绝经后活动性类风湿性关节炎患者低骨密度的相关危险因素分析
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摘要
目的分析绝经后活动性类风湿性关节炎(rheumatoid arthritis,RA)患者出现低骨密度相关的危险因素。方法研究对象为106例患有活动性RA的绝经后妇女,患者按体质量指数(BMI)分组:I组消瘦(18.5～24.9 kg/m~2,n=36),II组超重(25.0～29.9 kg/m~2,n=35),III组肥胖(>30.0 kg/m~2,n=35)。检测这些患者的股骨BMD和血清BTM水平:骨钙素(OC)和I型胶原交联C-端肽片段(CTX)和骨桥蛋白(OPN)、抵抗素、高敏C反应蛋白、白细胞介素-6、肿瘤坏死因子(TNF)-a。结果与较瘦的女性相比,肥胖女性的总股骨BMD和总T评分显然更高(P<0.05);发现BMD和CTX水平与体重存在显著相关性(P<0.05)。调整股骨颈BMD后,BMI与TNF-α水平呈负相关(P<0.05)。骨钙素水平与抵抗素呈负相关(P<0.05),CTX水平与OPN呈正相关(P<0.05);并发现BTM和BMD与其他炎症指标之间的关联。观察到OPN水平与体重、腰围和绝经后时间之间呈负相关性(P<0.05)。结论本研究结果表明,体重和OPN、抵抗素和TNF-α在绝经后活动性RA患者的骨密度降低中起重要作用。
Objective To analyze the risk factors associated with low bone mineral density in postmenopausal patients with active rheumatoid arthritis(RA). Methods A total of 106 postmenopausal women with active RA were studied. Patients were grouped by body mass index(BMI): group I was lean(18.5-24.9 kg/m~2,n=36), group II was overweight(25.0-29.9 kg/m~2, n=35), group III was obese(>30.0 kg/m~2, n=35). The femoral BMD and serum levels of BTMs: osteocalcin(OC), collagen type I cross-linked C-telopeptide fragments(CTX), osteopontin(OPN), resistin, high sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-a(TNF-a)were measured in these patients. Results Femoral BMD and total T-score were significantly higher in obese women than in lean subjects(P<0.05). BMD and CTX levels were significantly associated with body mass parameters(P<0.05, respectively). After adjusting femoral neck BMD, BMI was negatively associated with the TNF-a levels(P<0.05). Osteocalcin level was negatively correlated with resistin(P<0.05). CTX level was positively correlated with OPN(P<0.05). There were associations between BTM and BMD and other inflammatory indices. OPN was negatively correlated with body weight(P<0.05), waist circumference(P<0.05), and duration of postmenopausal period(P<0.05). Conclusion The present study suggests that body weight, OPN, resistin, and TNF-a play an important role in lowering BMD in postmenopausal women with active RA.
Objective To analyze the risk factors associated with low bone mineral density in postmenopausal patients with active rheumatoid arthritis(RA). Methods A total of 106 postmenopausal women with active RA were studied. Patients were grouped by body mass index(BMI): group I was lean(18.5-24.9 kg/m~2,n=36), group II was overweight(25.0-29.9 kg/m~2, n=35), group III was obese(>30.0 kg/m~2, n=35). The femoral BMD and serum levels of BTMs: osteocalcin(OC), collagen type I cross-linked C-telopeptide fragments(CTX), osteopontin(OPN), resistin, high sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-a(TNF-a)were measured in these patients. Results Femoral BMD and total T-score were significantly higher in obese women than in lean subjects(P<0.05). BMD and CTX levels were significantly associated with body mass parameters(P<0.05, respectively). After adjusting femoral neck BMD, BMI was negatively associated with the TNF-a levels(P<0.05). Osteocalcin level was negatively correlated with resistin(P<0.05). CTX level was positively correlated with OPN(P<0.05). There were associations between BTM and BMD and other inflammatory indices. OPN was negatively correlated with body weight(P<0.05), waist circumference(P<0.05), and duration of postmenopausal period(P<0.05). Conclusion The present study suggests that body weight, OPN, resistin, and TNF-a play an important role in lowering BMD in postmenopausal women with active RA.
引文
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[15] Barnabe C,Hanley DA.Effect of tumor necrosis factor alpha inhibition on bone density and turnover markers in patients with rheumatoid arthritis and spondyloarthropathy[J].Semin Arthritis Rheum,2010,39(2):116-122.
[16] Haugen F,J?rgensen A,Drevon CA,et al.Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes[J].Febs Letters,2001,507(1):105-108.
[17] Thommesen L,Stunes AM,Grosvik K,et al.Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism[J].J Cell Biochem,2010,99(3):824-834.
[18] Seriolo B,Ferretti V,Sulli A,et al.Serum osteocalcin levels in premenopausal rheumatoid arthritis patients[J].Ann N Y Acad Sci,2010,966(1):502-507.
[19] Chang IC,Chiang TI,Yeh KT,et al.Increased serum osteopontin is a risk factor for osteoporosis in menopausal women[J].Osteoporos Int,2010,21(8):1401-1409.
[20] Gómez-Ambrosi J,Catalán V,Ramírez B,et al.Plasma osteopontin levels and expression in adipose tissue are increased in obesity[J].J Clin Endocrinol Metab,2007,92(9):3719.
[21] Mil AHMvdH,Kooij SMVD,Allaart CF,et al.A high body mass index has a protective effect on the amount of joint destruction in small joints in early rheumatoid arthritis[J].Ann Rheum Dis,2008,67(6):769-774.
[2] Kanis JA,Cooper C,Baim S,et al.Interpretation and use of FRAX in clinical practice[J].Osteoporos Int,2011,22(9):2395-2411.
[3] Glendenning P.Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment:a need for international reference standards[J].Clin Biochem Rev,2011,22(2):391-420.
[4] Book C,Karlsson M,?kesson K,et al.Disease activity and disability but probably not glucocorticoid treatment predicts loss in bone mineral density in women with early rheumatoid arthritis[J].Scand J Rheumatol,2008,37(4):248.
[5] Le GB,Blanchard F,Berthelot JM,et al.Role for interleukin-6 in structural joint damage and systemic bone loss in rheumatoid arthritis[J].Joint Bone Spine,2010,77(3):201-205.
[6] Bokarewa M,Nagaev I,Dahlberg L,et al.Resistin,an adipokine with potent proinflammatory properties[J].J Immunol,2005,174(9):5789.
[7] Almehed K,D'Elia HF,Bokarewa M,et al.Role of resistin as a marker of inflammation in systemic lupus erythematosus[J].Arthritis Res Ther,2008,10(1):R15.
[8] Migita K,Maeda Y,Miyashita T,et al.The serum levels of resistin in rheumatoid arthritis patients[J].Clin Exp Rheumatol,2006,24(6):698-701.
[9] Scatena M,Liaw L,Giachelli CM.Osteopontin:a multifunctional molecule regulating chronic inflammation and vascular disease[J].Arterioscler Thromb Vasc Biol,2007,27(11):2302.
[10] Finkelstein JS,Brockwell SE,Mehta V,et al.Bone mineral density changes during the menopause transition in a multiethnic cohort of women[J].J Clin Endocrinol Metab,2008,93(3):861-868.
[11] Baker JF,George M,Baker DG,et al.Associations between body mass,radiographic joint damage,adipokines and risk factors for bone loss in rheumatoid arthritis[J].Rheumatology,2011,50(11):2100.
[12] Garnero P,Delmas PD.Contribution of bone mineral density and bone turnover markers to the estimation of risk of osteoporotic fracture in postmenopausal women [J].J Musculoskelet Neuronal Interact,2004,4(1):50-63.
[13] Symmons Deborah PM,Silman AJ,Karl G,et al.Influence of arthritis and non-arthritis related factors on areal bone mineral density (BMDa) in women with longstanding inflammatory polyarthritis:a primary care based inception cohort[J].BMC Musculoskelet Disord,2010,11(1):1-6.
[14] Ishii T,Ohshima S,Ishida T,et al.Osteopontin as a positive regulator in the osteoclastogenesis of arthritis[J].Biochem Biophys Res Commun,2004,316(3):809-815.
[15] Barnabe C,Hanley DA.Effect of tumor necrosis factor alpha inhibition on bone density and turnover markers in patients with rheumatoid arthritis and spondyloarthropathy[J].Semin Arthritis Rheum,2010,39(2):116-122.
[16] Haugen F,J?rgensen A,Drevon CA,et al.Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes[J].Febs Letters,2001,507(1):105-108.
[17] Thommesen L,Stunes AM,Grosvik K,et al.Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism[J].J Cell Biochem,2010,99(3):824-834.
[18] Seriolo B,Ferretti V,Sulli A,et al.Serum osteocalcin levels in premenopausal rheumatoid arthritis patients[J].Ann N Y Acad Sci,2010,966(1):502-507.
[19] Chang IC,Chiang TI,Yeh KT,et al.Increased serum osteopontin is a risk factor for osteoporosis in menopausal women[J].Osteoporos Int,2010,21(8):1401-1409.
[20] Gómez-Ambrosi J,Catalán V,Ramírez B,et al.Plasma osteopontin levels and expression in adipose tissue are increased in obesity[J].J Clin Endocrinol Metab,2007,92(9):3719.
[21] Mil AHMvdH,Kooij SMVD,Allaart CF,et al.A high body mass index has a protective effect on the amount of joint destruction in small joints in early rheumatoid arthritis[J].Ann Rheum Dis,2008,67(6):769-774.