Effect of anti-resorptive agents affect on bone repair. A meta-analysis of randomized controlled studies

doi:10.3877/cma.j.issn.2096-0263.2022.01.007

Abstract

Abstract:

Objective

The meta-analysis was performed to determine whether the early use of the anti-resorptive drugs would affect bone union.

Methods

We searched MEDLINE, EMBASE, CENTRAL and CBM for the related studies from each database inception until December 19, 2020. The inclusion criteria were all relevant clinical randomized controlled studies that studied the relationship between the anti-resorptive drugs and bone union. We assessed the quality of the included studies with version 5.2 of the Cochrane risk-of-bias tool, and the software for data synthesis was Review Manager 5.4.1. The effect measure was risk ratio (RR) with 95% confidence interval (CI), the Mantel-Haenszel method and the fixed effect model were used to analyze data.

Results

25 studies met the inclusion criteria, 18 studies were included in the meta-analysis, including 3, 421 people, the total bone union RR=1.013(95% CI: 0.994, 1.032, P=0.198). In the sensitivity analysis of excluding 11 non-low-risk studies, RR=1.008 (95% CI: 0.987, 1.029, P=0.475). In the subgroup analysis, the limb fracture population(9 studies, 2, 891 persons), RR= 1.009 (95% CI: 0.989, 1.029, P=0.399); the spinal fusion population (9 studies, 530 persons), RR=1.034 (95% CI: 0.979, 1.091, P=0.230), the osteoporotic population (13 studies, 749 persons), RR=1.038 (95% CI: 0.993, 1.086, P=0.103); the internal fixation surgery population (15 studies, 2,967 persons), RR=1.005 (95% CI: 0.989, 1.021, P=0.540). The results of each analysis included an invalid value of 1, that is, the early use of the anti-resorptive drugs in bone repair did not affect bone union.

Conclusions

In general, the early application of the anti-resorptive drugs in bone repair does not affect bone union. Among them, no matter the limb fracture patients or the spinal fusion patients, whether the osteoporotic patients, or the patients undergoing internal fixation surgery, the use of the anti-resorptive drugs in the early stage of bone repair to prevent secondary osteoporosis fracture does not affect bone union. Therefore, for patients suitable for anti-osteoporosis treatment, it is recommended to start anti-osteoporosis treatment immediately after fracture.

Key words: The anti-resorptive drugs, Bone union, Spinal fusion, Fracture healing, Meta-analysis

Hairui Fu, Luyang Yang, Bin Liang, Qiang Liu. Effect of anti-resorptive agents affect on bone repair. A meta-analysis of randomized controlled studies[J]. Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition), 2022, 08(01): 35-43.

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Figures/Tables 3

References 56

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研究编码	国家	OP	骨折部位	手术/方法	实验组（人）	对照组（人）	干预	对照
高勇2017^[37]	中国	是	转子间	ORIF/PFNA	15	15	ALN	空白
Colón-Emeric 2011^[33]	美国	否	髋部	手术方法由治疗医生决定	1 065	1 062	ZOL	安慰剂
Duckworth 2019^[30]	英国	否	桡骨远端	由经治医生决定手术或保守	196	183	ALN	安慰剂
Gong 2012^[36]	韩国	是	桡骨远端	ORIF/掌侧板	24	26	ALN	ALN（术后3月执行）
Harding 2011^[32]	瑞典	否	胫骨平台近端截骨	HCO/外固定架	25	21	ZOL	安慰剂
Kim 2012^[35]	韩国	是	转子间	加压螺钉或髓内钉（由术者决定）	47	24	RIS	RIS（术后3月执行）
Nagahama 2011^[34]	日本	是	腰椎融合	PLIF/双Cage+椎间隙植骨/自体骨和磷酸三钙	19	17	ALN	维生素D
van der Poest 2000^[46]	荷兰	是	桡骨远端	否	18	19	ALN	安慰剂
van der Poest 2002^[31]	荷兰	否	下肢	由经治医生决定手术或保守	20	18	ALN	安慰剂
研究编码	干预执行时间	干预持续时间（月）	评估时间	实验组骨连接（人）	对照组骨连接（人）
高勇2017^[37]	10~14天	12	3月	10	9
Colón-Emeric 2011^[33]	90天内	36	至少6周	1031	1033
Duckworth 2019^[30]	14天内	6	8周	121	103
Gong 2012^[36]	14天	-	10周	24	26
Harding 2011^[32]	4周	12	12周	24	20
Kim 2012^[35]	1周或1月	12	12周	35	15
Nagahama 2011^[34]	1周	12	12月	18	11
van der Poest 2000^[46]	平均4~5周	12	-	18	18
van der Poest 2002^[31]	2周	12	-	19	17
Yang 2018^[38]	中国	是	拇外翻行近节趾骨截骨、跖跗关节融合	螺钉固定	56	57	ZOL
陈莹2019^[43]	中国	是	腰椎融合	PLIF/Cage/自体骨	31	32人	ZOL
李辉南2016^[41]	中国	是	腰椎融合	PLIF/自体骨	20	18	ZOL
刘汉辉2019^[44]	中国	是	腰椎融合	TLIF	32	30	ZOL
潘晟2014^[40]	中国	是	腰椎融合	PLIF	40	40	ZOL
尹自龙2020^[45]	中国	是	颈椎融合	前路/异体骨	28	29	ZOL
Chen 2016^[27]	中国	是	腰椎融合	PLIF/自体骨+异体骨	33	36	ZOL
Li 2012^[39]	中国	否	腰椎融合	TLIF/Cage/自体骨	41人	41人	ZOL
Liu 2019^[42]	中国	是	颈椎融合	ACDF/Cage/异体骨	21	22	ZOL
Yang 2018^[38]	安慰剂	1周	6	12周	56	57
陈莹2019^[43]	空白	1周	12	-	27*	28*
李辉南2016^[41]	空白	1~2周	12	-	20	16
刘汉辉2019^[44]	空白	第5天	12	12月	29	28
潘晟2014^[40]	空白	第7天	12	-	40	39
尹自龙2020^[45]	安慰剂	第2~3天	12	12月	28	29
Chen 2016^[27]	安慰剂	3天	12	12月	27	30
Li 2012^[39]	安慰剂	3天	12	12月	36	35
Liu 2019^[42]	安慰剂	第5天	12	12月	21	22

研究编码	国家	OP	骨折部位	手术/方法	实验组（人）	对照组（人）	干预	对照
高勇2017^[37]	中国	是	转子间	ORIF/PFNA	15	15	ALN	空白
Colón-Emeric 2011^[33]	美国	否	髋部	手术方法由治疗医生决定	1 065	1 062	ZOL	安慰剂
Duckworth 2019^[30]	英国	否	桡骨远端	由经治医生决定手术或保守	196	183	ALN	安慰剂
Gong 2012^[36]	韩国	是	桡骨远端	ORIF/掌侧板	24	26	ALN	ALN（术后3月执行）
Harding 2011^[32]	瑞典	否	胫骨平台近端截骨	HCO/外固定架	25	21	ZOL	安慰剂
Kim 2012^[35]	韩国	是	转子间	加压螺钉或髓内钉（由术者决定）	47	24	RIS	RIS（术后3月执行）
Nagahama 2011^[34]	日本	是	腰椎融合	PLIF/双Cage+椎间隙植骨/自体骨和磷酸三钙	19	17	ALN	维生素D
van der Poest 2000^[46]	荷兰	是	桡骨远端	否	18	19	ALN	安慰剂
van der Poest 2002^[31]	荷兰	否	下肢	由经治医生决定手术或保守	20	18	ALN	安慰剂
研究编码	干预执行时间	干预持续时间（月）	评估时间	实验组骨连接（人）	对照组骨连接（人）
高勇2017^[37]	10~14天	12	3月	10	9
Colón-Emeric 2011^[33]	90天内	36	至少6周	1031	1033
Duckworth 2019^[30]	14天内	6	8周	121	103
Gong 2012^[36]	14天	-	10周	24	26
Harding 2011^[32]	4周	12	12周	24	20
Kim 2012^[35]	1周或1月	12	12周	35	15
Nagahama 2011^[34]	1周	12	12月	18	11
van der Poest 2000^[46]	平均4~5周	12	-	18	18
van der Poest 2002^[31]	2周	12	-	19	17
Yang 2018^[38]	中国	是	拇外翻行近节趾骨截骨、跖跗关节融合	螺钉固定	56	57	ZOL
陈莹2019^[43]	中国	是	腰椎融合	PLIF/Cage/自体骨	31	32人	ZOL
李辉南2016^[41]	中国	是	腰椎融合	PLIF/自体骨	20	18	ZOL
刘汉辉2019^[44]	中国	是	腰椎融合	TLIF	32	30	ZOL
潘晟2014^[40]	中国	是	腰椎融合	PLIF	40	40	ZOL
尹自龙2020^[45]	中国	是	颈椎融合	前路/异体骨	28	29	ZOL
Chen 2016^[27]	中国	是	腰椎融合	PLIF/自体骨+异体骨	33	36	ZOL
Li 2012^[39]	中国	否	腰椎融合	TLIF/Cage/自体骨	41人	41人	ZOL
Liu 2019^[42]	中国	是	颈椎融合	ACDF/Cage/异体骨	21	22	ZOL
Yang 2018^[38]	安慰剂	1周	6	12周	56	57
陈莹2019^[43]	空白	1周	12	-	27*	28*
李辉南2016^[41]	空白	1~2周	12	-	20	16
刘汉辉2019^[44]	空白	第5天	12	12月	29	28
潘晟2014^[40]	空白	第7天	12	-	40	39
尹自龙2020^[45]	安慰剂	第2~3天	12	12月	28	29
Chen 2016^[27]	安慰剂	3天	12	12月	27	30
Li 2012^[39]	安慰剂	3天	12	12月	36	35
Liu 2019^[42]	安慰剂	第5天	12	12月	21	22

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