Regulation of Activating Blood and Dredging Collate Method on Serum Bone Resorption/Angiogenesis/Osteogenic Protein in Patients with Steriod-induced Osteonecrosis of Femoral Head Cystic Degeneration

doi:10.12114/j.issn.1007-9572.2023.0463

Chinese General Practice ›› 2024, Vol. 27 ›› Issue (12): 1504-1510.DOI: 10.12114/j.issn.1007-9572.2023.0463

• Original Research • Previous Articles Next Articles

Regulation of Activating Blood and Dredging Collate Method on Serum Bone Resorption/Angiogenesis/Osteogenic Protein in Patients with Steriod-induced Osteonecrosis of Femoral Head Cystic Degeneration

1. The Third Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510378, China
2. Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou 510378, China
3. Department of arthropathy, the Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510378, China

Received:2023-05-19 Revised:2023-10-18 Published:2024-04-20 Online:2024-01-23
Contact: WEI Qiushi

活血通络法对激素性股骨头坏死囊性变患者血清骨吸收/成血管/成骨蛋白调节作用的研究

1．510378　广东省广州市，广州中医药大学第三临床医学院
2．510378　广东省广州市，广东省中医骨伤研究院
3．510378　广东省广州市，广州中医药大学第三附属医院关节科

通讯作者: 魏秋实
作者简介:
作者贡献：何宪顺负责文章撰写；韦雨柔、何敏聪、林锟、田佳庆、詹芝玮负责统计学处理及表格的绘制与展示；林天烨、何晓铭负责数据的收集与整理；何伟、魏秋实提出主要研究目标，负责研究方案的构思、设计与论文修订；魏秋实负责文章的质量控制与审查。
基金资助:
国家自然科学基金面上项目(82274544); 国家自然科学基金青年项目(82004392); 广州中医药大学"双一流"与高水平大学学科协同创新团队培育项目(2021XK41); 广东省新黄埔中医药联合创新研究院2022年度第一批联合创新研究项目(2022IR012); 毕节市科学技术局2022年度"揭榜挂帅"项目(毕科合重大专项〔2022〕1号)

Abstract

Abstract:

Background

Steriod-induced osteonecrosis of femoral head (SIONFH) cystic degeneration have a "double-edged sword" effect. The method of activating blood and dredging collate is effective in the treatment of early SIONFH, but its regulatory effect on bone resorption/angiogenesis/osteogenic protein in cystic degeneration remains unclear.

Objective

To investigate the effect of activating blood and dredging collate method on serum bone resorption/angiogenesis/osteogenic protein in patients with cystic degeneration of SIONFH.

Methods

Sixty patients with SIONFH admitted to the Hip Joint Research Center of Guangzhou University of Traditional Chinese Medicine from January 2019 to January 2021 were included as the study subjects and divided into the control group and treatment group according to random number table method, with 30 cases in each group. Another 30 volunteers with normal physical examination in hospital at the same period and no history of hormone use were selected as the normal group. The treatment group was treated with Huoxuetongluo capsule (2 g/time, 3 times/day) and calcium carbonate (600 mg/time, 1 time/day), the control group was treated with the same amount of calcium carbonate, and the course of treatment of both groups was 12 months, simultaneously limiting weight-bearing on the affected limb. Fasting serum was collected, and the expression levels of nuclear factor κB receptor activating factor ligand (RANKL), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor A (VEGFA), osteoprotegerin (OPG) and cadherin-associated protein (CTNNB1) in serum were detected by enzyme-linked immunosorbent assay. The patients were followed up twice at the 6th and 12th month after discharge, and the collapse of femoral head was defined as the end event. Hip pain visual analogue score (VAS), hip function (Harris) score and necrotic area score were used to evaluate the efficacy.

Results

Baseline RANKL, PDGF-BB, OPG and CTNNB1 levels were compared among the three groups, and the differences were statistically significant (P<0.05). The results of intergroup comparison showed that RANKL and PDGF-BB in the control group and treatment group were higher than those in the normal group, while OPG and CTNNB1 were lower than those in the normal group, the difference was statistically significant (P<0.05). Repeated measurement ANOVA results showed that time and group had interaction effects on RANKL, PDGF-BB, VEGFA, OPG and CTNNB1 levels (P<0.05), time and group had significant main effect on RANKL, PDGF-BB, VEGFA, OPG and CTNNB1 levels (P<0.05). The level of RANKL in the treatment group was higher than that in the control group at the 6th month, the level of PDGF-BB in the treatment group was higher than that in the control group at the 12th month, and the levels of VEGFA, OPG and CTNNB1 were higher than those in the control group at the 6th and 12th months (P<0.05). At the 12 months after treatment, the hip VAS and necrotic area score of the treatment group were lower than those of the control group, and the hip Harris score was higher than that of the control group (P<0.05). The results of intragroup comparison showed that at 12 months after treatment, hip VAS and necrotic area score in the treatment group were lower than those before treatment, and hip Harris score was higher than that before treatment (P<0.05) ; hip VAS and hip Harris score in the control group were higher than those before treatment (P<0.05) .

Conclusion

Activating blood and dredging collate method can up-regulate the protein expression levels of RANKL, PDGF-BB, VEGFA, OPG and CTNNB1 in patients with SIONFH, effectively promote bone repair and improve clinical symptoms of SIONFH patients. It is hypothesized that this drug can promote the bone repair of cystic degeneration through the "bone resorption/angiogenesis/osteogenesis" repair network.

Key words: Femur head necrosis, Steriod-induced osteonecrosis of femoral head, Coxarthrosis, Activating blood dredging collaterals, Bone resorption/angiogenesis/osteogenic protein

摘要：

背景

激素性股骨头坏死（SIONFH）中囊性变具有"双刃剑"作用，活血通络法对早期激素性股骨头坏死疗效佳，但对囊性变骨吸收/成血管/成骨蛋白调节作用尚未明确。

目的

探讨活血通络法对激素性股骨头坏死囊性变患者血清骨吸收/成血管/成骨蛋白作用的影响。

方法

纳入2019年1月—2021年1月在广州中医药大学髋关节研究中心收治的60例SIONFH患者为研究对象，按随机数字表法分成两组，对照组和治疗组各30例。另选取同时期在医院体检正常且无激素使用史30例志愿者作为正常组。治疗组给予活血通络胶囊（2 g/次，3次/d）及碳酸钙（600 mg/次，1次/d）治疗，对照组给予等量碳酸钙治疗，两组患者疗程均为12个月，同时患肢加以限制性负重。采集空腹血清，采用酶联免疫吸附试验检测血清核因子κB受体活化因子配体（RANKL）、血小板衍生生长因子-BB（PDGF-BB）、血管内皮生长因子A（VEGFA）、骨保护素（OPG）、钙黏蛋白相关蛋白（CTNNB1）的表达水平，以门诊复诊方式分别于患者出院后第6、12个月进行2次随访，以股骨头塌陷定义为终点事件。以髋关节疼痛视觉模拟评分（VAS）、髋关节功能（Harris）评分和坏死面积评分进行疗效评估。

结果

3组研究对象基线RANKL、PDGF-BB、OPG、CTNNB1水平比较，差异均有统计学意义（P<0.05），组间比较结果显示，对照组、治疗组RANKL、PDGF-BB均高于正常组，OPG、CTNNB1均低于正常组（P<0.05）。重复测量方差分析结果示，时间和组别对RANKL、PDGF-BB、VEGFA、OPG、CTNNB1水平存在交互作用（P<0.05），时间和组别对RANKL、PDGF-BB、VEGFA、OPG、CTNNB1水平主效应显著（P<0.05）。其中第6个月治疗组RANKL水平高于对照组，第12个月治疗组PDGF-BB水平高于对照组，第6、12个月VEGFA、OPG、CTNNB1水平高于对照组（P<0.05）。治疗后第12个月治疗组髋关节VAS评分、坏死面积评分低于对照组，髋关节Harris评分高于对照组（P<0.05）。组内比较结果显示，治疗后第12个月治疗组髋关节VAS评分、坏死面积评分低于治疗前，髋关节Harris评分高于治疗前（P<0.05），对照组髋关节VAS评分、髋关节Harris评分高于治疗前（P<0.05）。

结论

活血通络法能上调激素性股骨头坏死患者RANKL、PDGF-BB、VEGFA、OPG和CTNNB1蛋白表达水平，有效促进SIONFH患者骨修复及改善临床症状，推测该疗法通过"骨吸收/成血管/成骨"三元修复网络促进囊性变骨修复作用。

关键词: 股骨头坏死, 激素性股骨头坏死, 髋关节病, 活血通络, 骨吸收/成血管/成骨蛋白

HE Xianshun,WEI Yurou,HE Mincong, et al. Regulation of Activating Blood and Dredging Collate Method on Serum Bone Resorption/Angiogenesis/Osteogenic Protein in Patients with Steriod-induced Osteonecrosis of Femoral Head Cystic Degeneration[J]. Chinese General Practice, 2024, 27(12): 1504-1510. DOI: 10.12114/j.issn.1007-9572.2023.0463.
何宪顺,韦雨柔,何敏聪等. 活血通络法对激素性股骨头坏死囊性变患者血清骨吸收/成血管/成骨蛋白调节作用的研究[J]. 中国全科医学, 2024, 27(12): 1504-1510. DOI: 10.12114/j.issn.1007-9572.2023.0463.

Figures/Tables 3

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组别	例数	年龄（岁）	性别（男/女）	身高（cm）	体质量（kg）
正常组	30	45.4±13.5	20/10	163.2±9.1	63.6±10.3
对照组	30	39.9±14.8	24/6	165.0±8.9	57.9±9.9
治疗组	30	47.8±13.6	24/6	168.4±8.0	63.3±10.3
F（χ²）值		2.52	1.93^a	2.78	2.99
P值		0.087	0.382	0.068	0.056

组别	例数	年龄（岁）	性别（男/女）	身高（cm）	体质量（kg）
正常组	30	45.4±13.5	20/10	163.2±9.1	63.6±10.3
对照组	30	39.9±14.8	24/6	165.0±8.9	57.9±9.9
治疗组	30	47.8±13.6	24/6	168.4±8.0	63.3±10.3
F（χ²）值		2.52	1.93^a	2.78	2.99
P值		0.087	0.382	0.068	0.056

组别	例数	RANKL			PDGF-BB
组别	例数	基线	第6个月	第12个月	基线	第6个月	第12个月
正常组	30	18.27±5.33			61.00±8.40
对照组	30	38.74±4.00^a	25.11±5.11	22.07±4.54	73.04±10.65^a	97.69±5.65	109.76±9.10
治疗组	30	41.47±3.44^a	58.78±5.70^b	25.16±7.09	70.29±8.37^a	100.56±9.10	141.78±12.89^b
F值		F_交互=180.5，F_时间=233.1，F_组间=297.4			F_交互=57.3，F_时间=481.5，F_组间=56.6
P值		P_交互<0.001，P_时间<0.001，P_组间<0.001			P_交互<0.001，P_时间<0.001，P_组间<0.001
组别	VEGFA			OPG			CTNNB1
组别	基线	第6个月	第12个月	基线	第6个月	第12个月	基线	第6个月	第12个月
正常组	1 973.70±283.10			192.70±13.80			61.97±20.59
对照组	1932.97±290.10	2 472.16±200.86	2 347.19±124.55	155.08±17.77^a	210.60±11.62	234.22±14.47	32.77±15.05^a	79.54±13.47	67.41±12.78
治疗组	2 039.49±260.47	3 144.00±150.10^b	3 510.47±184.5^b	159.02±14.33^a	261.88±20.40^b	297.79±10.80^b	34.56±11.78^a	117.79±10.44^b	91.30±15.82^b
F值	F_交互=79.9，F_时间=379.8，F_组间=450.7			F_交互=63.7，F_时间=815.3，F_组间=302.3			F_交互=28.4，F_时间=375.1，F_组间=114.7
P值	P_交互<0.001，P_时间<0.001，P_组间<0.001			P_交互<0.001，P_时间<0.001，P_组间<0.001			P_交互<0.001，P_时间<0.001，P_组间<0.001

组别	例数	RANKL			PDGF-BB
组别	例数	基线	第6个月	第12个月	基线	第6个月	第12个月
正常组	30	18.27±5.33			61.00±8.40
对照组	30	38.74±4.00^a	25.11±5.11	22.07±4.54	73.04±10.65^a	97.69±5.65	109.76±9.10
治疗组	30	41.47±3.44^a	58.78±5.70^b	25.16±7.09	70.29±8.37^a	100.56±9.10	141.78±12.89^b
F值		F_交互=180.5，F_时间=233.1，F_组间=297.4			F_交互=57.3，F_时间=481.5，F_组间=56.6
P值		P_交互<0.001，P_时间<0.001，P_组间<0.001			P_交互<0.001，P_时间<0.001，P_组间<0.001
组别	VEGFA			OPG			CTNNB1
组别	基线	第6个月	第12个月	基线	第6个月	第12个月	基线	第6个月	第12个月
正常组	1 973.70±283.10			192.70±13.80			61.97±20.59
对照组	1932.97±290.10	2 472.16±200.86	2 347.19±124.55	155.08±17.77^a	210.60±11.62	234.22±14.47	32.77±15.05^a	79.54±13.47	67.41±12.78
治疗组	2 039.49±260.47	3 144.00±150.10^b	3 510.47±184.5^b	159.02±14.33^a	261.88±20.40^b	297.79±10.80^b	34.56±11.78^a	117.79±10.44^b	91.30±15.82^b
F值	F_交互=79.9，F_时间=379.8，F_组间=450.7			F_交互=63.7，F_时间=815.3，F_组间=302.3			F_交互=28.4，F_时间=375.1，F_组间=114.7
P值	P_交互<0.001，P_时间<0.001，P_组间<0.001			P_交互<0.001，P_时间<0.001，P_组间<0.001			P_交互<0.001，P_时间<0.001，P_组间<0.001

组别	例数	髋关节VAS评分[M（P₂₅，P₇₅）]				髋关节Harris评分				坏死面积评分
组别	例数	基线	第12个月	Z值	P值	基线	第12个月	t_配对值	P值	基线	第12个月	t_配对值	P值
对照组	30	2.00（1.00，3.00）	2.50（1.87，3.00）	-2.52^a	<0.05	78.73±4.52	81.43±4.94	-4.60	<0.05	2.32±0.86	1.91±0.78	1.74	0.095
治疗组	30	1.50（0.75，3.00）	1.00（0.50，1.50）	-2.45^a	<0.05	80.47±3.43	86.80±4.28	-9.39	<0.05	2.57±0.62	1.37±0.77	5.73	<0.05
t（Z）值		-0.22^a	-4.65^a			1.83	4.62			1.49	3.05
P值		0.826	<0.001			0.073	<0.001			0.138	0.003

Regulation of Activating Blood and Dredging Collate Method on Serum Bone Resorption/Angiogenesis/Osteogenic Protein in Patients with Steriod-induced Osteonecrosis of Femoral Head Cystic Degeneration

活血通络法对激素性股骨头坏死囊性变患者血清骨吸收/成血管/成骨蛋白调节作用的研究

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