Email Alert | RSS

北京大学学报（医学版） ›› 2018, Vol. 50 ›› Issue (6): 998-1003. doi: 10.19723/j.issn.1671-167X.2018.06.010

• 论著 • 上一篇    下一篇

初发系统性红斑狼疮患者骨密度及血清骨转化因子的研究

姚海红1,唐素玫1,王志敏1,张霞1,陈绪勇1,高莉1,刘婧1,戴逸君1,胡肇衡2,张学武(),栗占国1   

  1. 北京大学人民医院 1. 风湿免疫科, 2. 内分泌科, 北京 100044
  • 收稿日期:2018-08-27 出版日期:2018-12-18 发布日期:2018-12-18
  • 通讯作者: 张学武 E-mail:xuewulore@163.com
  • 基金资助:
    国家自然科学基金(81801618)

Study of bone mineral density and serum bone turnover markers in newly diagnosed systemic lupus erythematosus patients

Hai-hong YAO1,Su-mei TANG1,Zhi-min WANG1,Xia ZHANG1,Xu-yong CHEN1,Li GAO1,Jing LIU1,Yi-jun DAI1,Zhao-heng HU2,Xue-wu ZHANG(),Zhan-guo LI1   

  1. 1. Department of Rheumatology and Immunology, 2. Department of Endocrinology, Peking University People’s Hospital,Beijing 100044, China
  • Received:2018-08-27 Online:2018-12-18 Published:2018-12-18
  • Contact: Xue-wu ZHANG E-mail:xuewulore@163.com
  • Supported by:
    Supported by the National Natural Science Foundation of China(81801618)

RICH HTML

   

PDF (PC)

摘要：

目的: 探讨初发系统性红斑狼疮(systemic lupus erythematosus, SLE)患者骨密度及血清骨转化因子的变化情况。方法: 选取在北京大学人民医院风湿免疫科住院的初发SLE患者80例,正常健康志愿者80例,入组研究时所有SLE患者均未开始服用糖皮质激素、免疫抑制剂及活性维生素D。使用双光能X线吸收法检测前臂、髋部、腰椎骨密度,使用ELISA方法检测血清抗酒石酸酸性磷酸酶(tartaric acid phosphatase 5b,TRAP5b)、骨碱性磷酸酶(bone alkaline phosphatase,BAP)和25羟维生素D3(25-dihydroxy-vitamin D3,25-OH-VD3)水平。通过Logistic回归分析寻找SLE患者骨密度下降的可能因素。结果: SLE患者平均年龄(32.8±12.4)岁,育龄期女性68例,年龄未超过50岁的男性12例;健康对照组平均年龄(30.0±2.9)岁,育龄期女性70例,年龄未超过50岁的男性10例。SLE患者前臂、腰椎、髋部平均骨密度均显著低于正常对照组,总体骨密度减低发生率为20%。血清骨转化因子方面,SLE患者血清BAP浓度与同年龄的健康对照相似,血清TRAP5b水平显著低于正常对照(P=0.001),血清25-OH-VD3水平显著低于正常对照[(46.1±12.3) nmol/L vs. (25.4±11.2) nmol/L, P<0.001]。存在肾炎的SLE患者血清25-OH-VD3显著低于不存在肾炎的SLE患者(P=0.04)。上述指标同SLE病情活动度的关系提示,血清25-OH-VD3水平与SLE疾病活动指数(SLE disease activity index, SLEDAI)负相关(r=-0.3, P=0.001),血清TRAP5b浓度与SLEDAI正相关(r=0.435, P=0.003)。Logistic回归分析显示,年龄(P=0.058)及SLEDAI评分(P=0.085)可能与SLE患者骨密度减低有关。结论: 初发SLE患者骨密度值较正常对照下降,疾病相关的慢性炎症可能是参与SLE骨密度减低的危险因素。

关键词: 红斑狼疮,系统性, 骨密度, 骨转化标志物

Abstract:

Objective: To investigate the changes of bone mineral density (BMD) and serum bone turnover factor in newly diagnosed systemic lupus erythematous (SLE) patients.Methods:Eighty newly diagnosed SLE patients and 80 age and gender matched healthy controls were enrolled. None of the SLE patients had ever received glucocorticoid,immunosuppressive agents or vitamin D. BMD was measured at radius,lumbar spine and hip by dual X ray absorptiometry (DXA). Bone turnover markers including se-rum levels of tartrate-resistant acid phosphatase 5b (TRAP5b),bone alkaline phosphatase (BAP) and 25-hydroxy vitamin D3 (25-OH-VD3) were measured by enzyme-linked immunosorbent assay (ELISA). Logistic regression was employed to analyze the risk factors associated with decreased BMD.Results:Mean age of the SLE patients was (32.8±12.4) years,and 85% were female,none of whom were post-menopausal. BMD was significantly reduced in all the measured sites,compared with the healthy controls. Sixteen (20%) of the patients were osteopenic in at least one site measured locations. The serum levels of 25-OH-VD3 were markedly reduced in the newly diagnosed SLE patients than those of the normal controls [(46.1+12.3) nmol/L vs. (25.4+11.2) nmol/L,P<0.001)]. The serum levels of 25-OH-VD3 in the SLE patients with nephritis were much lower than those without nephritis (P=0.04). A significant negative correlation was demonstrated between the serum concentration of 25-OH-VD3 and the disease activity scores as measured by SLE disease activity index (SLEDAI) (r=-0.3,P=0.001). The serum TRAP5b concentration was positively correlated with SLEDAI (r=0.435,P=0.003). Age (P=0.058) and SLEDAI (P=0.085) were probably associated with decreased BMD in Logistic regression analysis.Conclusion:The study showed reduced BMD in untreated SLE patients. The role of chro-nic inflammation was of probable importance in bone metabolism.

Key words: Lupus erythematosus,systemic, Bone density, Bone turnover markers

中图分类号: 

  • R593.241

表1

初发SLE患者及健康对照组的基线特征"

Items SLE patients (n=80) Health control (n=80) P value
Age/years, x-±s 32.8±12.4 30.2±4.5 0.08
Females, n (%) 68 (85) 70 (87.5) 0.82
Postmenopause of woman, n (%) 0 0
Bodymass index/(kg/m2), x-±s 22.1±2.9 21.3±3.0 0.07
Ever smoking, n (%) 2 (2.4) 0 0.5
Disease duration/months,median (P25, P75) 7 (2, 22.5)
SLEDAI score, x-±s 16±8
Vitamin intake/(μg/d) 0 0

表2

初发SLE患者及与其年龄、性别相匹配的健康对照组的骨密度"

Items Bone mineral density/(g/cm2), x-±s P value
SLE patients (n=80) Health control (n=80)
Lumbar spine
Total 0.929±0.143 1.008±0.107 <0.001
L1 0.892±0.116 0.917±0.102 0.150
L2 0.966±0.105 1.010±0.112 0.011
L3 0.978±0.131 1.047±0.111 <0.001
L4 0.985±0.162 1.039±0.121 0.018
Hip
Total hip 0.901±0.130 0.939±0.107 0.045
Neck 0.801±0.136 0.792±0.096 0.629
Ward’s triangle 0.773±0.165 0.747±0.121 0.256
Intertrochanter 1.130±0.098 1.125±0.126 0.779
Trochanter 0.712±0.102 0.701±0.097 0.486
Radius (Left) 0.692±0.058 0.701±0.058 0.034

图1

初发SLE患者及健康对照组的骨代谢情况(n=80)"

图2

血清25-OH-VD3与疾病活动度、血清学指标及脏器损伤的相关性"

表3

初发SLE患者骨密度减低危险因素的Logistic回归分析"

Risk factors B SE P value OR (95%CI)
Age 0.026 0.023 0.249 1.027 (0.981,1.074)
Disease duration 0.041 0.022 0.058 1.042 (0.999,1.087)
Gender -0.678 0.956 0.478 0.508 (0.078,3.303)
SLEDAI 0.073 0.042 0.085 1.076 (0.990,1.169)
TRAP5b 0.173 0.242 0.475 1.189 (0.74,1.909)
BAP -0.004 0.046 0.926 0.996 (0.910,1.089)
25-OH-VD3 -0.054 0.508 0.187 0.948 (0.875,1.026)
[1] Hochberg MC . Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus[J]. Arthritis Rheum, 1997,40(9):1725.
[2] Guo Q, Fan P, Luo J , et al. Assessment of bone mineral density and bone metabolism in young male adults recently diagnosed with systemic lupus erythematosus in China[J]. Lupus, 2017,26(3):289-293.
doi: 10.1177/0961203316664596 pmid: 27522093
[3] Boyanov M, Robeva R, Popivanov P . Bone mineral density changes in women with systemic lupus erythematosus[J]. Clin Rheumatol, 2003,22(4-5):318-323.
doi: 10.1007/s10067-003-0743-0 pmid: 14579164
[4] Coimbra IB, Costallat LT . Bone mineral density in systemic lupus erythematosus and its relation to age at disease onset, plasmatic estradiol and immunosuppressive therapy[J]. Joint Bone Spine, 2003,70(1):40-45.
doi: 10.1016/S1297-319X(02)00009-X pmid: 12639616
[5] Almehed K , Forsblad dH, Kvist G, et al. Prevalence and risk factors of osteoporosis in female SLE patients-extended report[J]. Rheumatology (Oxford), 2007,46(7):1185-1190.
doi: 10.1093/rheumatology/kem105 pmid: 17500075
[6] Furukawa M, Kiyohara C, Tsukamoto H , et al. Prevalence of and risk factors for low bone mineral density in Japanese female patients with systemic lupus erythematosus[J]. Rheumatol Int, 2011,31(3):365-376.
doi: 10.1007/s00296-009-1244-5 pmid: 20020143
[7] Cramarossa G, Urowitz MB, Su J , et al. Prevalence and associa-ted factors of low bone mass in adults with systemic lupus erythematosus[J]. Lupus, 2017,26(4):365-372.
doi: 10.1177/0961203316664597 pmid: 27522094
[8] Compeyrot-Lacassagne S, Tyrrell PN, Atenafu E , et al. Prevalence and etiology of low bone mineral density in juvenile systemic lupus erythematosus[J]. Arthritis Rheum, 2007,56(6):1966-1973.
doi: 10.1002/art.22691 pmid: 17530722
[9] Alsufyani KA, Ortiz-Alvarez O, Cabral DA , et al. Bone mineral density in children and adolescents with systemic lupus erythematosus, juvenile dermatomyositis, and systemic vasculitis: relationship to disease duration, cumulative corticosteroid dose, calcium intake, and exercise[J]. J Rheumatol, 2005,32(4):729-733.
doi: 10.1097/01.rhu.0000158687.22004.18 pmid: 15801032
[10] Lilleby V, Lien G, Frey FK , et al. Frequency of osteopenia in children and young adults with childhood-onset systemic lupus erythematosus[J]. Arthritis Rheum, 2005,52(7):2051-2059.
doi: 10.1002/(ISSN)1529-0131
[11] Ureña P, Hruby M, Ferreira A , et al. Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients[J]. J Am Soc Nephrol, 1996,7(3):506-512.
doi: 10.1046/j.1464-410X.1996.96837.x pmid: 8704118
[12] Shidara K, Inaba M, Okuno S , et al. Serum levels of TRAP5b, a new bone resorption marker unaffected by renal dysfunction, as a useful marker of cortical bone loss in hemodialysis patients[J]. Calcif Tissue Int, 2008,82(4):278-287.
doi: 10.1007/s00223-008-9127-4 pmid: 18421493
[13] Keronen S, Martola L, Finne P , et al. Bone histomorphometry and indicators of bone and mineral metabolism in wait-listed dialysis patients[J]. Clin Nephrol, 2016,85(3):127-134.
doi: 10.5414/CN108709 pmid: 26833298
[14] Dhillon VB, Davies MC, Hall ML , et al. Assessment of the effect of oral corticosteroids on bone mineral density in systemic lupus erythematosus: a preliminary study with dual energy X ray absorptiometry[J]. Ann Rheum Dis, 1990,49(8):624-626.
doi: 10.1136/ard.49.8.624
[15] Breslin LC, Magee PJ, Wallace JM , et al. An evaluation of vitamin D status in individuals with systemic lupus erythematosus[J]. Proc Nutr Soc, 2011,70(4):399-407.
doi: 10.1017/S0029665111001613 pmid: 21861947
[16] Bartels LE, Hvas CL, Agnholt J , et al. Human dendritic cell antigen presentation and chemotaxis are inhibited by intrinsic 25-hydroxy vitamin D activation[J]. Int Immunopharmacol, 2010,10(8):922-928.
doi: 10.1016/j.intimp.2010.05.003 pmid: 20483384
[17] Jirapongsananuruk O, Melamed I, Leung DY . Additive immunosuppressive effects of 1, 25-dihydroxy vitamin D3 and corticosteroids on TH1, but not TH2, responses[J]. J Allergy Clin Immunol, 2000,106(5):981-985.
doi: 10.1067/mai.2000.110101 pmid: 11080724
[18] Correale J, Ysrraelit MC, Gaitán MI . Immunomodulatory effects of vitamin D in multiple sclerosis[J]. Brain, 2009,132(Pt 5):1146-1160.
doi: 10.1093/brain/awp033 pmid: 19321461
[19] Ruiz-Irastorza G, Gordo S, Olivares N , et al. Changes in vitamin D levels in patients with systemic lupus erythematosus: Effects on fatigue, disease activity, and damage[J]. Arthritis Care Res (Hoboken), 2010,62(8):1160-1165.
doi: 10.1002/acr.20186 pmid: 20235208
[1] 王鹏,吴华,车颖,范东伟,刘珏,陶立元. 亚洲骨质疏松筛查工具在健康体检中的筛查准确性评价及适宜切点研究[J]. 北京大学学报（医学版）, 2019, 51(6): 1085-1090.
[2] 曹婕1，孟焕新. 锥形束CT用于评估牙槽骨骨缺损的情况和骨再生区域骨密度的变化[J]. 北京大学学报(医学版), 2018, 50(1): 110-116.
[3] 王昱，郝燕捷，邓雪蓉，李光韬，耿研，赵娟，周炜，张卓莉. 类风湿关节炎患者骨量改变危险因素分析及FRAX的应用价值[J]. 北京大学学报(医学版), 2015, 47(5): 781-786.
[4] 王昱，耿研，邓雪蓉，张卓莉. 女性类风湿关节炎患者手腕骨密度检查与超声腕关节骨侵蚀及炎症评分的相关性[J]. 北京大学学报(医学版), 2015, 47(5): 774-780.
[5] 王昱，周炜，郝燕捷，李光韬，邓雪蓉，赵娟，张卓莉. 跟骨定量超声在筛查结缔组织病患者合并骨质疏松中的应用[J]. 北京大学学报（医学版）, 2013, 45(5): 766-769.
[6] 郑旭, 林久祥. 牙槽骨密度定量测量系统的建立及测量精确性、有效性的检验[J]. 北京大学学报（医学版）, 2008, 40(4): 431-436.
[7] 李斌斌, 于世凤. 锌离子对牙各矿化成份破骨细胞性吸收的体外调控[J]. 北京大学学报（医学版）, 2006, 38(6): 644-647.
[8] 李荣昌, 杨惠雯, 王夔. 低剂量长期饲喂La(NO3)3后La在大鼠骨中的蓄积及骨微结构的改变[J]. 北京大学学报（医学版）, 2003, 35(6): 622-624.
[9] 杨欣, 林守清, 白文佩, 余卫, 陈淑玲, 沈英, 郑淑蓉. 雌孕激素联合疗法对绝经后妇女骨密度和血脂的影响[J]. 北京大学学报（医学版）, 2002, 34(3): 294-297.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
ISSN 1671-167X
CN 11-4691/R
主管单位：中华人民共和国教育部
主办单位：北京大学
地址： 北京市海淀区学院路38号 北京大学医学部 《北京大学学报（医学版）》
邮编：100191
电话：010-82801551
Email： xbbjb2@bjmu.edu.cn

《北京大学学报（医学版）》
微信公众号
版权所有 © 2018 《北京大学学报（医学版）》编辑部