Efficacy and Safety of Antibiotic Bone Cement Combined with Vacuum Sealing Drainage for Diabetic Foot: a Meta-analysis

doi:10.12114/j.issn.1007-9572.2025.0102

Abstract

Abstract:

Background

Diabetic foot ulcers (DFU) represent prevalent chronic wounds with significant negative impacts on patients' health and socioeconomic status. Antibiotic bone cement (ABC) has emerged as a therapeutic option, though its efficacy and safety require comprehensive evaluation.

Objective

To perform a meta-analysis of randomized controlled trials (RCT) assessing the efficacy and safety of ABC for DFU, thereby providing evidence-based guidance for clinical practice.

Methods

We systematically searched CNKI, Wanfang Data, VIP, China Biomedical Literature Database, PubMed, Cochrane Library, Embase, and Web of Science for RCT published until January 2025. Thirteen RCT involving 843 patients were included. The intervention group received ABC combined with vacuum sealing drainage (VSD), while controls received VSD alone. Outcomes included wound healing time, clinical efficacy rate, bacterial clearance time, hospital stay, surgical frequency, amputation rate, visual analogue scale (VAS) scores, and adverse events. RevMan 5.3 was used with random-effects models for heterogeneous data.

Results

The meta-analysis demonstrated that combined ABC therapy significantly: reduced wound healing time (MD=-14.46, 95%CI=-19.69 to -9.23; P<0.05), increased clinical efficacy rates (OR=7.81, 95%CI=3.94 to 17.48, P<0.05), shortened bacterial clearance time (MD=-4.04, 95%CI=-5.13 to -2.94, P<0.05), decreased positive bacterial cultures at 1-week post-treatment (OR=0.27, 95%CI=0.14 to 0.50, P<0.05), lowered amputation rates (OR=0.14, 95%CI=0.03 to 0.62, P=0.01), reduced surgical frequency (MD=-1.77, 95%CI=-2.52 to -1.03, P<0.05); decreased VAS scores (MD=-1.96, 95%CI=-2.35 to -0.57, P<0.05). Additionally, no adverse events were reported across the included studies. For wound healing time, it was divided into Wagner 5 group and non-Wagner 5 group according to different research subjects, and divided into combination group and monotherapy group according to different types of antibiotics. The results of the non-Wagner 5 group showed that ABC combined with VSD treatment could significantly shorten the wound healing time of DFU patients compared with VSD treatment alone (MD=-6.31, 95%CI=-7.88 to -4.74, P<0.05); The results of the Wagner grade 5 group showed that there was no significant difference between the experimental group and the control group (MD=-8.02, 95%CI=-20.11 to 4.07, P=0.19). The results of the antibiotic alone group showed that ABC combined with VSD treatment could shorten the wound healing time of DFU patients compared with VSD alone (MD=-4.52, 95%CI=-5.81 to -3.23, P<0.05). The results of the combination antibiotic group showed that ABC combined with VSD treatment could significantly shorten the wound healing time of DFU patients compared with VSD alone (MD=-14.21, 95%CI=-18.20 to -10.21, P<0.05). For the length of hospitalization, according to the age of the study subjects, they were divided into the average age greater than 60 years old group and the average age less than 60 years group. The results of the mean age group greater than 60 years showed that ABC combined with VSD treatment could shorten the hospital stay of DFU patients compared with VSD treatment alone (MD=-6.82, 95%CI=-10.93 to -2.71, P=0.001). The results of the average age less than 60 years old group showed that there was no significant difference between the experimental group and the control group (MD=-5.11, 95%CI=-17.78 to 7.56, P=0.45). For the number of surgeries, according to the wound treatment methods, it is divided into a group with skin graft and a group without skin grafting. The results of the no skin graft group showed that ABC combined with VSD treatment could reduce the number of surgeries in DFU patients compared with VSD treatment alone (MD=-1.79, 95%CI=-2.13 to -1.46, P<0.05). The results of the skin graft group showed that ABC combined with VSD treatment could significantly reduce the number of surgeries in patients with DFU compared with VSD treatment alone (MD=-1.89, 95%CI=-3.27 to -0.50, P=0.008). Sensitivity analysis was performed and the results of this study were found.

Conclusion

In this study, ABC combined with VSD is a safe and effective therapy for DFU, especially for non-Wagner grade 5 patients and the elderly, and the combination of antibiotics and skin grafting can further enhance the efficacy.

Key words: Diabetic foot, Foot ulcer, diabetic, Cementoplasty, Antibiotic bone cements, Negative-pressure wound therapy, Vaccum sealing drainage, Wound healing, Meta-analysis

摘要：

背景

糖尿病足溃疡（DFU）是常见的慢性难愈性创面，给患者的健康和经济带来了严重的负面影响。近年来，抗生素骨水泥（ABC）被逐渐应用于DFU的治疗。然而，其有效性和安全性尚未得到充分评估。

目的

本研究通过Meta分析整合随机对照试验（RCT）数据，评估ABC治疗DFU的有效性及安全性，从而为临床治疗提供方向。

方法

计算机检索中国知网、万方数据知识服务平台、维普网、中国生物医学文献数据库、PubMed、Cochrane Library、Embase、Web of Science等数据库，检索建库至2025年1月发表的ABC治疗糖尿病足的RCT。由2名研究者独立筛选文献并提取数据，最终纳入13项RCT，包含843例患者，试验组为ABC联合负压封闭引流技术（VSD）治疗，对照组为单纯的VSD治疗。采用RevMan 5.3软件对创面愈合时间、临床有效率、细菌转阴天数、住院时间、手术次数、截肢率、视觉模拟评分量表（VAS）评分、治疗1周后细菌培养阳性率、不良反应进行Meta分析，异质性较高时采用随机效应模型。

结果

Meta分析显示，联合ABC治疗能显著缩短DFU的创面愈合时间（MD=-14.46，95%CI=-19.69~-9.23，P<0.05），提高临床有效率（OR=7.81，95%CI=3.94~17.48，P<0.05），缩短细菌转阴天数（MD=-4.04，95%CI=-5.13~-2.94，P<0.05），减少治疗1周后细菌培养阳性结果的发生（OR=0.27，95%CI=0.14~0.50，P<0.05），降低截肢率（OR=0.14，95%CI=0.03~0.62，P=0.01），减少手术次数（MD=-1.77，95%CI=-2.52~-1.03，P<0.05），降低VAS评分（MD=-1.96，95%CI=-1.96~-0.57，P<0.05）。同时，所有纳入的研究中ABC治疗DFU均未声明发生不良反应。对于创面愈合时间，根据研究对象的不同分为Wagner 5级组和非Wagner 5级组，又根据负载抗生素的种类不同分为联用组和单用组。非Wagner 5级组结果显示，与单纯的VSD治疗相比，ABC联合VSD治疗能显著缩短DFU患者的创面愈合时间（MD=-6.31，95%CI=-7.88~-4.74，P<0.05）；Wagner 5级组的结果显示，试验组与对照组比较，差异无统计学意义（MD=-8.02，95%CI=-20.11~4.07，P=0.19）。单用抗生素组的结果显示，与单纯的VSD治疗相比，ABC联合VSD治疗能缩短DFU患者的创面愈合时间（MD=-4.52，95%CI=-5.81~-3.23，P<0.05）；联用抗生素组的结果显示，与单纯的VSD治疗相比，ABC联合VSD治疗能显著缩短DFU患者的创面愈合时间（MD=-14.21，95%CI=-18.20~-10.21，P<0.05）。对于住院时间，根据研究对象的年龄不同，分为平均年龄≥60岁组和平均年龄<60岁组。平均年龄≥60岁组结果显示，与单纯的VSD治疗相比，ABC联合VSD治疗能缩短DFU患者的住院时间（MD=-6.82，95%CI=-10.93~-2.71，P=0.001）；平均年龄<60岁组结果显示，试验组和对照组比较，差异无统计学意义（MD=-5.11，95%CI=-17.78~7.56，P=0.45）。对于手术次数，根据创面处理的方式不同分为有植皮组和无植皮组。无植皮组的结果显示，与单纯的VSD治疗相比，ABC联合VSD治疗能减少DFU患者的手术次数（MD=-1.79，95%CI=-2.13~-1.46，P<0.05）；有植皮组的结果显示，与单纯的VSD治疗相比，ABC联合VSD治疗能明显减少DFU患者的手术次数（MD=-1.89，95%CI=-3.27~-0.50，P=0.008）。进行敏感性分析发现，本研究的结果稳健。

结论

ABC联合VSD是治疗DFU的安全高效疗法，尤其适用于非Wagner 5级患者及老年群体，联用抗生素及联合植皮术可进一步增效。

关键词: 糖尿病足, 足溃疡，糖尿病性, 骨水泥成形术, 抗生素骨水泥, 负压伤口疗法, 负压封闭引流, 创面愈合, Meta分析

CLC Number:

R 687.3　R 587.29

GUO Zhihong,CHEN Yingying,LIU Dewu. Efficacy and Safety of Antibiotic Bone Cement Combined with Vacuum Sealing Drainage for Diabetic Foot: a Meta-analysis[J]. Chinese General Practice, 2026, 29(30): 4503-4512. DOI: 10.12114/j.issn.1007-9572.2025.0102.
郭治宏,陈盈盈,刘德伍. 抗生素骨水泥联合负压封闭引流技术治疗糖尿病足有效性和安全性的Meta分析[J]. 中国全科医学, 2026, 29(30): 4503-4512. DOI: 10.12114/j.issn.1007-9572.2025.0102.

Figures/Tables 20

Figure 1 Flow chart of study selection

Table 1 Basic clinical characteristics of the included studies

序号	第一作者	年份（年）	入组患者数（例）		年龄（岁）		Wagner分级（级）	抗生素类别	创面处理方式	糖尿病足病程（d）		结局指标
序号	第一作者	年份（年）	试验组	对照组	试验组	对照组	Wagner分级（级）	抗生素类别	创面处理方式	试验组	对照组	结局指标
1	Yang^[11]	2024	40	20	57.1±8.4	56.5±7.7	3~4		更换敷料14 d，视情况缝合或皮瓣术	30	30	②⑥
2	Zhong^[14]	2024	12	16	58.83±10.72	67.11±9.25	3		7~9 d清创术	38	54.5	⑧
3	任红利^[19]	2023	20	20	52.60±4.38	51.40±4.99		万古霉素+庆大霉素	更换VSD/7 d，视情况植皮	39.80±21.96	37.70±21.21	①④⑧
4	郑泽文^[20]	2023	40	40	40.32±9.48	41.21±10.06		万古霉素	更换VSD/5~7 d	2 190±383	1 825±251	①②③④⑤
5	沈震晓^[16]	2022	20	20	53.14±5.40	53.10±5.45	2~4	万古霉素或妥布霉素	更换VSD/4~7d	>28	>28	③⑦⑨
6	刘爱蓬^[21]	2021	33	33	43~75	45~75		万古霉素	更换VSD/5~7 d	7~40	5~40	①⑦⑧
7	熊敏^[22]	2020	40	40	60.6±1.5	60.5±1.4		万古霉素	更换VSD/5~7 d			①②③⑤⑦
8	陈哲^[17]	2022	45	45	56.12±6.78	56.37±6.67	3~5	万古霉素	更换VSD/7 d，渗出多每4~5 d更换	303±70	312±76	①②④⑤⑦
9	杜元良^[23]	2018	53	48	59.2±9.5	59.2±9.5			更换VSD/7~9 d			①④⑤⑦
10	杨峰^[15]	2021	17	17	63.0±10.0	63.0±10.0	2~4		更换VSD/7 d，视情况植皮或皮瓣术			①④⑥
11	鲍晶晶^[18]	2022	32	32	64.04±4.82	64.04±4.31	4~5	万古霉素+庆大霉素	更换VSD/4~6 d，视情况植皮	30.13±5.87	29.56±6.08	①③④⑧
12	陶伟业^[12]	2022	40	40	59.07±10.46	58.15±9.39	3~4	万古霉素	更换VSD/5~7 d	23.41±6.78	29.56±6.08	①③④⑧
13	周敏^[13]	2022	40	40	60.84±1.35	60.92±1.27	3~4	万古霉素	VSD使用3 d后去除			①②③⑤

Figure 2 Risk of bias summary

Figure 3 Risk of bias graph

Figure 4 Forest plot of wound healing time between the test group and the control group for the treatment of diabetic foot

Figure 5 Forest plot of wound healing time for different wagner gradings

Figure 6 Sensitivity analysis of wound healing time in non-wagner grade 5

Figure 7 Forest plot of wound healing time for different types of antibiotics

Figure 8 Forest plot of clinical efficiency between the test group and the control group for the treatment of diabetic foot

Figure 9 Forest plot of number of bacterial to cloudy days between the test group and the control group for the treatment of diabetic foot

Figure 10 Sensitivity analysis of number of bacterial to cloudy days

Figure 11 Forest plot of duration of hospitalisation between the test group and the control group for the treatment of diabetic foot

Figure 12 Forest plot of duration of hospitalisation for different average ages

Figure 13 Forest plot of number of surgeries between the test group and the control group for the treatment of diabetic foot

Figure 14 Forest plot of number of surgeries with and without implant management

Figure 15 Forest plot of amputation rate between the test group and the control group for the treatment of diabetic foot

Figure 16 Forest plot of VAS score between the test group and the control group for the treatment of diabetic foot

Figure 17 Sensitivity analysis of VAS grades

Figure 18 Forest plot of bacterial positivity after 1 week between the test group and the control group for the treatment of diabetic foot

Figure 19 funnel chart of wound healing time

References 30

[1]	Zhao Y, Wang M, Meng B, et al. Identification of dysregulated complement activation pathways driven by N-glycosylation alterations in T2D patients[J]. Front Chem, 2021, 9: 677621. DOI: 10.3389/fchem.2021.677621.
[2]	Zawani M, Fauzi M B. Epigallocatechin gallate: the emerging wound healing potential of multifunctional biomaterials for future precision medicine treatment strategies[J]. Polymers (Basel), 2021, 13(21): 3656. DOI: 10.3390/polym13213656.
[3]	Du Y Q, Wang J, Fan W J, et al. Preclinical study of diabetic foot ulcers: from pathogenesis to vivo/vitro models and clinical therapeutic transformation[J]. Int Wound J, 2023, 20(10): 4394-4409. DOI: 10.1111/iwj.14311.
[4]	Dayya D, O'Neill O, Habib N, et al. Debridement of diabetic foot ulcers: public health and clinical implications - a systematic review, meta-analysis, and meta-regression[J]. BMJ Surg Interv Health Technol, 2022, 4(1): e000081. DOI: 10.1136/bmjsit-2021-000081.
[5]	Li F P, Mao Z Y, Du Y, et al. Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing[J]. J Nanobiotechnology, 2024, 22(1): 246. DOI: 10.1186/s12951-024-02423-6.
[6]	Klinder A, Zaatreh S, Ellenrieder M, et al. Antibiotics release from cement spacers used for two-stage treatment of implant-associated infections after total joint arthroplasty[J]. J Biomed Mater Res Part B Appl Biomater, 2019, 107(5): 1587-1597. DOI: 10.1002/jbm.b.34251.
[7]	Soleymani Eil Bakhtiari S, Bakhsheshi-Rad H R, Karbasi S, et al. Polymethyl methacrylate-based bone cements containing carbon nanotubes and graphene oxide: an overview of physical, mechanical, and biological properties[J]. Polymers (Basel), 2020, 12(7): 1469. DOI: 10.3390/polym12071469.
[8]	Phakatkar A H, Shirdar M R, Qi M L, et al. Novel PMMA bone cement nanocomposites containing magnesium phosphate nanosheets and hydroxyapatite nanofibers[J]. Mater Sci Eng C Mater Biol Appl, 2020, 109: 110497. DOI: 10.1016/j.msec.2019.110497.
[9]	Sangeetha R, Madheswari D, Priya G. Fabrication of poly (methyl methacrylate)/Ce/Cu substituted apatite/egg white (Ovalbumin)biocomposite owning adjustable properties: towards bone tissue rejuvenation[J]. J Photochem Photobiol B Biol, 2018, 187: 162-169. DOI: 10.1016/j.jphotobiol.2018.08.015.
[10]	陈家扬, 吴卓檀, 张卫华, 等. 超声清创联合负压封闭引流治疗糖尿病足溃疡的Meta分析与试验序贯分析[J]. 广西医学, 2024, 46(4): 556-565.
[11]	Yang C L, Wang D L. Antibiotic bone cement accelerates diabetic foot wound healing: elucidating the role of ROCK1 protein expression[J]. Int Wound J, 2024, 21(4): e14590. DOI: 10.1111/iwj.14590.
[12]	陶伟业, 蒋燕飞. 抗生素骨水泥治疗糖尿病足溃疡的临床价值[J]. 健康研究, 2022, 42(1): 114-117, 120. DOI: 10.19890/j.cnki.issn1674-6449.2022.01.026.
[13]	周敏, 薛国强, 张晓敏, 等. 载抗生素骨水泥治疗糖尿病足Wagner3、4级的疗效观察[J]. 中文科技期刊数据库(全文版)医药卫生, 2022(3): 29-31.
[14]	Zhong M F, Guo J W, Qahar M, et al. Combination therapy of negative pressure wound therapy and antibiotic-loaded bone cement for accelerating diabetic foot ulcer healing: a prospective randomised controlled trial[J]. Int Wound J, 2024, 21(10): e70089. DOI: 10.1111/iwj.70089.
[15]	杨峰, 李剑, 郝丽宏, 等. VSD序贯抗生素骨水泥间置治疗Wagner 2~4级糖尿病足的疗效分析[J]. 足踝外科电子杂志, 2021, 8(4): 56-60.
[16]	沈晓震, 郑艳峰, 陈宗相, 等. 抗生素骨水泥技术在Wanger2~4级糖尿病足治疗中的应用研究[J]. 河北医学, 2022, 28(3): 403-407.
[17]	陈哲, 何宗运. 抗生素骨水泥联合负压封闭吸引治疗糖尿病足的疗效分析[J]. 浙江创伤外科, 2022, 27(2): 249-251.
[18]	鲍晶晶, 黄显军, 姜磊. 抗生素骨水泥联合清创+负压封闭引流治疗糖尿病足溃疡创面的效果观察[J]. 中国基层医药, 2022, 29(7): 1031-1034. DOI: 10.3760/cma.j.cn341190-20200722-01268.
[19]	任红利. 抗生素骨水泥联合负压治疗糖尿病足溃疡的临床疗效观察[D]. 南充: 川北医学院, 2020. DOI: 10.27755/d.cnki.gcbyx.2020.000266.
[20]	郑泽文, 马世前. 抗生素骨水泥联合负压封闭吸引治疗糖尿病足的作用[J]. 特别健康, 2023(9): 239-240.
[21]	刘爱蓬, 刘衍松, 曹天勇. 糖尿病足溃疡创面修复中抗生素骨水泥的应用分析[J]. 糖尿病新世界, 2021, 24(2): 157-159. DOI: 10.16658/j.cnki.1672-4062.2021.02.157.
[22]	熊敏. VSD技术联合抗生素骨水泥在糖尿病足感染创面的应用[J]. 糖尿病新世界, 2020, 23(24): 176-178. DOI: 10.16658/j.cnki.1672-4062.2020.24.176.
[23]	杜元良, 肖天洁, 耿艳侠, 等. VSD技术联合抗生素骨水泥在糖尿病足感染创面的应用研究[J]. 糖尿病天地, 2018, 15(8): 142.
[24]	Liu L H, Liu D W. Bioengineered mesenchymal stem cell-derived exosomes: emerging strategies for diabetic wound healing[J]. Burns Trauma, 2024, 12: tkae030. DOI: 10.1093/burnst/tkae030.
[25]	Xu Y H, Xu X Y, Zhao Y, et al. A self-powered casein hydrogel E-dressing with synergistic photothermal therapy, electrical stimulation, and antibacterial effects for chronic wound management[J]. Acta Biomater, 2025, 198: 63-84. DOI: 10.1016/j.actbio.2025.03.047.
[26]	Xu Z B, Dai G G, Sun Z Y, et al. Application of antibiotic bone cement combined with lobulated perforator flap based on descending branch of the lateral circumflex femoral artery in treatment of infected traumatic tissue defects of foot[J]. BMC Musculoskelet Disord, 2024, 25(1): 673. DOI: 10.1186/s12891-024-07810-6.
[27]	Zhang Y L, Tian S W, Liu M Y, et al. Comparison of antibiotic-impregnated bone cement coverage versus vacuum sealing drainage in semi-open bone grafting using for tibial fracture with infected bone and soft tissue defect: a retrospective analysis[J]. BMC Musculoskelet Disord, 2023, 24(1): 401. DOI: 10.1186/s12891-023-06475-x.
[28]	谭斌, 王振林, 李登博, 等. 抗生素骨水泥封闭创面诱导膜植皮修复肌腱外露创面[J]. 中国骨伤, 2020, 33(6): 564-566. DOI: 10.12200/j.issn.1003-0034.2020.06.015.
[29]	Barakat N, Browne J A. Is bone cement implantation syndrome actually caused by cement a systematic review of the literature using the Bradford-hill criteria[J]. J Arthroplasty, 2025, 40(8S1): S353-S359. DOI: 10.1016/j.arth.2025.01.039.
[30]	Yang Y Z, Meng X Y, Huang Y R. Study of the cement implantation syndrome: a review[J]. Medicine (Baltimore), 2024, 103(24): e38624. DOI: 10.1097/MD.0000000000038624.