血小板裂解液与富血小板血浆治疗膝骨关节炎的临床研究

doi:10.3877/cma.j.issn.1674-134X.2020.05.008

目的

比较血小板裂解液(PL)与富血小板血浆(PRP)关节腔内注射治疗膝骨关节炎(KOA)的临床疗效。

方法

采用前瞻性随机对照研究的方法，选取2012年4月至2015年9月山东省文登整骨医院收治的150例KOA患者的150膝，通过随机数字表法分为血小板裂解液(PL)组、富血小板血浆(PRP)组和玻璃酸钠(HA)组(每组50例)，3组关节腔注射PL、PRP和HA频次为每周1次，连续5周。选择治疗前、治疗后1、3、6个月为时间观察点，西安大略和麦克马斯特大学(WOMAC)疼痛评分、Lequesne肿胀评分及WOMAC综合评分评价治疗前后关节疼痛、肿胀情况及综合功能等方面的区别，同时记录3组病例在治疗过程中不良反应发生情况并进行比较。Fisher精确检验、方差分析或t检验用于数据分析比较。

结果

PL组49例，PRP组48例，HA组47例成功完成治疗及6个月以上随访。3组患者在治疗后1个月时WOMAC疼痛评分最低；治疗后3及6个月比较，PL组与PRP组低于HA组(3个月：t＝1.115，P<0.01；t＝2.343，P<0.05；6个月：t＝0.463，P<0.05；t＝1.983，P<0.01)，PL组与PRP组比较，差异无统计学意义(t＝3.123、2.983，均为P>0.05)。Lequesne肿胀评分在治疗后3个月时PL组低于PRP组与HA组(t＝3.132，P<0.05；t＝1.545，P<0.01)，PRP组低于HA组(t＝2.654，P<0.05)。治疗后6个月时，PL组与PRP组均低于HA组(t＝2.513，P<0.05；t＝3.313，P<0.01)，PL组与PRP组比较差异无统计学意义(t＝2.343，P>0.05)。3组治疗完成后WOMAC综合评分比较：治疗后3个月PL组低于PRP组与HA组(t＝2.442，P<0.05；t＝2.415，P<0.01)，PRP组低于HA组(t＝1.324，P<0.01)；治疗6个月比较，PL组与PRP组低于HA组(t＝1.613，P<0.05；t＝2.913，P<0.01)，PL组与PRP组比较差异无统计学意义(t＝3.413，P>0.05)。不良反应发生率的比较中，PL组不良反应发生率(2.0%)低于HA组(8.5%)(P<0.05)；PL组低于PRP组(P>0.05)，PRP组低于HA组(P>0.05)，但差异均无统计学意义。

结论

血小板裂解液治疗膝骨关节炎能够取得与富血小板血浆同样的治疗效果，均优于玻璃酸钠，同时不良反应发生率低。

关键词: 骨关节炎, 富血小板血浆, 透明质酸

Objective

To compare the clinical outcomes in the treatment of osteoarthritis (OA) of the knee with platelet lysate (PL) versus platelet-rich plasma (PRP) or hyaluronic acid(HA).

Methods

This prospective randomized controlled clinical trial involved 150 patientsadmitted in Wendeng orthopaedic hospital of Shandong province from April 2012to September 2015. The patients were randomly divided into three groups: PL group, PRP group and HA group (50 cases in each). The frequency of PL, PRP and HA injection was three times a week and for five weeks. The Western Ontario McMaster University (WOMAC) pain score, Lequesne swelling score and WOMAC osteoarthritis index were used to evaluate the joint pain, swelling and comprehensive function of patients among three groups before and one, three, and six months after treatment. The incidence of adverse events was record and compared among the three groups. Fisher exact test, variance analysis or t test were performed for data comparison.

Results

At the six month follow-up, 49 cases of PL group, 48 cases of PRP group and 47 cases of HA group successfully completed treatment. Three groups had the lowest WOMAC pain score at one months after treatment. Compared with the HA group, the WOMAC pain scores of the PL group and the PRP group were lower than those in the HA group (three months: t=1.115, P<0.01, t=2.343, P<0.05; six months: t=0.463, P<0.05, t=1.983, P<0.01)at three and six months after treatment. There was no significant difference of WOMAC pain scores between PL group and PRP group (t=3.123, 2.983, both P>0.05). Lequesne swelling score in PL group was lower than those in PRP group and HA group at three months after treatment, and the difference was statistically significant(t=3.132, P<0.05, t=1.545, P<0.01). Compared with the HA group, the Lequesne swelling scores of PL group and the PRP group were lower (t=2.513, P<0.05, t=3.313, P<0.01)at six months after treatment. However, there was no significant difference between PL group and PRP group (t=2.343, P>0.05). The WOMAC score of the PL groups was lower than those of the PRP group and the HA group at three months after treatment, and the difference was statistically significant (t=2.442, P<0.05, t=2.415, P<0.01). In the meantime, the WOMAC score of the PRP groups was lower than that of the HA group(t=1.324, P<0.01). Compared with the HA group, the WOMAC scores of PL group and the PRP group were lower than those in the HA group (t=1.613, 2.913, both P<0.01)at sixmonths after treatment. However, there was no significant difference between PL group and PRP group (t=3.413, P>0.05). In the comparison of the total incidence of adverse reactions, the incidence of adverse reactions in PL group(2.0%) was lower than that of HA group (8.5%), and the difference was statistically significant (P<0.05). The incidence of adverse reactions in PL group was lower than that of PRP group (P >0.05), and the incidence of adverse reactions in PRP group was lower than that of the HA group (P>0.05), but the difference was not statistically significant.

Conclusion

Compared with PRP, PL in the treatment of knee osteoarthritis could achieve the same effect, and both of them are superior to HA, meanwhile, the incidence of adverse reactions of PL is lower.

Key words: Osteoarthritis, Platelet-rich plasma, Hyaluronic acid

表1 各组KOA患者基线资料比较

组别	例数	性别		年龄[岁，(±s)]	BMI[kg/m²，(±s) ]	K-L分级(例)			病程[月，(±s)]
组别	例数	男	女	年龄[岁，(±s)]	BMI[kg/m²，(±s) ]	Ⅰ	Ⅱ	Ⅲ	病程[月，(±s)]
PL组	49	21	28	58±7	25± 4	5	35	9	41±20
PRP组	48	22	26	58±7	25± 3	5	36	7	40±18
HA组	47	22	25	58±7	25± 4	6	33	9	35±20
统计值		F＝0.033		t＝0.064	t＝0.242	χ²＝0.323			F＝1.361
P值		>0.05		>0.05	>0.05	>0.05			>0.05

表1 各组KOA患者基线资料比较

组别	例数	性别		年龄[岁，(±s)]	BMI[kg/m²，(±s) ]	K-L分级(例)			病程[月，(±s)]
组别	例数	男	女	年龄[岁，(±s)]	BMI[kg/m²，(±s) ]	Ⅰ	Ⅱ	Ⅲ	病程[月，(±s)]
PL组	49	21	28	58±7	25± 4	5	35	9	41±20
PRP组	48	22	26	58±7	25± 3	5	36	7	40±18
HA组	47	22	25	58±7	25± 4	6	33	9	35±20
统计值		F＝0.033		t＝0.064	t＝0.242	χ²＝0.323			F＝1.361
P值		>0.05		>0.05	>0.05	>0.05			>0.05

表2 各组治疗前后各观察点WOMAC疼痛评分比较[分，(±s)]

组别	例数	治疗前	治疗后1个月	治疗后3个月	治疗后6个月	F值	P值
PL组	49	9.5±0.7^e	4.3±0.5^ef	4.5±0.6^aef	5.6±0.8^ecf	658.893	<0.001
PRP组	48	9.7±0.7^g	4.5±0.7^gh	4.6±0.9^bgh	5.6±1.1^dgh	393.721	<0.001
HA组	47	9.5±0.8ⁱ	4.4±0.8^ij	5.3±1.1^abijk	6.4±1.2^cdjk	234.626	<0.001
F值		1.007	0.631	12.402	10.401
P值		>0.05	>0.05	<0.001	<0.001

表2 各组治疗前后各观察点WOMAC疼痛评分比较[分，(±s)]

组别	例数	治疗前	治疗后1个月	治疗后3个月	治疗后6个月	F值	P值
PL组	49	9.5±0.7^e	4.3±0.5^ef	4.5±0.6^aef	5.6±0.8^ecf	658.893	<0.001
PRP组	48	9.7±0.7^g	4.5±0.7^gh	4.6±0.9^bgh	5.6±1.1^dgh	393.721	<0.001
HA组	47	9.5±0.8ⁱ	4.4±0.8^ij	5.3±1.1^abijk	6.4±1.2^cdjk	234.626	<0.001
F值		1.007	0.631	12.402	10.401
P值		>0.05	>0.05	<0.001	<0.001

表3 各组治疗前后各观察点肿胀情况比较[分，(±s)]

组别	例数	治疗前	治疗后1个月	治疗后3个月	治疗后6个月	F值	P值
PL组	49	1.98±0.61^d	0.73±0.55^de	0.43±0.29^abde	0.66±0.32^cde	85.656	<0.001
PRP组	48	1.84±0.66^f	0.75±0.58^f	0.75±0.37^abf	0.71±0.46^cf	54.214	<0.001
HA组	47	1.91±0.65^g	0.83±0.56^ghi	1.08±0.70^bghi	1.20±0.63^cgi	22.862	<0.001
F值		0.004	0.391	21.646	18.022
P值		>0.05	>0.05	<0.001	<0.001

表3 各组治疗前后各观察点肿胀情况比较[分，(±s)]

组别	例数	治疗前	治疗后1个月	治疗后3个月	治疗后6个月	F值	P值
PL组	49	1.98±0.61^d	0.73±0.55^de	0.43±0.29^abde	0.66±0.32^cde	85.656	<0.001
PRP组	48	1.84±0.66^f	0.75±0.58^f	0.75±0.37^abf	0.71±0.46^cf	54.214	<0.001
HA组	47	1.91±0.65^g	0.83±0.56^ghi	1.08±0.70^bghi	1.20±0.63^cgi	22.862	<0.001
F值		0.004	0.391	21.646	18.022
P值		>0.05	>0.05	<0.001	<0.001

表4 各组治疗前后各时间观察点WOMAC评分比较[分，(±s)]

组别	例数	治疗前	治疗后1个月	治疗后3个月	治疗后6个月	F值	P值
PL组	49	54±10^e	28±7^ef	23±6^abef	26±6^def	175.395	<0.001
PRP组	48	53±10^g	31±9^gh	26±7^acgh	28±8^dgh	88.042	<0.001
HA组	47	54±10ⁱ	30±9ⁱ	30±8^bci	33±7^d	82.192	<0.001
F值		0.056	0.696	15.468	17.579
P值		>0.05	>0.05	<0.001	<0.001

表4 各组治疗前后各时间观察点WOMAC评分比较[分，(±s)]

组别	例数	治疗前	治疗后1个月	治疗后3个月	治疗后6个月	F值	P值
PL组	49	54±10^e	28±7^ef	23±6^abef	26±6^def	175.395	<0.001
PRP组	48	53±10^g	31±9^gh	26±7^acgh	28±8^dgh	88.042	<0.001
HA组	47	54±10ⁱ	30±9ⁱ	30±8^bci	33±7^d	82.192	<0.001
F值		0.056	0.696	15.468	17.579
P值		>0.05	>0.05	<0.001	<0.001

表5 各组患者注射后的不良反应情况

组别	例数	不良反应例数(例)	发生率(%)
HA	47	4	8.5^*
PRP	48	2	4.2
PL	49	1	2.0^*
总计	144	7	4.9
P值			0.037

表5 各组患者注射后的不良反应情况

组别	例数	不良反应例数(例)	发生率(%)
HA	47	4	8.5^*
PRP	48	2	4.2
PL	49	1	2.0^*
总计	144	7	4.9
P值			0.037

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Comparative study of platelet lysate and platelet-rich plasma in treatment of knee osteoarthritis

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Comparative study of platelet lysate and platelet-rich plasma in treatment of knee osteoarthritis