨的小梁骨矿物质密度增加,表明罗莫佐单抗联合活性维生素 D 治疗有效。然而,软 X 射线成像评估的骨愈合无差异,提示骨折愈合无加速。

结论

尽管罗莫佐单抗和活性维生素 D 联合治疗增加了小梁骨体积,但没有证据表明其有加速骨折愈合的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7473/9373334/3a581e71ba18/13018_2022_3276_Fig1_HTML.jpg

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