Association of Degenerative Knee Osteoarthritis Pain with Sex Hormone and Inflammatory Cytokines in Synovial Fluids in Postmenopausal Women

doi:10.12114/j.issn.1007-9572.2022.0335

Chinese General Practice ›› 2022, Vol. 25 ›› Issue (29): 3652-3657.DOI: 10.12114/j.issn.1007-9572.2022.0335

Special Issue: 骨健康最新文章合辑；女性健康最新文章合辑

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Association of Degenerative Knee Osteoarthritis Pain with Sex Hormone and Inflammatory Cytokines in Synovial Fluids in Postmenopausal Women

1. Department of Traumatic Orthopedics, the Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
2. Department of Gastroenterology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China

Received:2022-02-10 Revised:2022-05-15 Published:2022-10-15 Online:2022-06-30
Contact: Jian RAN
About author:
MOU L M, ZHANG W H, ZHANG S P, et al. Association of degenerative knee osteoarthritis pain with sex hormone and inflammatory cytokines in synovial fluids in postmenopausal women[J]. Chinese General Practice, 2022, 25 (29) : 3652-3657. Note: MOU Limin and ZHANG Wenhao are co-first authors

绝经后女性退变性膝骨关节炎疼痛与性激素水平及关节液炎性因子的相关性研究

1．830000　新疆维吾尔自治区乌鲁木齐市，新疆医科大学第六附属医院创伤骨科
2．830000　新疆维吾尔自治区乌鲁木齐市，新疆医科大学第一附属医院消化内科

通讯作者: 冉建
作者简介:
注：牟利民和张文豪为共同第一作者牟利民，张文豪，张思平，等.绝经后女性退变性膝骨关节炎疼痛与性激素水平及关节液炎性因子的相关性研究[J].中国全科医学，2022，25（29）：3652-3657.[www.chinagp.net] 作者贡献：牟利民进行文章的构思与设计，文献整理与分析，文章撰写和修订；张文豪、张思平、覃祺、韩明展负责研究的实施和数据收集与整理；陈万吉、冉建负责文章的质量控制及审校；冉建对文章整体负责，监督管理。
基金资助:
新疆维吾尔自治区自然科学基金资助项目(2019D01C244)

Abstract

Abstract:

Background

The pain induced by degenerative knee osteoarthritis (KOA) is common in postmenopausal women, but there is a lack of clinical evidence on whether it has an association with decreased sex hormone levels and inflammatory cytokines in the synovial fluid.

Objective

To assess the associations of degenerative KOA pain with sex hormones in the serum 〔estradiol (E₂) , testosterone (T) , prolactin, luteinizing hormone (LH) , follicle-stimulating hormone (FSH) and progesterone (P) 〕, and inflammatory cytokines in synovial fluids 〔interleukin-1 (IL-1) , IL-6, IL-10 and tumor necrosis factor-α (TNF-α) 〕 in postmenopausal women, providing a novel basis for estrogen hormone treatment of pain induced by degenerative KOA.

Methods

Ninety postmenopausal women with pain induced by degenerative KOA were recruited from the Sixth Affiliated Hospital of Xinjiang Medical University from June 2019 to June 2021, including 30 with mild pain (VAS score ≤ 3) , 30 with moderate pain (VAS score higher than 4 but lower than 7) , and 30 with severe pain (VAS score higher than 7 but lower than 10) . They were compared to 30 postmenopausal women with knee effusion (controls) undergoing physical examination in the hospital during the same period. The levels of serum sex hormones and inflammatory cytokines in synovial fluids were measured in all cases. All subjects were tested for sex hormones in the serum and inflammatory cytokines in synovial fluids.

Results

The BMI differed across mild, moderate, and severe pain subgroups and the controls (P<0.05) . In particular, severe pain subgroup had higher BMI than did controls and mild pain subgroup (P<0.05) . The serum levels of E₂ and T differed across mild, moderate, and severe pain subgroups and the controls (P<0.05) . Specifically, the controls had higher levels of E₂ and T than did moderate and severe pain subgroups (P<0.05) . The E₂ level in the moderate pain subgroup was lower than that of mild pain subgroup (P<0.05) . The E₂ and T levels in the severe pain subgroup were lower than those in the mild pain subgroup (P<0.05) . There were no significant differences in prolactin, LH, FSH and P between controls, and mild, moderate and severe pain subgroups (P>0.05) . The levels of IL-1, IL-6, and IL-10 as well as TNF-α varied across mild, moderate, and severe pain subgroups and the controls (P<0.05) . Compared with controls, mild pain subgroup had higher IL-1 level, and moderate and severe pain subgroups had higher IL-1, IL-6, IL-10 and TNF-α levels (P<0.05) . The levels of IL-6, IL-10 and TNF-α in severe pain subgroup were higher than those in mild pain subgroup (P<0.05) . E₂ and T levels were negatively correlated with VAS score for degenerative knee pain (r_s=-0.686, -0.454, P<0.05) ; IL-1, IL-6 and TNF-α levels were positively correlated with VAS score for degenerative knee pain (r_s=0.517, 0.665, 0.319, P<0.05) . There was no correlation between IL-10 and VAS score for degenerative knee pain (r_s=0.162, P>0.05) .

Conclusion

In postmenopausal women, VAS score for degenerative knee pain was negatively correlated with E₂ and T levels. There was no significant difference in prolactin, LH, FSH and P levels among degenerative KOA patients with different pain levels. The IL-1, IL-6 and TNF-α levels in synovial fluids were positively correlated with the VAS score of degenerative knee pain. So reducing the levels of IL-1, IL-6 and TNF-α could improve the tolerance of knee pain, which may be a reference for clinical treatment of degenerative knee pain.

Key words: Sex hormones, Synovia, Postmenopause, Inflammatory factors, Knee pain, Osteoarthritis, knee

摘要：

背景

绝经后女性退变性膝骨关节炎（KOA）疼痛患者较为多见。绝经后女性体内性激素水平降低，体内性激素水平及关节液中炎性因子是否会影响膝关节疼痛，目前缺乏临床实践证据。

目的

探讨绝经后退变性KOA疼痛与患者血液中性激素〔雌二醇（E₂）、睾酮（T）、泌乳素（PRL）、促黄体生成素（LH）、卵泡刺激素（FSH）及孕酮（P）〕水平、膝关节液炎性因子〔白介素（IL）-1、IL-6、IL-10及肿瘤坏死因子α（TNF-α）〕之间的相关性，为临床中雌激素治疗退变性KOA疼痛提供新的诊疗依据。

方法

选取新疆医科大学第六附属医院2019年6月至2021年6月因退变性KOA疼痛住院的女性绝经患者90例，患者行视觉模拟量表（VAS）评分后分为轻度疼痛组30例（VAS评分≤3分）、中度疼痛组30例（VAS评分4~6分）及重度疼痛组30例（VAS评分7~10分）；对照组选取新疆医科大学第六附属医院同期体检的绝经后膝关节积液女性30例。所有受试者检测性激素和膝关节液中炎性因子。

结果

四组患者体质指数（BMI）比较，差异有统计学意义（P<0.05），其中对照组、轻度疼痛组BMI低于重度疼痛组（P<0.05）。四组患者的E₂及T比较，差异有统计学意义（P<0.05），其中中、重度疼痛组E₂、T均低于对照组，中、重度疼痛组E₂与重度疼痛组T均低于轻度疼痛组（P<0.05）。对照组及轻、中、重度疼痛组退变性KOA患者的PRL、LH、FSH及P比较，差异均无统计学意义（P>0.05）。四组患者IL-1、IL-6、IL-10及TNF-α水平比较，差异均有统计学意义（P<0.05），其中轻度疼痛组IL-1，中、重度疼痛组IL-1、IL-6、IL-10、TNF-α均高于对照组，重度疼痛组IL-6、IL-10、TNF-α均高于轻度疼痛组（P<0.05）。E₂和T与膝关节疼痛VAS评分呈负相关（r_s=-0.686、-0.454，P<0.05），IL-1、IL-6及TNF-α与膝关节疼痛VAS评分呈正相关（r_s=0.517、0.665、0.319，P<0.05），IL-10与膝关节疼痛VAS评分之间无相关关系（r_s=0.162，P>0.05）。

结论

绝经后退变性KOA疼痛患者体内E₂及T水平与VAS评分呈负相关，不同疼痛程度退变性KOA患者的PRL、LH、FSH及P水平之间无明显差异。绝经后退变性KOA患者膝关节液中IL-1、IL-6及TNF-α水平与VAS评分呈正相关，降低关节内IL-1、IL-6及TNF-α水平可提高机体对膝关节疼痛的耐受，为临床上治疗退变性膝关节疼痛提供了一定的参考依据。

关键词: 性激素, 绝经后期, 关节液, 炎性因子, 膝关节疼痛, 骨关节炎，膝

Limin MOU,Wenhao ZHANG,Siping ZHANG, et al. Association of Degenerative Knee Osteoarthritis Pain with Sex Hormone and Inflammatory Cytokines in Synovial Fluids in Postmenopausal Women[J]. Chinese General Practice, 2022, 25(29): 3652-3657. DOI: 10.12114/j.issn.1007-9572.2022.0335.
牟利民,张文豪,张思平等. 绝经后女性退变性膝骨关节炎疼痛与性激素水平及关节液炎性因子的相关性研究[J]. 中国全科医学, 2022, 25(29): 3652-3657. DOI: 10.12114/j.issn.1007-9572.2022.0335.

Figures/Tables 4

References 26

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组别	例数	病程（年）	年龄（岁）	绝经年龄（岁）	BMI （kg/m²）
对照组	30	—	56.8±5.1	50.5±4.0	25.4±1.1
轻度疼痛组	30	3.2±0.9	57.9±5.2	50.5±3.8	25.6±1.0
中度疼痛组	30	3.7±1.1	57.2±4.9	50.1±3.7	25.8±1.0
重度疼痛组	30	3.8±1.2	57.9±4.0	50.5±3.6	26.2±1.0^ab
F值		2.827	0.350	0.129	2.714
P值		0.065	0.789	0.943	0.048

组别	例数	病程（年）	年龄（岁）	绝经年龄（岁）	BMI （kg/m²）
对照组	30	—	56.8±5.1	50.5±4.0	25.4±1.1
轻度疼痛组	30	3.2±0.9	57.9±5.2	50.5±3.8	25.6±1.0
中度疼痛组	30	3.7±1.1	57.2±4.9	50.1±3.7	25.8±1.0
重度疼痛组	30	3.8±1.2	57.9±4.0	50.5±3.6	26.2±1.0^ab
F值		2.827	0.350	0.129	2.714
P值		0.065	0.789	0.943	0.048

组别	例数	E₂（ng/L）	T（μg/L）	PRL（μg/L）	LH（U/L）	FSH（U/L）	P（μg/L）
对照组	30	63.99±22.84	0.73±0.39	16.55±4.08	21.49±10.09	31.61±13.06	1.27±1.06
轻度疼痛组	30	63.50±22.66	0.65±0.40	16.07±5.69	23.35±11.18	32.21±13.65	1.18±1.01
中度疼痛组	30	46.49±22.97^ab	0.55±0.39^a	14.89±5.64	24.19±11.86	34.43±12.95	1.09±0.99
重度疼痛组	30	39.98±24.05^ab	0.43±0.36^ab	13.75±5.44	25.33±12.92	37.15±13.47	1.09±0.93
F值		8.251	3.223	1.674	0.587	1.073	0.152
P值		<0.001	0.025	0.176	0.625	0.363	0.928

组别	例数	E₂（ng/L）	T（μg/L）	PRL（μg/L）	LH（U/L）	FSH（U/L）	P（μg/L）
对照组	30	63.99±22.84	0.73±0.39	16.55±4.08	21.49±10.09	31.61±13.06	1.27±1.06
轻度疼痛组	30	63.50±22.66	0.65±0.40	16.07±5.69	23.35±11.18	32.21±13.65	1.18±1.01
中度疼痛组	30	46.49±22.97^ab	0.55±0.39^a	14.89±5.64	24.19±11.86	34.43±12.95	1.09±0.99
重度疼痛组	30	39.98±24.05^ab	0.43±0.36^ab	13.75±5.44	25.33±12.92	37.15±13.47	1.09±0.93
F值		8.251	3.223	1.674	0.587	1.073	0.152
P值		<0.001	0.025	0.176	0.625	0.363	0.928

组别	例数	IL-1	IL-6	IL-10	TNF-α
对照组	30	6.13（2.33）	1.97（0.69）	49.21（45.05）	6.09（2.99）
轻度疼痛组	30	10.74（4.07）^a	3.53（1.45）^a	78.00（71.57）	7.51（3.49）
中度疼痛组	30	13.22（4.45）^a	5.42（1.74）^a	100.04（67.32）^a	8.24（4.49）^a
重度疼痛组	30	15.56（4.23）^a	7.47（2.21）^ab	120.72（72.37）^ab	11.59（5.15）^ab
Z值		69.93	81.97	26.10	46.74
P值		<0.001	<0.001	<0.001	<0.001

Association of Degenerative Knee Osteoarthritis Pain with Sex Hormone and Inflammatory Cytokines in Synovial Fluids in Postmenopausal Women

绝经后女性退变性膝骨关节炎疼痛与性激素水平及关节液炎性因子的相关性研究

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指标	r_s值	P值
E₂	-0.686	<0.001
T	-0.454	<0.001
IL-1	0.517	<0.001
IL-6	0.665	<0.001
IL-10	0.162	0.128
TNF-α	0.319	0.002

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