早期膝骨关节炎患者血清雌二醇和睾酮水平与病变程度的关系
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摘要
背景:研究表明膝关节骨关节炎绝经后女性的患病率更明显高于同龄段男性,根据膝关节骨关节炎特殊的发病年龄和性别提示性激素水平与膝关节骨关节炎的发病机制可能有密切相关性。目的:在早期的膝关节骨关节炎患者中,探索绝经后女性和同龄男性的血清中性激素水平与膝关节骨关节炎严重程度的相关性。方法:采集膝关节骨关节炎患者44例和正常人29例,共73例,按性别差异分为绝经后女性组(n=37)和对应年龄段男性组(n=36),两组再参照Kellgren-Lawrence(K-L)分级标准,分为K-L0级、Ⅰ级、Ⅱ级3个亚组。采用电化学发光法检测各组血清中的雌二醇和睾酮水平,分别关联受试者的K-L分级,分析其与K-L分级的相关性。结果与结论:(1)在绝经后女性膝关节骨关节炎患者中,K-L分级0级与Ⅰ级者血清中雌二醇的水平差异无显著性意义(P> 0.05),0级、Ⅰ级分别与Ⅱ级的血清中雌二醇水平差异有显著意义(P <0.05);(2)绝经后女性膝关节骨关节炎按K-L分级0级、Ⅰ级、Ⅱ级的血清中睾酮水平两两比较差异均无显著性意义(P> 0.05);(3)绝经后女性膝关节骨关节炎严重程度与血清雌二醇水平呈现出明显的负相关性(r_s=-0.709, P <0.05),与血清睾酮水平无明显相关性(P> 0.05);(4)在对应年龄段男性膝关节骨关节炎患者中,K-L分级0级与Ⅰ级的血清中雌二醇水平和睾酮差异均无显著意义(P> 0.05),0级、Ⅰ级分别与Ⅱ级的血清中雌二醇和睾酮水平差异均有显著意义(P <0.05);(5)对应年龄段男性膝关节骨关节炎严重程度与血清雌二醇水平(r_s=-0.476,P<0.05)和睾酮水平(r_s=-0.418,P<0.05)均呈现出明显的负相关性;(6)结果提示,绝经后女性早期膝关节骨关节炎严重程度与血清中雌二醇水平存在负相关;对应年龄段的男性早期膝关节骨关节炎严重程度与血清中雌二醇和睾酮水平均存在负相关。
BACKGROUND: The incidence of knee osteoarthritis(KOA) in postmenopausal females has been found to be higher than that in the males of the same age. The age and gender distribution suggests that there exists certain correlation between KOA pathogenesis and sex hormone levels. OBJECTIVE: To explore the correlation between sex hormone levels of the postmenopausal females and males of the same age, and early-stage KOA severity. METHODS: Forty-four KOA patients and 29 healthy people were enrolled. The subjects were divided into two groups by sex, including postmenopausal female group(n=37) and male group age(n=36). Each group was further subdivided by Kellgren-Lawrence K-L grading system, including subgroups of K-L 0, K-L Ⅰ and K-L Ⅱ. The serum estradiol and testosterone levels in each subgroup were detected by electrochemical luminescence method, and its association with K-L grade was analyzed. RESULTS AND CONCLUSION: In the postmenopausal female KOA patients, the serum estradiol level showed no significant difference between K-L 0 and K-L Ⅰ subgroups(P > 0.05), the level in the K-L 0 and K-L Ⅰ subgroups showed significant difference compared with the K-L Ⅱ subgroup(P < 0.05). The serum testosterone level showed no significant difference among groups in the postmenopausal female KOA patients(P > 0.05). The KOA severity showed a negative correlation with the serum estradiol level(r_s=-0.709, P < 0.05) but no correlation with the serum testosterone(P > 0.05). In the male KOA patients, the serum estradiol and testosterone levels showed no significant difference between K-L 0 and K-L I subgroups(P > 0.05), the levels in the K-L 0 and K-L Ⅰ subgroups showed significant difference compared with the K-L Ⅱ subgroup(P < 0.05). The KOA severity in male KOA patients showed a negative correlation with the serum estradiol level(r_s=-0.476, P < 0.05) and serum testosterone level(r_s=-0.418, P < 0.05). These results indicate that the severity of early-stage KOA shows a negative correlation with the serum estradiol level in the postmenopausal female patients and a negative correlation with the serum estradiol and testosterone levels in the males of the same age.
BACKGROUND: The incidence of knee osteoarthritis(KOA) in postmenopausal females has been found to be higher than that in the males of the same age. The age and gender distribution suggests that there exists certain correlation between KOA pathogenesis and sex hormone levels. OBJECTIVE: To explore the correlation between sex hormone levels of the postmenopausal females and males of the same age, and early-stage KOA severity. METHODS: Forty-four KOA patients and 29 healthy people were enrolled. The subjects were divided into two groups by sex, including postmenopausal female group(n=37) and male group age(n=36). Each group was further subdivided by Kellgren-Lawrence K-L grading system, including subgroups of K-L 0, K-L Ⅰ and K-L Ⅱ. The serum estradiol and testosterone levels in each subgroup were detected by electrochemical luminescence method, and its association with K-L grade was analyzed. RESULTS AND CONCLUSION: In the postmenopausal female KOA patients, the serum estradiol level showed no significant difference between K-L 0 and K-L Ⅰ subgroups(P > 0.05), the level in the K-L 0 and K-L Ⅰ subgroups showed significant difference compared with the K-L Ⅱ subgroup(P < 0.05). The serum testosterone level showed no significant difference among groups in the postmenopausal female KOA patients(P > 0.05). The KOA severity showed a negative correlation with the serum estradiol level(r_s=-0.709, P < 0.05) but no correlation with the serum testosterone(P > 0.05). In the male KOA patients, the serum estradiol and testosterone levels showed no significant difference between K-L 0 and K-L I subgroups(P > 0.05), the levels in the K-L 0 and K-L Ⅰ subgroups showed significant difference compared with the K-L Ⅱ subgroup(P < 0.05). The KOA severity in male KOA patients showed a negative correlation with the serum estradiol level(r_s=-0.476, P < 0.05) and serum testosterone level(r_s=-0.418, P < 0.05). These results indicate that the severity of early-stage KOA shows a negative correlation with the serum estradiol level in the postmenopausal female patients and a negative correlation with the serum estradiol and testosterone levels in the males of the same age.
引文
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[2]陆艳红,石晓兵,等.膝骨关节炎国内外流行病学研究现状及进展[J].中国中医骨伤科杂志,2012,20(6):81-84.
[3]Veronese N, Stubbs B, Solmi M, et al. Association between lower limb osteoarthritis and incidence of depressive symptoms:data from the osteoarthritis initiative. Age Ageing. 2017;46(3):470-476.
[4]Johnson VL. The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol. 2014;28(1):5-15.
[5]Kerkhof HJ, Doherty M, Arden NK, et al. Large-scale meta-analysis of interleukin-1 receptor antagoni st polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis. Osteoarthritis Cartilage. 2011;19(3):265-271.
[6]van den Bosch MH, Blom AB, van de Loo FA, et al. Brief Report:Induction of Matrix Metalloproteinase Expression by Synovial Wnt Signaling and Association With Disease Progression in Early Symptomatic Osteoarthritis. Arthritis Rheumatol. 2017;69(10):1978-1983
[7]李晓林,李彦林,马珂,等.SDF-1/CXCR4信号通路在骨性关节炎病理进程中的作用[J].中国组织工程研究与临床康复,2011,15(15):2805-2808.
[8]Chauffier K, Laiguillon MC, Bougault C, et al. Induction of the chemokine IL-8/Kc by the articular cartilage:possible influence on osteoarthritis. Joint Bone Spine. 2012;79(6):604-609.
[9]Blaney D, Davidson EN, Vitters EI, et al. Expression of transforming growth factor-β(TGF-β)and the TGF-βsignalling molecule SMAD-2P in spontaneous and instblitility-induced osteoarthritis role in cartilage degradation chondrogenesis and osteophyte formation. Ann Rheum Dis. 2006;65(11):1414-1421.
[10]Pereira RC, Costa-Pinto AR, Frias AM, et al. In vitro chondrogenic commitment of human Wharton's jelly stem cells by co-culture with human articular chondrocytes. J Tissue Eng Regen Med.2017; 11(6):1876-1887.
[11]Robinson DE, Buttle DJ, Short RD,et al.Glycosaminoglycan(GAG)binding surfaces for characterizing GAG-protein nteractions.Biomaterials.2012; 33(4):1007-1016.
[12]Zengini E, Finan C. The Genetic Epidemiological Landscape of Hip and Knee Osteoarthritis:Where Are We Now and Where Are We Going?. J Rheumatol. 2016;43(2):260-266.
[13]Pan Q, O'Connor MI, Coutts RD, et al. Characterization of osteoarthritic human knees indicates potential sex differences.Biol Sex Differ. 2016;7:27.
[14]Yan JY, Tian FM, Wang WY, et al. Age dependent changes in cartilage matrix, subchondral bone mass, and estradiol levels in blood serum, in naturally occurring osteoarthritis in Guinea pigs.Int J Mol Sci.2014; 15(8):13578-13595.
[15]Claassen H, Schicht M, Paulsen F. Impact of sex hormones,insulin, growth factors and peptides on cartilage health and disease. Prog Histochem Cytochem. 2011;45(4):239-293.
[16]Wise BL, Niu J, Zhang Y, et al. The association of parity with osteoarthritis and knee replacement in the multicenter osteoarthritis study. Osteoarthritis Cartilage. 2013; 21(12):1849-1854.
[17]Liao W, Li Z, Wang H, et al. Proteomic analysis of synovial fluid:insight into the pathogenesis of knee osteoarthritis. Int Orthop.2013;37(6):1045-1053.
[18]童干益.雌二醇、孕酮、抗HCG抗体联合检测在不孕症诊断中的临床意义[J].临床和实验医学杂志, 2010, 9(15):1152-1153.
[19]李卿,王书乐,张志斌.巨泌乳素血症患者血清性激素和甲状腺激素水平研究[J].国际检验医学杂志, 2017, 38(22):3097-3098.
[20]Tang X, Wang S, Zhan S, et al. The Prevalence of Symptomatic Knee Osteoarthritis in China:Results From the China Health and Retirement Longitudinal Study. Arthritis Rheumatol. 2016;68(3):648-653.
[21]余卫,徐苓,秦明伟,等.北京市城区老年人膝关节骨关节炎流行病学调查--与美国白种人膝关节骨关节炎的临床和X线比较分析[J].中华放射学杂志, 2005, 39(1):67-71.
[22]Prieto-Alhambra D, Judge A, Javaid MK, et al. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis:influences of age, gender and osteoarthritis affecting other joints.Ann Rheum Dis. 2014;73(9):1659-1664.
[23]Cho HJ, Morey V, Kang JY, et al. Prevalence and Risk Factors of Spine, Shoulder, Hand, Hip, and Knee Osteoarthritis in Community-dwelling Koreans Older Than Age 65 Years. Clin Orthop Relat Res. 2015;473(10):3307-3314.
[24]Zhang W, Nuki G, Moskowitz RW, et al. OARSI recommendations for the management of hip and knee osteoarthritis:Part III.Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage. 2010;18(4):476-499.
[25]Jin X, Wang BH, Wang X, et al. Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis. Osteoarthritis Cartilage. 2017;25(7):1100-1106.
[26]Ma HL, Blanchet TJ, Peluso D, et al. Osteoarthritis severity is sex dependent in a surgical mouse model. Osteoarthritis Cartilage.2007;15(6):695-700.
[27]Claassen H, Schünke M. Estradiol protects cultured articular chondrocytes from oxygen-radical-induced damage. Cell Tissue Res. 2005;319(3):439-445.
[28]Wang W, Wang L, Xu Z, et al. Effects of estradiol on reduction of osteoarthritis in rabbits through effect on matrix metalloproteinase proteins. Iran J Basic Med Sci. 2016;19(3):310-315.
[29]苏云,孟祥俊.卵巢切除联合过度运动制作骨性关节炎大鼠模型[J].中国组织工程研究,2012,16(15):2772-2775.
[30]Olson EJ, Lindgren BR. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.Bone. 2008;42(5):907-913.
[31]杨建辉,吕建国,申晓东.雌激素对骨关节炎模型软骨基质蛋白多糖变化的影响[J].西安交通大学学报(医学版),2004,25(6):584-586.
[32]Clowes JA, Eghbali-Fatourechi GZ, McCready L, et al. Estrogen action on bone marrow osteoclast lineage cells of postmenopausal women in vivo. Osteoporos Int. 2009;20(5):761-769.
[33]Yoldemir T, Erenus M. The impact of serum FSH and estradiol on postmenopausal osteoporosis related to time since menopause.Gynecol Endocrinol. 2012;28(11):884-888.
[34]Lewis R. Changes in Membrane Receptors and Ion Channels as Potential Biomarkers for Osteoarthritis. Front Physiol. 2015;6:357.
[35]Roh HL, Lee JS, Suh KT, et al. Association between estrogen receptor gene polymorphism and back pain intensity in female patients with degenerative lumbar spondylolisthesis. J Spinal Disord Tech. 2013; 26(2):E53-7
[36]Newman AB.Gender gap in longevity and disability in older persons. Epidemiol Rev. 2001;23(2):343-350.
[37]Irie T, Aizawa T. The role of sex hormones in the kinetics of chondrocytes in the growth plate A study in the rabbit. J Bone Joint Surg Br. 2005;87(9):1278-1284.
[38]Englert C, Blunk T, Fierlbeck J, et al. Steroid hormones strongly support bovine articular cartilage integration in the absence of interleukin-1beta. Arthritis Rheum. 2006;54(12):3890-3897.
[39]Sasano H, Uzuki M, Sawai T, et al. Aromatase in human bone tissue. J Bone Miner Res. 1997;12(9):1416-231423.
[40]Schicht M, Ernst J, Nielitz A, et al. Articular cartilage chondrocytes express aromatase and use enzymes involved in estrogen metabolism. Arthritis Res Ther. 2014;16(2):R93
[41]Dolomie-Fagour L, Gatta B, Nguyen TD. Bioavailable estradiol in man:relationship with age and testosterone. Clin Chim Acta.2008;398(1-2):145-147.
[42]Hernández JL, Garcés CM, Sumillera M, et al. Aromatase expression in osteoarthritic and osteoporotic bone. Arthritis Rheum. 2008;58(6):1696-1700.
[2]陆艳红,石晓兵,等.膝骨关节炎国内外流行病学研究现状及进展[J].中国中医骨伤科杂志,2012,20(6):81-84.
[3]Veronese N, Stubbs B, Solmi M, et al. Association between lower limb osteoarthritis and incidence of depressive symptoms:data from the osteoarthritis initiative. Age Ageing. 2017;46(3):470-476.
[4]Johnson VL. The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol. 2014;28(1):5-15.
[5]Kerkhof HJ, Doherty M, Arden NK, et al. Large-scale meta-analysis of interleukin-1 receptor antagoni st polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis. Osteoarthritis Cartilage. 2011;19(3):265-271.
[6]van den Bosch MH, Blom AB, van de Loo FA, et al. Brief Report:Induction of Matrix Metalloproteinase Expression by Synovial Wnt Signaling and Association With Disease Progression in Early Symptomatic Osteoarthritis. Arthritis Rheumatol. 2017;69(10):1978-1983
[7]李晓林,李彦林,马珂,等.SDF-1/CXCR4信号通路在骨性关节炎病理进程中的作用[J].中国组织工程研究与临床康复,2011,15(15):2805-2808.
[8]Chauffier K, Laiguillon MC, Bougault C, et al. Induction of the chemokine IL-8/Kc by the articular cartilage:possible influence on osteoarthritis. Joint Bone Spine. 2012;79(6):604-609.
[9]Blaney D, Davidson EN, Vitters EI, et al. Expression of transforming growth factor-β(TGF-β)and the TGF-βsignalling molecule SMAD-2P in spontaneous and instblitility-induced osteoarthritis role in cartilage degradation chondrogenesis and osteophyte formation. Ann Rheum Dis. 2006;65(11):1414-1421.
[10]Pereira RC, Costa-Pinto AR, Frias AM, et al. In vitro chondrogenic commitment of human Wharton's jelly stem cells by co-culture with human articular chondrocytes. J Tissue Eng Regen Med.2017; 11(6):1876-1887.
[11]Robinson DE, Buttle DJ, Short RD,et al.Glycosaminoglycan(GAG)binding surfaces for characterizing GAG-protein nteractions.Biomaterials.2012; 33(4):1007-1016.
[12]Zengini E, Finan C. The Genetic Epidemiological Landscape of Hip and Knee Osteoarthritis:Where Are We Now and Where Are We Going?. J Rheumatol. 2016;43(2):260-266.
[13]Pan Q, O'Connor MI, Coutts RD, et al. Characterization of osteoarthritic human knees indicates potential sex differences.Biol Sex Differ. 2016;7:27.
[14]Yan JY, Tian FM, Wang WY, et al. Age dependent changes in cartilage matrix, subchondral bone mass, and estradiol levels in blood serum, in naturally occurring osteoarthritis in Guinea pigs.Int J Mol Sci.2014; 15(8):13578-13595.
[15]Claassen H, Schicht M, Paulsen F. Impact of sex hormones,insulin, growth factors and peptides on cartilage health and disease. Prog Histochem Cytochem. 2011;45(4):239-293.
[16]Wise BL, Niu J, Zhang Y, et al. The association of parity with osteoarthritis and knee replacement in the multicenter osteoarthritis study. Osteoarthritis Cartilage. 2013; 21(12):1849-1854.
[17]Liao W, Li Z, Wang H, et al. Proteomic analysis of synovial fluid:insight into the pathogenesis of knee osteoarthritis. Int Orthop.2013;37(6):1045-1053.
[18]童干益.雌二醇、孕酮、抗HCG抗体联合检测在不孕症诊断中的临床意义[J].临床和实验医学杂志, 2010, 9(15):1152-1153.
[19]李卿,王书乐,张志斌.巨泌乳素血症患者血清性激素和甲状腺激素水平研究[J].国际检验医学杂志, 2017, 38(22):3097-3098.
[20]Tang X, Wang S, Zhan S, et al. The Prevalence of Symptomatic Knee Osteoarthritis in China:Results From the China Health and Retirement Longitudinal Study. Arthritis Rheumatol. 2016;68(3):648-653.
[21]余卫,徐苓,秦明伟,等.北京市城区老年人膝关节骨关节炎流行病学调查--与美国白种人膝关节骨关节炎的临床和X线比较分析[J].中华放射学杂志, 2005, 39(1):67-71.
[22]Prieto-Alhambra D, Judge A, Javaid MK, et al. Incidence and risk factors for clinically diagnosed knee, hip and hand osteoarthritis:influences of age, gender and osteoarthritis affecting other joints.Ann Rheum Dis. 2014;73(9):1659-1664.
[23]Cho HJ, Morey V, Kang JY, et al. Prevalence and Risk Factors of Spine, Shoulder, Hand, Hip, and Knee Osteoarthritis in Community-dwelling Koreans Older Than Age 65 Years. Clin Orthop Relat Res. 2015;473(10):3307-3314.
[24]Zhang W, Nuki G, Moskowitz RW, et al. OARSI recommendations for the management of hip and knee osteoarthritis:Part III.Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage. 2010;18(4):476-499.
[25]Jin X, Wang BH, Wang X, et al. Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis. Osteoarthritis Cartilage. 2017;25(7):1100-1106.
[26]Ma HL, Blanchet TJ, Peluso D, et al. Osteoarthritis severity is sex dependent in a surgical mouse model. Osteoarthritis Cartilage.2007;15(6):695-700.
[27]Claassen H, Schünke M. Estradiol protects cultured articular chondrocytes from oxygen-radical-induced damage. Cell Tissue Res. 2005;319(3):439-445.
[28]Wang W, Wang L, Xu Z, et al. Effects of estradiol on reduction of osteoarthritis in rabbits through effect on matrix metalloproteinase proteins. Iran J Basic Med Sci. 2016;19(3):310-315.
[29]苏云,孟祥俊.卵巢切除联合过度运动制作骨性关节炎大鼠模型[J].中国组织工程研究,2012,16(15):2772-2775.
[30]Olson EJ, Lindgren BR. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.Bone. 2008;42(5):907-913.
[31]杨建辉,吕建国,申晓东.雌激素对骨关节炎模型软骨基质蛋白多糖变化的影响[J].西安交通大学学报(医学版),2004,25(6):584-586.
[32]Clowes JA, Eghbali-Fatourechi GZ, McCready L, et al. Estrogen action on bone marrow osteoclast lineage cells of postmenopausal women in vivo. Osteoporos Int. 2009;20(5):761-769.
[33]Yoldemir T, Erenus M. The impact of serum FSH and estradiol on postmenopausal osteoporosis related to time since menopause.Gynecol Endocrinol. 2012;28(11):884-888.
[34]Lewis R. Changes in Membrane Receptors and Ion Channels as Potential Biomarkers for Osteoarthritis. Front Physiol. 2015;6:357.
[35]Roh HL, Lee JS, Suh KT, et al. Association between estrogen receptor gene polymorphism and back pain intensity in female patients with degenerative lumbar spondylolisthesis. J Spinal Disord Tech. 2013; 26(2):E53-7
[36]Newman AB.Gender gap in longevity and disability in older persons. Epidemiol Rev. 2001;23(2):343-350.
[37]Irie T, Aizawa T. The role of sex hormones in the kinetics of chondrocytes in the growth plate A study in the rabbit. J Bone Joint Surg Br. 2005;87(9):1278-1284.
[38]Englert C, Blunk T, Fierlbeck J, et al. Steroid hormones strongly support bovine articular cartilage integration in the absence of interleukin-1beta. Arthritis Rheum. 2006;54(12):3890-3897.
[39]Sasano H, Uzuki M, Sawai T, et al. Aromatase in human bone tissue. J Bone Miner Res. 1997;12(9):1416-231423.
[40]Schicht M, Ernst J, Nielitz A, et al. Articular cartilage chondrocytes express aromatase and use enzymes involved in estrogen metabolism. Arthritis Res Ther. 2014;16(2):R93
[41]Dolomie-Fagour L, Gatta B, Nguyen TD. Bioavailable estradiol in man:relationship with age and testosterone. Clin Chim Acta.2008;398(1-2):145-147.
[42]Hernández JL, Garcés CM, Sumillera M, et al. Aromatase expression in osteoarthritic and osteoporotic bone. Arthritis Rheum. 2008;58(6):1696-1700.