社区女性骨质疏松症的现状调查及影响骨密度的生化因子研究
|
摘要
第一章社区女性骨质疏松症现状及相关因素调查研究
目的了解长沙市社区未绝经、围绝经期、绝经后女性的骨质疏松发生率及相关因素,以期发现影响社区女性居民骨密度的危险因素和保护因素,为疾病社区防治提供依据。
方法采用整群随机抽样方法分别从中南勘察设计院生活社区、长沙马王堆社区、湘雅医院生活社区抽取样本,对其中常住户口年龄在20～80岁、符合纳入标准的社区女性调查员按自制调查表的调查内容入户实施调查,并陪同调查对象去医院进行体重指数、骨密度等调查指标的检查。分析社区未绝经,围绝经期及绝经后女性骨质疏松患病率及其与年龄、绝经状态的关系,深入研究影响女性骨质疏松症的相关因素。采用Epidata3.0建立数据库,应用SPSS13.0统计软件包进行数据的统计分析。
结果长沙市社区女性的骨质疏松症的总患病率为17.0%,40岁以下年龄段的患病率为0.3%。40岁～年龄段的患病率为5.4%;50岁～年龄段的患病率为20.1%;60岁～年龄段的患病率为44.8%;70岁～年龄段的患病率为70.0%。绝经后妇女骨质疏松患病率高于未绝经妇女骨质疏松患病率,前者为后者的22.9倍。社区绝经妇女骨质疏松的患病率随着年龄、绝经年限的延长而增加。采用非条件logistic回归分析发现骨质疏松症的危险因素为年龄大(OR=1.832)、初潮年龄晚(OR=2.589)、已绝经(OR=1.507)、绝经年限长(OR=2.168)、生产次数多(OR=1.449),保护因素为高体重指数(OR=0.514)和经常运动(OR=0.484)。
结论长沙社区女性骨质疏松症的患病率随年龄和绝经年限的增加相应增加;已绝经女性的骨质疏松症的患病率最高,围绝经期女性次之,未绝经女性最低。与骨质疏松症有关的危险因素为年龄大、初潮年龄晚、生产次数多、已绝经、绝经年限长,保护因素为高体重指数和经常运动。
第二章绝经后妇女肥胖相关指标、相关脂肪因子与骨密度的关系研究
目的低体重指数是骨质疏松症的危险因素,低体重指数人群脂肪组织减少。最近研究表明脂肪细胞分泌因子可调控骨代谢。脂肪细胞分泌因子(简称脂肪因子)主要有脂联素(Adiponectin)、瘦素(Leptin)、抵抗素(Resistin)、Apelin、内脏脂肪素(Visfatin)。我们进一步探讨绝经后妇女体脂、瘦体重及血清脂联素(Adiponectin)、瘦素(Leptin)、抵抗素(Resistin)、Apelin、内脏脂肪素(Visfatin)与骨密度(Bone mineral density,BMD)的关系,为社区骨质疏松症防治提供有关实验依据。
方法采用酶免(ELISA)方法检测血清中Leptin、Adiponetin、Resistin、Visfatin、血清25-双羟维生素D(25-hydroxyvitamin D)、血清甲状旁腺激素(Intact parathyroid hormone,PTH)、胰岛素(Insulin)水平。采用化学发光法测定,血清中雌二醇(Estradiol)、总睾酮(Totaltestosterone,T)。采用HologicQDR-4500A型DXA仪测量总体、髋部总体、腰椎和前臂的骨密度。采用直线相关、偏相关分析Adiponectin、Leptin、Resistin、Apelin、Visfatin对BMD的影响。采用逐步多元线性回归法分别判定年龄、绝经年限、体重指数(Body mass index,BMI)、瘦体重、体脂、运动量、Adiponectin、Leptin、Resistin、Apelin、Visfatin、雌二醇(Estradiol)、睾酮(Testerone,T)、胰岛素(Insulin)、甲状旁腺激素(Parathyroid hormone,PTH)、25-双羟维生素D(25-hydroxyvitamin D)对BMD的影响。
结果直线相关分析显示:Adiponectin与总体BMD、腰椎BMD、髋部总体BMD、前臂BMD均呈负相关(r=-0.181,r=-0.208,r=-0.228,r=-0.203,p＜0.05),校正年龄和体脂后,相关性都依然存在(r=-0.131,r=-0.140,r=-0.149,r=-0.172,p＜0.05)。Leptin与髋部总体BMD、前臂BMD均呈正相关(r=0.162,r=0.210,p＜0.05);Leptin与总体BMD、腰椎BMD相关均无统计学意义;校正年龄和体脂后,Leptin与前臂BMD相关性存在(r=0.157,p＜0.05),而与髋部总体BMD相关无统计学意义。Resistin、Aplein、Visfatin与总体BMD、腰椎BMD、髋部总体BMD、前臂BMD相关均无统计学意义。逐步多元线性回归分析显示,绝经年限、瘦体重、Adiponectin是各部分BMD的主要影响因素。绝经后骨质疏松症妇女血清Adiponectin水平升高,而Leptin、Resistin、Apelin、Visfatin水平与对照组相比无差异。
结论Adiponectin与绝经后女性总体BMD、腰椎BMD、髋部总体BMD、前臂BMD负相关。Adiponectin是总体BMD、腰椎BMD、髋部总体BMD、前臂BMD的主要影响因素。绝经后骨质疏松症(OP)妇女血清Adiponectin水平升高,这指导我们在社区防治中,对检测到血清Adiponectin水平升高的绝经后妇女,应积极进行骨质疏松症的预防、监测。
第三章绝经后妇女脂肪因子血清脂联素、瘦素、抵抗素、Apelin及腹脂素与骨转换生化指标的关系研究
目的探索绝经后女性血清Adiponectin、Leptin、Resistin、Apelin、Visfatin与骨转换生化指标—血清骨特异性碱性磷酸酶(Bone alkalinephosphatase,BAP)、血清Ⅰ型胶原氨基末端肽(cross-linkedN-telopeptide of typeⅠcollagen,NTX)之间的关系。为疾病的机理研究及深入防治提供参考。
方法用ELISA测定287名40-80岁绝经后女性血清BAP、NTX。用直线相关、偏相关分析Adiponectin、Leptin、Resistin、Apelin、Visfatin与BAP、NTX的关系。
结果Adiponectin与BAP、NTX均呈正相关(r=0.202,r=0.215,p＜0.05),校正年龄和体脂后,相关性都依然存在(r=0.169,r=0.183,p＜0.05)。Leptin与BAP相关无统计学意义,与NTX呈负相关(r=-0.119,p＜0.05),校正年龄和体脂后,相关无统计学意义。Visfatin、Resistin、Aplein与BAP、NTX相关均无统计学意义。BAP、NTX与总体BMD、腰椎BMD、髋部总体BMD、前臂BMD均呈负相关,校正年龄和BMI后,相关性都依然存在。绝经后骨质疏松症妇女血清Adiponectin、BAP、NTX水平升高。
结论Adiponectin与骨吸收和骨形成生化指标相关,Adiponectin可能通过促进骨吸收大于骨形成,导致骨量丢失。绝经后骨质疏松症(OP)妇女血清Adiponectin、BAP、NTX水平升高。血清Adiponectin、BAP、NTX是患骨质疏松症患者的血清生化标志物。这提示我们,在社区骨质疏松症的防治中,对检测到血清Adiponectin、BAP、NTX升高的绝经后妇女应积极进行该症的预防、诊断与监测。
Chapter one Study on the present situation and the correlated factors of the community women with osteoporosis
Introduction: To realize the incidence rate and the correlated factors of the community women' osteoporosis during the period of premenopausal, perimenopausal and postmenopausal in Changsha. In order to find out the danger factor and the protection factor influencing on Bone Mineral Density (BMD) of the community women, and to provide support for preventing and curing osteoporosis in community.
Materials and Methods: To adopt the method of random samplings of the whole group, seperately collected samples from the community of Central South Specification for the engineering survey, Mawangdui community of Changsha, and the community of Xiangya Hospital. According to the content of the self-tabled questionnaire, the surveyor made home investigations to the community women with adopted standards at the age of 20-80. And accompanied the research subjects to the hospital, inspected their survey index such as Body Mass Index (BM), BMD and so on. Analyzed the incidence rate of the community women' osteoporosis during the period of premenopausal, perimenopausal and postmenopausal and its correlations with age, menopausal state. Made deep research on the correlated factors influencing on women with osteoporosis. Adopted Epidata3.0 to build data base, made statistical analysis of data by using software package of SPSS 13.0.
Results: The total incidence rate of the community women with osteoporosis in Changsha was 17.0%. Among which, the incidence rate of the community women with osteoporosis was 0.3% before 40 years old; separately, 5.4% at age that ranged from 40 to 49; 20.1% at age that ranged from 50 to 59; 44.8% at age that ranged from 60 to 69; 70.0% over 70 years old. The incidence rate of postmenopause women with osteoporosis was higher than that of premenopausal women with osteoporosis, the former was 22.9 times as much as the latter. The incidence rate of the community menopausal women with osteoporosis increased with the prolongation of age and since year menopause. The regression analysis of the unconditioned Logistics was used here, and found out that the old age(OR=1.832), late age of menarche(OR=2.589), post-menopausal (OR=1.507) , the prolongation of menopausal age (OR=2.168) , many times of parturition (OR= 1.449) were the danger factors of osteoporosis; high BMI (OR=0.514) and regular physical activity (OR=0.484) were the protection factors.
Conclusion: The incidence rate of the community women with osteoporosis increased with the prolongation of age and year since menopause; the incidence rate of postmenopause women with osteoporosis was highest, that of perimenopausal took second place, that of premenopausal was lowest. That the old age, late age of menarche, postmenopausal, the prolongation of year since menopause, many times of parturition were the danger factors of osteoporosis; high BMI and regular physical activity were the protection factors.
Chapter two Study on correlations between fat, the adipocytokine and bone mineral density in postmenopausal women
Introduction: Low Body Mass Index (BMI) was a danger factor of osteoporosis. Fat tissue of people with low BMI was cut down. The latest research showed that excreted factors of fat cells could regulate bone metabolism. Excreted factors of fat cells (called fat cells for short) mainly include adiponectin, leptin, resistin, apelin, visfatin. We make further step to explor the crrelations between body fat, lean body mass and adiponectin, leptin, resistin, Apelin, visfatin concentration and BMD; and so as to provide experimental support for preventing and curing osteoporosis in the community.
Materials and Methods: Serum concentrations of adiponectin, leptin, resistin, visfatin and serum levels of 25-hydroxyvitamin D, intact parathyroid hormone, insulin were measured with ELISA. Serum levels of estradiol, total testerone were detected by Chemical immunoassay. Bone mineral density (BMD) value were measured by using DXA at the total body, lumbar spine, total hip, and total forearm. Body composition including lean tissue mass and body fat mass were measured by DXA. The correlations between adiponectin, leptin, resistin, visfatin concentration and BMD, were made by using Pearson's correlation analysis and Partial correlation analysis. Multivariate linear stepwise regression analysis was performed to determine how much of the variance in BMD at various skeletal regions could be explained by age, year since menopause, BMI, lean mass, fat mass, physical activity, adiponectin, leptin, resistin, visfatin, estradiol, testerone , 25-hydroxyvitamin D, insulin, parathyroid hormone.
Results: Pearson's correlation analysis showed that: serum adiponectin levels were negatively related to BMD at total body, lumbar spine, total hip and total forearm (r=-0.181, r=-0.208, r=-0.228, r=-0.203, respectively, p<0.05). After adjusting age and fat mass, the correlation with BMD remained (r=-0.131, r=-0.140, r=-0.149, r=-0.172, respectively, p<0.05). Serum leptin levels were positively related to BMD at total hip and total forearm (r=0.162, r=0.210, respectively, p<0.05). After adjusting age and fat mass, the correlation with BMD at total forearm (r=0.157, p<0.05) existed, but the correlation with BMD at total hip disappeared. There were no correlations between serum resistin, apelin, visfatin and BMD at total body, lumbar spine, total hip and total forearm. The multivariate linear stepwise regression analysis showed that, year since menopause, lean mass, and adiponectin were chief predictors of BMD at total body, lumbar spine, total hip and total forearm. Moreover, serum adiponectin levels increased in postmenopausal women with osteoporosis; but there was no difference comparing serum levels of leptin, resistin, apelin and visfatin with control group.
Conclusion: Serum adiponectin levels were negatively related to BMD at total body, lumbar spine, total hip and total forearm. Adiponectin was the chief predictors of BMD at total body, lumbar spine, total hip and total forearm. Serum adiponectin levels increased in postmenopausal women with osteoporosis. It guided that, preventing and monitoring works in the community should be conducted activity in postmenopausal women with high serum adiponectin levels.
Chapter three Study on correlations between serum leptin, adiponectin, resistin, apelin, visfatin concentration and bone turn-over biochemical makers in postmenopausal women
Introduction: To explore the correlations between adiponectin, apelin, leptin, resistin, and Bone alkaline phosphatase (BAP), cross-linked N-telopeptide of type I collagen (NTX) in postmenopausal Chinese women. To provide reference for the mechanism study on osteoporosis, and for in-depth preventing and curing osteoporosis.
Materials and Methods: Serum bone alkaline phosphatase (BAP) and bone cross-linked N-telopeptides of typeⅠcollagen (NTX) of 287 postmenopausal women at the age of 40-80 were measured with ELISA. The correlations between adiponectin, leptin, resistin, apelin, visfatin concentration and BAP, NTX were determined by using Pearson's correlation analysis and Partial correlation analysis.
Results: Serum adiponectin levels were positively related to BAP and NTX (r=0.202, r=0.215, respectively, p<0.05). After adjusting age and fat mass, the correlation remained (r=0.169, r=0.183, respectively, p<0.05). Serum leptin levels were positively related to NXT, but not BAP (r=-0.119, p<0.05). After adjusting age and fat mass, the correlation disappeared. There were no correlations between serum visfatin, resistin, apelin and BAP, NTX. BAP and NTX were negatively related to BMD at total body, lumbar spine, total hip and total forearm. And after adjusting age and BMI, the correlation remained. The levels of serum adiponectin, BAP, NTX increased in postmenopausal women with osteoporosis.
Conclusion: Adiponectin were positively correlated with bone formation marker and bone resorption marker. It suggested that adiponectin may exert a negative effect on bone mass by promoting excessive bone resorption associated with bone loss in postmenopausal women. The levels of serum adiponectin, BAP, NTX increased in postmenopausal women. Serum adiponectin, BAP, NTX were serum biochemical marker of OP patient. It pointed out that, preventing, diagnosing and monitoring works in the community should be conducted activity in postmenopausal women with high levels of serum adiponectin, BAP, NTX.
目的了解长沙市社区未绝经、围绝经期、绝经后女性的骨质疏松发生率及相关因素,以期发现影响社区女性居民骨密度的危险因素和保护因素,为疾病社区防治提供依据。
方法采用整群随机抽样方法分别从中南勘察设计院生活社区、长沙马王堆社区、湘雅医院生活社区抽取样本,对其中常住户口年龄在20～80岁、符合纳入标准的社区女性调查员按自制调查表的调查内容入户实施调查,并陪同调查对象去医院进行体重指数、骨密度等调查指标的检查。分析社区未绝经,围绝经期及绝经后女性骨质疏松患病率及其与年龄、绝经状态的关系,深入研究影响女性骨质疏松症的相关因素。采用Epidata3.0建立数据库,应用SPSS13.0统计软件包进行数据的统计分析。
结果长沙市社区女性的骨质疏松症的总患病率为17.0%,40岁以下年龄段的患病率为0.3%。40岁～年龄段的患病率为5.4%;50岁～年龄段的患病率为20.1%;60岁～年龄段的患病率为44.8%;70岁～年龄段的患病率为70.0%。绝经后妇女骨质疏松患病率高于未绝经妇女骨质疏松患病率,前者为后者的22.9倍。社区绝经妇女骨质疏松的患病率随着年龄、绝经年限的延长而增加。采用非条件logistic回归分析发现骨质疏松症的危险因素为年龄大(OR=1.832)、初潮年龄晚(OR=2.589)、已绝经(OR=1.507)、绝经年限长(OR=2.168)、生产次数多(OR=1.449),保护因素为高体重指数(OR=0.514)和经常运动(OR=0.484)。
结论长沙社区女性骨质疏松症的患病率随年龄和绝经年限的增加相应增加;已绝经女性的骨质疏松症的患病率最高,围绝经期女性次之,未绝经女性最低。与骨质疏松症有关的危险因素为年龄大、初潮年龄晚、生产次数多、已绝经、绝经年限长,保护因素为高体重指数和经常运动。
第二章绝经后妇女肥胖相关指标、相关脂肪因子与骨密度的关系研究
目的低体重指数是骨质疏松症的危险因素,低体重指数人群脂肪组织减少。最近研究表明脂肪细胞分泌因子可调控骨代谢。脂肪细胞分泌因子(简称脂肪因子)主要有脂联素(Adiponectin)、瘦素(Leptin)、抵抗素(Resistin)、Apelin、内脏脂肪素(Visfatin)。我们进一步探讨绝经后妇女体脂、瘦体重及血清脂联素(Adiponectin)、瘦素(Leptin)、抵抗素(Resistin)、Apelin、内脏脂肪素(Visfatin)与骨密度(Bone mineral density,BMD)的关系,为社区骨质疏松症防治提供有关实验依据。
方法采用酶免(ELISA)方法检测血清中Leptin、Adiponetin、Resistin、Visfatin、血清25-双羟维生素D(25-hydroxyvitamin D)、血清甲状旁腺激素(Intact parathyroid hormone,PTH)、胰岛素(Insulin)水平。采用化学发光法测定,血清中雌二醇(Estradiol)、总睾酮(Totaltestosterone,T)。采用HologicQDR-4500A型DXA仪测量总体、髋部总体、腰椎和前臂的骨密度。采用直线相关、偏相关分析Adiponectin、Leptin、Resistin、Apelin、Visfatin对BMD的影响。采用逐步多元线性回归法分别判定年龄、绝经年限、体重指数(Body mass index,BMI)、瘦体重、体脂、运动量、Adiponectin、Leptin、Resistin、Apelin、Visfatin、雌二醇(Estradiol)、睾酮(Testerone,T)、胰岛素(Insulin)、甲状旁腺激素(Parathyroid hormone,PTH)、25-双羟维生素D(25-hydroxyvitamin D)对BMD的影响。
结果直线相关分析显示:Adiponectin与总体BMD、腰椎BMD、髋部总体BMD、前臂BMD均呈负相关(r=-0.181,r=-0.208,r=-0.228,r=-0.203,p＜0.05),校正年龄和体脂后,相关性都依然存在(r=-0.131,r=-0.140,r=-0.149,r=-0.172,p＜0.05)。Leptin与髋部总体BMD、前臂BMD均呈正相关(r=0.162,r=0.210,p＜0.05);Leptin与总体BMD、腰椎BMD相关均无统计学意义;校正年龄和体脂后,Leptin与前臂BMD相关性存在(r=0.157,p＜0.05),而与髋部总体BMD相关无统计学意义。Resistin、Aplein、Visfatin与总体BMD、腰椎BMD、髋部总体BMD、前臂BMD相关均无统计学意义。逐步多元线性回归分析显示,绝经年限、瘦体重、Adiponectin是各部分BMD的主要影响因素。绝经后骨质疏松症妇女血清Adiponectin水平升高,而Leptin、Resistin、Apelin、Visfatin水平与对照组相比无差异。
结论Adiponectin与绝经后女性总体BMD、腰椎BMD、髋部总体BMD、前臂BMD负相关。Adiponectin是总体BMD、腰椎BMD、髋部总体BMD、前臂BMD的主要影响因素。绝经后骨质疏松症(OP)妇女血清Adiponectin水平升高,这指导我们在社区防治中,对检测到血清Adiponectin水平升高的绝经后妇女,应积极进行骨质疏松症的预防、监测。
第三章绝经后妇女脂肪因子血清脂联素、瘦素、抵抗素、Apelin及腹脂素与骨转换生化指标的关系研究
目的探索绝经后女性血清Adiponectin、Leptin、Resistin、Apelin、Visfatin与骨转换生化指标—血清骨特异性碱性磷酸酶(Bone alkalinephosphatase,BAP)、血清Ⅰ型胶原氨基末端肽(cross-linkedN-telopeptide of typeⅠcollagen,NTX)之间的关系。为疾病的机理研究及深入防治提供参考。
方法用ELISA测定287名40-80岁绝经后女性血清BAP、NTX。用直线相关、偏相关分析Adiponectin、Leptin、Resistin、Apelin、Visfatin与BAP、NTX的关系。
结果Adiponectin与BAP、NTX均呈正相关(r=0.202,r=0.215,p＜0.05),校正年龄和体脂后,相关性都依然存在(r=0.169,r=0.183,p＜0.05)。Leptin与BAP相关无统计学意义,与NTX呈负相关(r=-0.119,p＜0.05),校正年龄和体脂后,相关无统计学意义。Visfatin、Resistin、Aplein与BAP、NTX相关均无统计学意义。BAP、NTX与总体BMD、腰椎BMD、髋部总体BMD、前臂BMD均呈负相关,校正年龄和BMI后,相关性都依然存在。绝经后骨质疏松症妇女血清Adiponectin、BAP、NTX水平升高。
结论Adiponectin与骨吸收和骨形成生化指标相关,Adiponectin可能通过促进骨吸收大于骨形成,导致骨量丢失。绝经后骨质疏松症(OP)妇女血清Adiponectin、BAP、NTX水平升高。血清Adiponectin、BAP、NTX是患骨质疏松症患者的血清生化标志物。这提示我们,在社区骨质疏松症的防治中,对检测到血清Adiponectin、BAP、NTX升高的绝经后妇女应积极进行该症的预防、诊断与监测。
Chapter one Study on the present situation and the correlated factors of the community women with osteoporosis
Introduction: To realize the incidence rate and the correlated factors of the community women' osteoporosis during the period of premenopausal, perimenopausal and postmenopausal in Changsha. In order to find out the danger factor and the protection factor influencing on Bone Mineral Density (BMD) of the community women, and to provide support for preventing and curing osteoporosis in community.
Materials and Methods: To adopt the method of random samplings of the whole group, seperately collected samples from the community of Central South Specification for the engineering survey, Mawangdui community of Changsha, and the community of Xiangya Hospital. According to the content of the self-tabled questionnaire, the surveyor made home investigations to the community women with adopted standards at the age of 20-80. And accompanied the research subjects to the hospital, inspected their survey index such as Body Mass Index (BM), BMD and so on. Analyzed the incidence rate of the community women' osteoporosis during the period of premenopausal, perimenopausal and postmenopausal and its correlations with age, menopausal state. Made deep research on the correlated factors influencing on women with osteoporosis. Adopted Epidata3.0 to build data base, made statistical analysis of data by using software package of SPSS 13.0.
Results: The total incidence rate of the community women with osteoporosis in Changsha was 17.0%. Among which, the incidence rate of the community women with osteoporosis was 0.3% before 40 years old; separately, 5.4% at age that ranged from 40 to 49; 20.1% at age that ranged from 50 to 59; 44.8% at age that ranged from 60 to 69; 70.0% over 70 years old. The incidence rate of postmenopause women with osteoporosis was higher than that of premenopausal women with osteoporosis, the former was 22.9 times as much as the latter. The incidence rate of the community menopausal women with osteoporosis increased with the prolongation of age and since year menopause. The regression analysis of the unconditioned Logistics was used here, and found out that the old age(OR=1.832), late age of menarche(OR=2.589), post-menopausal (OR=1.507) , the prolongation of menopausal age (OR=2.168) , many times of parturition (OR= 1.449) were the danger factors of osteoporosis; high BMI (OR=0.514) and regular physical activity (OR=0.484) were the protection factors.
Conclusion: The incidence rate of the community women with osteoporosis increased with the prolongation of age and year since menopause; the incidence rate of postmenopause women with osteoporosis was highest, that of perimenopausal took second place, that of premenopausal was lowest. That the old age, late age of menarche, postmenopausal, the prolongation of year since menopause, many times of parturition were the danger factors of osteoporosis; high BMI and regular physical activity were the protection factors.
Chapter two Study on correlations between fat, the adipocytokine and bone mineral density in postmenopausal women
Introduction: Low Body Mass Index (BMI) was a danger factor of osteoporosis. Fat tissue of people with low BMI was cut down. The latest research showed that excreted factors of fat cells could regulate bone metabolism. Excreted factors of fat cells (called fat cells for short) mainly include adiponectin, leptin, resistin, apelin, visfatin. We make further step to explor the crrelations between body fat, lean body mass and adiponectin, leptin, resistin, Apelin, visfatin concentration and BMD; and so as to provide experimental support for preventing and curing osteoporosis in the community.
Materials and Methods: Serum concentrations of adiponectin, leptin, resistin, visfatin and serum levels of 25-hydroxyvitamin D, intact parathyroid hormone, insulin were measured with ELISA. Serum levels of estradiol, total testerone were detected by Chemical immunoassay. Bone mineral density (BMD) value were measured by using DXA at the total body, lumbar spine, total hip, and total forearm. Body composition including lean tissue mass and body fat mass were measured by DXA. The correlations between adiponectin, leptin, resistin, visfatin concentration and BMD, were made by using Pearson's correlation analysis and Partial correlation analysis. Multivariate linear stepwise regression analysis was performed to determine how much of the variance in BMD at various skeletal regions could be explained by age, year since menopause, BMI, lean mass, fat mass, physical activity, adiponectin, leptin, resistin, visfatin, estradiol, testerone , 25-hydroxyvitamin D, insulin, parathyroid hormone.
Results: Pearson's correlation analysis showed that: serum adiponectin levels were negatively related to BMD at total body, lumbar spine, total hip and total forearm (r=-0.181, r=-0.208, r=-0.228, r=-0.203, respectively, p<0.05). After adjusting age and fat mass, the correlation with BMD remained (r=-0.131, r=-0.140, r=-0.149, r=-0.172, respectively, p<0.05). Serum leptin levels were positively related to BMD at total hip and total forearm (r=0.162, r=0.210, respectively, p<0.05). After adjusting age and fat mass, the correlation with BMD at total forearm (r=0.157, p<0.05) existed, but the correlation with BMD at total hip disappeared. There were no correlations between serum resistin, apelin, visfatin and BMD at total body, lumbar spine, total hip and total forearm. The multivariate linear stepwise regression analysis showed that, year since menopause, lean mass, and adiponectin were chief predictors of BMD at total body, lumbar spine, total hip and total forearm. Moreover, serum adiponectin levels increased in postmenopausal women with osteoporosis; but there was no difference comparing serum levels of leptin, resistin, apelin and visfatin with control group.
Conclusion: Serum adiponectin levels were negatively related to BMD at total body, lumbar spine, total hip and total forearm. Adiponectin was the chief predictors of BMD at total body, lumbar spine, total hip and total forearm. Serum adiponectin levels increased in postmenopausal women with osteoporosis. It guided that, preventing and monitoring works in the community should be conducted activity in postmenopausal women with high serum adiponectin levels.
Chapter three Study on correlations between serum leptin, adiponectin, resistin, apelin, visfatin concentration and bone turn-over biochemical makers in postmenopausal women
Introduction: To explore the correlations between adiponectin, apelin, leptin, resistin, and Bone alkaline phosphatase (BAP), cross-linked N-telopeptide of type I collagen (NTX) in postmenopausal Chinese women. To provide reference for the mechanism study on osteoporosis, and for in-depth preventing and curing osteoporosis.
Materials and Methods: Serum bone alkaline phosphatase (BAP) and bone cross-linked N-telopeptides of typeⅠcollagen (NTX) of 287 postmenopausal women at the age of 40-80 were measured with ELISA. The correlations between adiponectin, leptin, resistin, apelin, visfatin concentration and BAP, NTX were determined by using Pearson's correlation analysis and Partial correlation analysis.
Results: Serum adiponectin levels were positively related to BAP and NTX (r=0.202, r=0.215, respectively, p<0.05). After adjusting age and fat mass, the correlation remained (r=0.169, r=0.183, respectively, p<0.05). Serum leptin levels were positively related to NXT, but not BAP (r=-0.119, p<0.05). After adjusting age and fat mass, the correlation disappeared. There were no correlations between serum visfatin, resistin, apelin and BAP, NTX. BAP and NTX were negatively related to BMD at total body, lumbar spine, total hip and total forearm. And after adjusting age and BMI, the correlation remained. The levels of serum adiponectin, BAP, NTX increased in postmenopausal women with osteoporosis.
Conclusion: Adiponectin were positively correlated with bone formation marker and bone resorption marker. It suggested that adiponectin may exert a negative effect on bone mass by promoting excessive bone resorption associated with bone loss in postmenopausal women. The levels of serum adiponectin, BAP, NTX increased in postmenopausal women. Serum adiponectin, BAP, NTX were serum biochemical marker of OP patient. It pointed out that, preventing, diagnosing and monitoring works in the community should be conducted activity in postmenopausal women with high levels of serum adiponectin, BAP, NTX.
引文
[1] Kao PC, P'eng FK.How to reduce the risk factors of osteoporosis in Asia. Chung Hua I Hsueh Tsa Chih (Taipei) , 1995,55 (3) : 209 -13.
[2] Hla MM, Davis JW, Ross PD, et al. A multicenter study of the influence of fat and lean mass on bone mineral content: evidence for differences in their relative influence at major fracture sites. Early Postmenopausal Intervention Cohort (EPIC) Study Group. Am J Clin Nutr, 1996,64:354-60.
[3] Lindsay R, Cosman F, Herrington BS, et al. Bone mass and body composition in normal women. J Bone Miner Res, 1992,7: 55-62.
[4] Tcheraof A, Despres JP, Belanger A, et al. Reduced testosterone and adrenal C19 steroid levels in obese men. Metabolism, 1995,44: 513-9.
[5] Corbould AM, Bawden MJ, Lavranos TC, et al. The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women. Int J Obes Relat Metab Disord, 2002,26:165-75.
[6] Khosla S, Melton LJ 3rd, Atkinson EJ, et al. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women:a key role for bioavailable estrogen. J Clin Endocrinol Metab, 1998, 83:2266-74.
[7] Reid IR, Evans MC, Cooper GJ, et al. Circulating insulin levels are related to bone density in normal postmenopausal women. Am J Physiol, 1993, 265:E655-9.
[8] Barrett-Connor E, Kritz-Silverstein D. Does hyperinsulinemia preserve bone? Diabetes Care, 1996,19:1388-92.
[9] Maeda K, Okubo K, Shimomura I, et al.cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1) . Biochem Biophys Res Commun, 1996,221: 286-9.
[10] Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005, 309: 99-109.
[11] Berner HS, Lyngstadaas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone-forming cells.Bone,2004,35:842-9.
[12]Kershaw EE,Flier JS.Adipose tissue as an endocrine organ.J Clin Enocri Metab,2004,89:2548-56.
[13]Matsubara M,Maruoka S,Katayose S.Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women.Eur J Endocrinol,2002,147:173-80.
[14]Luo XH,Guo L J,Xie H,et al.Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway.J Bone Miner Res,2006,21:1648-56.
[15]Shinoda Y,Yarnaguchi M,Ogata N,et al.Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.J Cell Biochem.2006,99:196-208.
[16]Zhang Y,Proenca R,Maffei M,et al.Positional cloning of the mouse obese gene and its human homologue.Nature,1994,372:425-32.
[17]Thomas T,Burguera B,Melton LJ 3rd,et al.Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women.Metabolism,2000,49:1278-84.
[18]Considine RV,Sinha MK,Heiman ML,et al.Serum immunoreactive-leptin concentrations in normal-weight and obese humans.N Engl J Med,1996,334:292-5.
[19]Wauters M,Considine RV,Van Gaal LF.Human leptin:from an adipocyte hormone to an endocrine mediator.Eur J Endocrinol,2000,143:293-311.
[20]Reseland JE,Syversen U,Bakke I,et al.Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization,J Bone Miner Res.2001,16:1426-33.
[21]Thomas T,Gori F,Khosla S,et al.Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes.Endocrinology,1999,140:1630-8.
[22]Ducy P,Amling M,Takeda S,et al.Leptin inhibits bone formation through a hypothalamic relay:a central control of bone mass.Cell,2000,100:197-207.
[23]Steppan CM,Bailey ST,Bhat S,et al.The hormone resistin links obesity to diabetes.Nature,2001,409:307-12.
[24]Patel L,Buckels AC,Kinghorn IJ,et al.Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators.Biochem Biophys Res Commun, 2003,300:472-6.
[25] Lecka-Czernik B, Moerman EJ, Grant DF, et al. Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology, 2002,143:2376-84.
[26] Oh KW, Lee WY, Rhee EJ, et al.The relationship between serum resistin, leptin,adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clin Endocrinol (Oxf),2005,63:131-8.
[27] Boucher J, Masri B, Daviaud D, et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology, 2005,146:1764-71.
[28] O'Dowd BF, Heiber M, Chan A, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene,1993,136: 355-60.
[29] Tatemoto K, Hosoya M, Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun, 1998,251:471-6.
[30] Medhurst AD, Jennings CA, Robbins MJ. Pharmacological and immunohisto-chemical characterization of the APJ receptor and its endogenous ligand apelin.J Neurochem, 2003,84:1162-1172.
[31] Charles CJ. Putative role for apelin in pressure/volume homeostasis and cardiovascular disease. Cardiovasc Hematol Agents Med Chem, 2007,5:1-10.
[32] Beltowski J. Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? Med Sci Monit, 2006,12: RA112-9.
[33] Lee DK, George SR, O'Dowd BF. Unravelling the roles of the apelin system:prospective therapeutic applications in heart failure and obesity. Trends Pharmacol Sci, 2006,27: 190-4.
[34] Kleinz MJ, Davenport AP. Emerging roles of apelin in biology and medicine.Pharmacol Ther, 2005,107: 198-211.
[35] Wang G, Anini Y, Wei W, et al. Apelin, a new enteric peptide: localization in the gastrointestinal tract, ontogeny, and stimulation of gastric cell proliferation and of cholecystokinin secretion. Endocrinology, 2004,145: 1342-1348.
[36] Tang SY, Xie H, Yuan LQ, et al. Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways. Peptides, 2007, 28: 708-18.
[37]Xie H,Tang SY,Cui RR,et al.Apelin and its receptor are expressed in human osteoblasts.Regul Pept,2006,134:118-25.
[38]Xie H,Yuan LQ,Luo XH,et al.Apelin suppresses apoptosis of human osteoblasts.Apoptosis,2007,12:247-54.
[39]Fukuhara A,Matsuda M,Nishizawa M,et al.Visfatin:a protein secreted by visceral fat that mimics the effects of insulin.Science,2005,307:426-30.
[40]Berndt J,Kloting N,Kralisch S,et al.Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.Diabetes,2005,54:2911-6.
[41]Chen MP,Chung FM,Chang DM,et al.Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.J Clin Endocrinol Metab,2006,91:295-9.
[42]Haider DG,Schindler K,Schaller G,et al.Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding.J Clin Endocrinol Metab,2006,91:1578-81.
[43]Xie H,Tang SY,Luo XH,et al.Insulin-like effects of visfatin on human osteoblasts.Calcif Tissue Int,2007,8:201-10.
[44]李宁华,区品中,朱汉民,等.中国部分地区中老年人群原发性骨质疏松症患病率研究中华骨科杂志,2001,21(5):275-278.
[45]廖二元,伍贤平,邓小戈,等.对中国长沙地区女性骨密度情况的调查.中华内分泌代谢杂志,2000,16:203-207.
[46]孙振球.医学统计学.人民卫生出版社,2002:579.
[47]Wu XP,Liao EY,Zhang H,et al.Establishment of BMD reference plots and determination of peak BMD at multiple skeletal regions in mainland Chinese women and the diagnosis of osteoporosis.Osteoporosis Int,2004,15:71-9.
[48]Liao EY,Wu XP,Deng XG,et al.Aged-related bone mineral density,accumulated bone loss rate and prevalence of osteoporosis at multiple skeletal sites in Chinese women.Osteoporosis Int,2002,13:669-76.
[49]Kanis JA,Melton LJ 3rd,Christiansen C,et al.The diagnosis of osteoporosis.Journal of Bone and Mineral Research,1994,9:1137-41.
[50]王志文,马锦富,杨定悼等.成都地区中老年人群骨密度调查.中国骨质疏松杂志,2000,6(1):40-43. 率的调查.中国骨质疏松杂志,2002,8(4):314-318.
[52]颜晓东,王风,黄忠等.广西南宁地区汉壮族人群骨密度及骨质疏松患病率研究.中国骨质疏松杂志,2003,9(3):268-270.
[53]NIH.Consensus Development panel on osteoporosis.JAMA,2001,85:785-95.
[54]Lau EM,Lee JK,SuriwongpaisalP,et al.T he incidence of hipfracturein four Asianeountries:the Asian Osteoporosis Study(AOS).Osteoporosis Int,2001,12:239-43.
[55]Wasnich RD.Epidemiology of osteoporosis in the United States of America.Osteoporosis Int,1997,7:68-72.
[56]朱国英,王洪复,王莉华,等.绝经后妇女骨质疏松性骨折易发因素的流行病学研究.中国骨质疏松杂志,2004,10(2):172-74.
[57]Zhang m,Shimmura t,Bi lf,et al.Bone mass and lifestyle related factors:a comparative study between Japanese and Inner Mongolian young premenopausal women.Osteoporos Int,2004,15(7):547-51.
[58]Takanobu A,Fumiko M,Toshiko T,et al.Risk of irregular menstrual cycles and low peak bone mass during early a ulthood associated with age at menarche Pediatircs Int,2001,43(5):483-8.
[59]刘继洪,杨延斌,曹海伟,等,成年人骨密度、骨量、体重、年龄、身高、脂肪含量相互关系的研究.实用医学杂志,2002,18(2):146-7.
[60]王莉华,王伟华,王洪复,等.体重和身高对绝经后妇女骨密度值的影响.中华实用医学,2002,4(13):41-3.
[61]Douglas CB,Warren SB,Jane MC,et al.Factors associated with appendicular bone mass in older women.Ann Intent Med,1993,118(9):657-65.
[62]Angela JS.An overview of osteoporosis.Altenr Ther Health Med,2004,10(2):26-34.
[63]Guyen TN,Center JR,Eisman JA.Osteoporosisin elderly men and women:effects of dietary Calcium,physicala etivity,and body mass index.J Bone Miner Res,2000,15(2):322-31.
[64]Susan JW,Hassanail V,Adam BJ,et al.Factors that affect bone mineral accrual in the adolescent growth spurt.J Nutrion,2004,134(3):696-700.
[65]Saija K,Pekka K,Heidi H,et al.Good maintenance of exercise-induced bone Gain with decreased training of female tennis and Squashp layers:prospective 5-year follow-up study of young and old sarters and controls.J Bone Miner Res,2001,16(2):195-201.
[66]朱敏嘉,王风,颜晓东,等.中老年妇女骨质疏松发病危险因素分析.中国老年学杂志,2002,22(4):249-50.
[67]O'Neill TW,Silman AJ,Naves Diaz M.Influence of hormonal and reProductiv factors on the risk of vertebarl defomrity in European woman.European Vertebra of Osteoporosis Study Group.Osteoporosis Int,1997,7(1):72-8.
[68]Cure-Cure C,Cure-Ramirez P,Teran E,et al.Bone-masspeak in multiparity and reduce risk of bone-fractures in menopause.Int J Gynaecol Obstet,2002,76(3):285-91.
[69]李卫敏.骨折、钙和现代饮食.国外医学医学地理分册,2002;23(2).
[70]Hla MM,Davis JW,Ross PD,et al.A multicenter study of the influence of fat and lean mass on bone mineral content:evidence for differences in their relative influence at major fracture sites.Early Postmenopausal Intervention Cohort (EPIC) Study Group.Am J Clin Nutr,1996,64:354-60.
[71]Lindsay R,Cosman F,Herrington BS,et al.Bone mass and body composition in normal women.J Bone Miner Res,1992,7:55-62.
[72]Tchernof A,Despres JP,Belanger A,et al.Reduced testosterone and adrenal C19 steroid levels in obese men.Metabolism,1995,44:513-9.
[73]Corbould AM,Bawden MJ,Lavranos TC,et al.The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women.Int J Obes Relat Metab Disord,2002,26:165-75.
[74]Khosla S,Melton LJ 3rd,Atkinson EJ,et al.Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women:a key role for bioavailable estrogen.J Clin Endocrinol Metab,1998,83:2266-74.
[75]Reid IR,Evans MC,Cooper GJ,et al.Circulating insulin levels are related to bone density in normal postmenopausal women.Am J Physiol,1993,265:E655-9.
[76]Barrett-Connor E,Kritz-Silverstein D.Does hyperinsulinemia preserve bone?Diabetes Care,1996,19:1388-92.
[77]Maeda K,Okubo K,Shimomura I,et al.cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1) . Biochem Biophys Res Commun, 1996,221: 286-9.
[78] Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Enocri Metab, 2004, 89:2548-56.
[79] Matsubara M, Maruoka S, Katayose S. Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol, 2002,147:173-80.
[80] Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005,309: 99-109.
[81] Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res, 2006,21:1648-56.
[82] Shinoda Y, Yamaguchi M, Ogata N, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem, 2006,99:196-208.
[83] Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994,372:425-32.
[84] Thomas T, Burguera B, Melton LJ 3rd, et al. Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women.Metabolism, 2000,49:1278-84.
[85] Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med, 1996, 334:292-5.
[86] Wauters M, Considine RV, Van Gaal LF. Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol, 2000,143: 293-311.
[87] Reseland JE, Syversen U, Bakke I, et al. Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization.J Bone Miner Res, 2001,16: 1426-33.
[88] Thomas T, Gori F, Khosla S, et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology, 1999,140: 1630-8.
[89] Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell, 2000,100:197-207.
[90] Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature, 2001,409: 307-12.
[91] Patel L, Buckels AC, Kinghorn IJ, et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun, 2003,300:472-6.
[92] Lecka-Czernik B, Moerman EJ, Grant DF, et al. Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology, 2002,143:2376-84.
[93] Oh KW, Lee WY, Rhee EJ, et al. The relationship between serum resistin,leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men.Clin Endocrinol (Oxf) , 2005, 63:131-8.
[94] Boucher J, Masri B, Daviaud D, et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology, 2005,146:1764-71.
[95] O'Dowd BF, Heiber M, Chan A, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene,1993,136: 355-60.
[96] Tatemoto K, Hosoya M, Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun, 1998,251:471-6.
[97] Medhurst AD, Jennings CA, Robbins MJ. Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin. J Neurochem, 2003, 84:1162-1172.
[98] Charles CJ. Putative role for apelin in pressure/volume homeostasis and cardiovascular disease. Cardiovasc Hematol Agents Med Chem, 2007,5:1-10.
[99] Beltowski J. Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? Med Sci Monit, 2006,12: RA112-9.
[100] Tang SY, Xie H, Yuan LQ, et al. Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways. Peptides, 2007,28: 708-18.
[101] Xie H, Tang SY, Cui RR, et al. Apelin and its receptor are expressed in human osteoblasts. Regul Pept, 2006,134 (2-3) :118-25.
[102] Xie H, Yuan LQ, Luo XH, et al. Apelin suppresses apoptosis of human osteoblasts.Apoptosis,2007,12:247-54.
[103]Fukuhara A,Matsuda M,Nishizawa M,et al.Visfatin:a protein secreted by visceral fat that mimics the effects of insulin.Science,2005,307:426-30.
[104]Berndt J,Kloting N,Kralisch S,et al.Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.Diabetes,2005,54:2911-6.
[105]Chen MP,Chung FM,Chang DM,et al.Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.J Clin Endocrinol Metab,2006,91:295-9.
[106]Xie H,Tang SY,Luo XH,et al.Insulin-like effects of visfatin on human osteoblasts.Calcif Tissue Int,2007,8:201-10.
[107]Lim S,Joung H,Shin CS,et al.Body composition changes with age have gender-specific impacts on bone mineral density.Bone,2004,35:792-8.
[108]Pongchaiyakul C,Nguyen TV,Kosulwat V,et al.Contribution of lean tissue mass to the urban-rural difference in bone mineral density.Osteoporos Int,2005,16:1761-8.
[109]Wang MC,Bachrach LK,Van Loan M,et al.The relative contributions of lean tissue mass and fat mass to bone density in young women.Bone,2005,37:474-81.
[110]Li S,Wagner R,Holm K,et al.Relationship between soft tissue body composition and bone mass in perimenopausal women.Maturitas,2004,47:99-105.
[111]Van Langendonck L,Claessens AL,Lefewe J,et al.Association between bone mineral density(DXA),body structure,and body composition in middle-aged men.Am J Hum Biol,2002,14:735-42.
[112]Capozza RF,Cointry GR,Cure-Ramirez P,et al.A DXA study of muscle-bone relationships in the whole body and limbs of 2512 normal men and pre- and post-menopausal women.Bone,2004,35:283-95.
[113]Kontogianni MD,Dafni UG,Routsias JG,et al.Blood leptin and adiponectin as possible mediators of the relation between fat mass and BMD in perimenopausal women.J Bone Miner Res,2004,19:546-51.
[114]Huang KC,Cheng WC,Yen RF,et al.Lack of independent relationship between plasma adiponectin,leptin levels and bone density in nondiabetic female adolescents.Clin Endocrinol(Oxf),2004,61:204-8.
[115] Zhao LJ, Liu YJ, Liu PY, et al. Relationship of obesity with osteoporosis. J Clin Endocrinol Metab, 2007,92:1640-6.
[116] Ijuin M, Douchi T, Matsuo T, et al. Difference in the effects of body composition on bone mineral density between pre- and postmenopausal women.Maturitas, 2002,43 (4) :239-44.
[117] Douchi T, Kuwahata R, Matsuo T, et al. Relative contribution of lean and fat mass component to bone mineral density in males. J Bone Miner Metab, 2003,21:17-21.
[118] Blain H, Carriere I, Favier F, Jeandel C, Papoz L; EPIDOS Study Group. Body weight change since menopause and percentage body fat mass are predictors of subsequent bone mineral density change of the proximal femur in women aged 75 years and older: results of a 5 year prospective study. Calcif Tissue Int, 2004,75:32-9.
[119] Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature, 2003,423: 762-9.
[120] Wallis GA, Rash B, Sykes B,et al. Mutations within the gene encoding the alpha 1 (X) chain of type X collagen (COL10A1) cause metaphyseal chondrodysplasia type Schmid but not several other forms of metaphyseal chondrodysplasia. J Med Genet, 1996,33:450-7.
[121] Ouchi N, Kihara S, Arita Y, et al.Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation, 2000,102:1296-301.
[122] Yokota T, Meka CS, Medina KL, et al. Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins. J Clin Invest, 2002,109:1303-10.
[123] Bemer HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA,Syversen U, Reseland JE. Adiponectin and its receptors are expressed in bone-forming cells.Bone, 2004,35: 842-9.
[124] Oshima K, Nampei A, Matsuda M,et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun, 2005, 331: 520-6.
[125] Lenchik L, Register TC, Hsu FC, et al. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone, 2003, 33: 646-51.
[126]J(u|¨)rim(a|¨)e J,Rembel K,J(u|¨)rim(a|¨)e T,et al.Adiponectin is associated with bone mineral density in perimenopausal women.Horm Metab Res,2005,37:297-302.
[127]J(u|¨)rim(a|¨)e J,J(u|¨)rim(a|¨)e T.Plasma adiponectin concentration in healthy pre- and postmenopausal women:relationship with body composition,bone mineral and metabolic variables.Am J Physiol Endocrinol Metab,2007,293:E42-7.
[128]Misra M,Miller KK,Cord J,wt al.Relationships between Serum Adipokines,Insulin Levels and Bone Density in Girls with Anorexia Nervosa.J Clin Endocrin Metab,2007,92:2046-52.
[129]Richards JB,Valdes AM,et al.Serum Adiponectin and Bone Mineral Density in Women.J Clin Endocrin Metab,2007,92:1517-23.
[130]Aubin JE,Bonnelye E.Osteoprotegerin and its ligand:a new paradigm for regulation of osteoclastogenesis and bone resorption.Osteoporos Int,2000,11:905-13.
[131]Suda T,Takahashi N,Udagawa N,et al.Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families.Endocr Rev,1999,20:345-57.
[132]Takahashi N,Udagawa N,Suda T.A new member of tumor necrosis factor ligand family,ODF/OPGL/TRANCE/RANKL,regulate sosteoclast differentiation and function.Biochem Biophys Res Commun,1999,256:449-55.
[133]Gordeladze JO,Drevon CA,Syversen U,et al.Leptin stimulates human osteoblastic cell proliferation,de novo collagen synthesis,and mineralization:Impact on differentiation markers,apoptosis,and osteoclastic signaling.J Cell Biochem,2002,85:825-36.
[134]Steppan CM,Crawford DT,Chidsey-Frink KL,et al.Leptin is a potent stimulator of bone growth in ob/ob mice.Regul Pept,2000,92:73-8.
[135]Duty P,Schinke T,Karsenty G.The osteoblast:a sophisticated fibroblast under central surveillance.Science,2000,289:1501-4.
[136]Chanprasertyothin S,Piaseu N,Chailurkit L,et al.Association of circulating leptin with bone mineral density in males and females.J Med Assoc Thai,2005,88:655-9.
[137]Sato M,Takeda N,Sarui H,Takami R,et al.Association between serum leptin concentrations and bone mineral density,and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab, 2001, 86: 5273-6.
[138] Pasco JA, Henry MJ, Kotowicz MA, et al. Serum leptin levels are associated with bone mass in nonobese women.J Clin Endocrinol Metab, 2001, 86:1884-7.
[139] Ruhl CE, Everhart JE. Relationship of serum leptin concentration with bone mineral density in the United States population. J Bone Miner Res, 2002, 17:1896-903.
[140] Wosje KS, Binkley TL, Kalkwarf HJ, et al. Relationships between bone mass and circulating leptin concentrations in Hutterites. Bone, 2004,34: 1017-22.
[141] Thomas T, Burguera B, Melton LJ 3rd, et al. Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone, 2001,29: 114-20.
[142] Zhong N, Wu XP, Xu ZR, et al. Relationship of serum leptin with age, body weight, body mass index, and bone mineral density in healthy mainland Chinese women.Clin Chim Acta, 2005, 351: 161-8.
[143] Sinha MK, Ohannesian JP, Heiman ML, et al. Nocturnal rise of leptin in lean,obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest, 1996,97:1344-7.
[144] Nagaev I , Smith U. Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. BiochemBiophys Res Commun,2001,285: 561-4.
[145] Savage DB, Sewter CP, Klenk ES, et al. Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes, 2001, 50:2199-202.
[146] Schinke T, Haberland M, Jamshidi A, et al. Cloning and functional characterization of resistin-like molecule gamma. Biochem Biophys Res Commun, 2004,314: 356-62.
[147] Gonnelli S, Cepollaro C, Gennari L, Montagnani A, et al. Quantitative ultrasound and dual-energy X-ray absorptiometry in the prediction of fragility fracture in men. Osteoporos Int, 2005,16: 963-8.
[148] Broe KE, Hannan MT, Kiely DK, et al. Predicting fractures using bone mineral density: a prospective study of long-term care residents. Osteoporos Int, 2000,11:765-71.
[149]单鹏飞,伍贤平,廖二元等.女性骨代谢转换生化标物各骨密度随年龄变化及其相互关系.中华老年医学杂志,2005,24:431-4.
[150]Iki M,Akiba T,Matsumoto T,Nishino H,Kagamimori S,Kagawa Y,Yoneshima H;JPOS Study Group.Reference database of biochemical markers of bone turnover for the Japanese female population.Japanese Population-based Osteoporosis(JPOS) Study.Osteoporos Int,2004,15:981-91.
[151]Gomes B Jr,Ardakani S,Ju J,et al.Monoclonal antibody assay for measuring bone alkaline phosphatase activity in serum.Clin Chem,1995,41:1560-66.
[152]Hanson DA,Weis MA,Bollen AM,et al.A specific immunoassay for monitoring human bone resorption:quantitation of type Ⅰ collagen croo-linked N-telopeptides in urine.J Bone Miner Res,1992,7:1251-8.
[153]Clemens JD,Herrick MV,Singer FR,et al.Evidence that serum NTx (collagen-type I N-telopeptides) can act as an immunochemical marker of bone resorption.Clin Chem,1997,43:2058-63.
[154]杨伟民.骨代谢生化指标与骨质疏松症.中国骨质疏松杂志,2004,10:118-9.
[155]Blain H,Vuillemin A,Guillemin F,et al.Serum leptin level is a predictor of bone mineral density in postmenopausal women.J Clin Endocrinol Metab,2002,87:1030-5.
[156]Sato M,Takeda N,Sarui H,et al.Association between serum leptin concentrations and bone mineral density,and biochemical markers of bone turnover in adult men.J Clin Endocrinol Metab,2001,86:5273-6.
[157]Scariano JK,Garry PJ,Montoya GD,et al.Serum leptin levels,bone mineral density and osteoblast alkaline phosphatase activity in elderly men and women.Mech Ageing Dev,2003,124:281-6.
[158]Tamura T,Yoneda M,Yamane K,et al.Serum leptin and adiponectin are positively associated with bone mineral density at the distal radius in patients with type 2 diabetes mellitus.Metabolism,2007,56:623-8.
[159]Luo XH,Guo LJ,Shan PF,et al.Relationship of circulating MMP-2,MMP-1,and TIMP-1 levels with bone biochemical markers and bone mineral density in postmenopausal Chinese women.Osteoporos Int,2006,17:521-6.
[160]Richards JB,Valdes AM,et al.Serum Adiponectin and Bone Mineral Density in Women.J Clin Endocrin Metab,2007,92:1517-23.
[161] J(?)rim(?)e J, Rembel K, J(?)rim(?)e T, et al. Adiponectin is associated with bone mineral density in perimenopausal women. Horm Metab Res, 2005, 37:297-302.
[162] Misra M, Miller KK, Cord J, wt al. Relationships between Serum Adipokines,Insulin Levels and Bone Density in Girls with Anorexia Nervosa. J Clin Endocrin Metab, 2007,92:2046-52.
[163] Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res, 2006,21:1648-56.
[164] Aubin JE, Bonnelye E. Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. Osteoporos Int, 2000, 11:905-13.
[165] Suda T, Takahashi N, Udagawa N, et al. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev, 1999,20: 345-57.
[166] Takahashi N, Udagawa N, Suda T. A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function. Biochem Biophys Res Commun, 1999, 256:449-55.
[167] Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005,309: 99-109.
[168] Minisola S, Pacitti MT, Ombricolo E, et al. Bone turnover and its relationship with bone mineral density in pre- and postmenopausal women with or without fractures. Maturitas, 1998,29:265-70.
[169] Khosla S, Melton LJ 3rd, Atkinson EJ, et al. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women:a key role for bioavailable estrogen. J Clin Endocrinol Metab, 1998, 83:2266-74.
[170] Szulc P, Garnero P, Munoz F, et al. Cross-sectional evaluation of bone metabolism in men. J Bone Miner Res, 2001,16: 1642-50.
[171] Khosla S, Melton LJ III, Atkinson EJ, et al. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women:a key role for bioavailable estrogen. J Clin Endocrinol Metab, 1998, 83: 2266-74.
[172] Goemaere S, Van Pottelbergh I, Zmierczak H, et al. Inverse association between bone turnover rate and bone mineral density in community-dwelling men ＞70 years of age: no major role of sex steroid status. Bone, 2001,29:286-91.
[173] Tsai KS, Pan WH, Hsu SHJ, et al. Sexual differences in bone markers and bone mineral density of normal Chinese. Calcif Tissue Int, 1996,59:454-60.
[174] Scopacasa F, Wishart JM, Need AG, et al. Bone Density and Bone-Related Biochemical Variables in Normal Men A Longitudinal Study. Gerontol A Biol Sci Med Sci, 2002,57: M385-91.
[1]廖二元,伍贤平,邓小戈,等.对中国长沙地区女性骨密度情况的调查.中华内分泌代谢杂志,2000,16:203-7.
[2]Cooper C,Campion G,Melton LJ Ⅲ,et al.Hip fractures in the elderly:a world-wide projection.Osteoporos Int,1992,2(6):285-9.
[3]Dahlman TC.Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin.Am J Obstet Gynecol,1993,168(4):1265-70.
[4]伍贤平,廖二元,黄干,等.老年妇女不同骨骼部位的骨丢失及其对诊断骨质疏松症的评价.中华老年医学杂志,1999,18(4):217-20.
[5]Halleen JM,Ylipahkala H,Alatalo SL,et al.Serum tartrate-resistant acid phosphatase 5b,but not 5a,correlates with other markers of bone turnover and bone mineral density.Calcif Tissue Int,2002.
[6]Makhluf HA,Mueller SM,Mizuno S,et al.Age-related decline in osteoprotegerin expression by human bone marrow cells cultured in three-dimensional collagen sponges.Biochem Biophys Res Commun,2000,268(3):669"- 72.
[7]Prentice A,Jarjou LM,Stining DM,et al.Biochemical markers of calcium and bone metabolism during 18 months of lactation in Gambian women accustomed to a low calcium intake and in those consuming a calcium supplement.J Clin Endocrinol Metab,1998,83(4):1059-66.
[8]Godfrey K,Walker-Bone K,Robinson S,et al.Neonatal bone mass:influence of parental birthweight,maternal smoking,body composition,and activity during pregnancy.J Bone Mineral Res,2001,16(9):1694-703.
[9]McGuigan FE,Murray L,Gallagher A,et al.Genetic and environmental determinants of peak bone mass in young men and women.J Bone Miner Res,2002,17(7):1273-79.
[10]Heaney RP,Abrams S,Dawson-Hughes B,et al.Peak bone mass.Osteoporos Int,2000,11(12):985-1009.
[11]Takata S,Yasui N.Disuse osteoporosis.J Med Invest,2001,48(3-4):147-56.
[12] Kukla C, Gaebler C, Pichl RW, et al. Predictive geometric factors in a standardized model of femoral neck fracture. Experimental study of cadaveric human femurs. Injury, 2002,33 (5) : 427—33.
[13] Turner CH. Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int, 2002,13 (2) : 97-104.
[14] Felsenberg D, Boonen S. The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. ClinTher,2005;27 (1) :1-11.
[15] Choi K, Goldstein SA. A comparison of the fatigue behavior of human trabecular and cortical bone tissue. J Biomech, 1992,25:1371—81.
[16] WHO (1994) : Assessment of Osteoporotic Fracture Risk and its Role in a Screening for Postmenopausal Osteoporosis. WHO Technical Report Series,Geneva, 1994.
[17] Shifrin LZ, Reis ND, Zinman H, et al. Idiopathic transient osteoporosis of the hip. J Bone and Joint Surg, 1987,69:769-73.
[18] Lasofoxifene: CP 336156, CP-336156. Drugs RD,2005,6 (1) :56-60.
[19] Munoz-Torres M, Alonso G, Raya MP. Calcitonin therapy in osteoporosis. Treat Endocrinol,2004;3 (2) :117-3.
[20] Finkelstein JS, Klibanski A, Schaefer EH, et al. Parathyroid hormone for the prevention of bone loss induced by estrogen deficiency. N Engl J Med, 1994,331:1618-23.
[21] Watson PH, Fraher LJ, Natak, et al. Nuclear localization of the type 1 PTH/PTHrP receptor in rat tissues. J Bone Miner Res, 2000,15: 1033—44.
[22] Hodsman AB, Kisiel M, Adachi JD, et al. Histomorphometric evidence for increased bone turnover in cortical thickness or porosity after 2 years of cyclical hPTH (1-34) therapy in women with severe osteoporosis. Bone, 2000, 27:311-18.
[23] Whitfield JF, Morley P, Willick GE. Parathyroid hormone, its fragments and their analogs for the treatment of osteoporosis. Treat Endocrinol, 2002;1(3) : 175-90.
[24] Lane NE, Sanchez S, Modin GW, et al. Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis results of a randomized controlled clinical trial. J Bone Miner Res, 2000,15:944-51.
[1]Hla MM,Davis JW,Ross PD,et al.A multicenter study of the influence of fat and lean mass on bone mineral content:evidence for differences in their relative influence at major fracture sites.Early Postmenopausal Intervention Cohort(EPIC) Study Group.Am J Clin Nutr,1996,64:354-60.
[2]Lindsay R,Cosman F,Herrington BS,et al.Bone mass and body composition in normal women.J Bone Miner Res,1992,7:55-62.
[3]Tchernof A,Despres JP,Belanger A,et al.Reduced testosterone and adrenal C19 steroid levels in obese men.Metabolism,1995,44:513-9.
[4]Corbould AM,Bawden MJ,Lavranos TC,et al.The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women.Int J Obes Relat Metab Disord,2002,26:165-75.
[5]Schercr PE,Williams S,Fogliano M,et al.A novel serum protein similar to Clq,produced exclusively in adipocytes.J Biol Chem,1995,270:26746-26749.
[6]Maeda K,Okubo K,Shimomura I,et al.cDNA cloning and expression of a novel adipose specific collagen-like factor,apM1(AdiPose Most abundant Gene transcript 1).Biochem Biophys Res Commun,1996,221:286-9.
[7]Arita Y,Kihara S,Ouchi N,et al.Paradoxical decrease of an adipose specific protein,adiponectin,in obesity.Biochem Biophys Res Commun,1999,257:79-83.
[8]Yatagai T,Nagasaka S,Taniguchi A,et al.Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus.Metabolism,2003,52:1274-8.
[9]Kershaw EE,Flier JS.Adipose tissue as an endocrine organ.J Clin Enocrinol Metab,2004,89:2548-56.
[10]Waki H,Yamauchi T,Kamon J,et al.Impaired multimerization of human adiponectinmutants associated with diabetes.Molecular structure and multimer formation of adiponectin.J Biol Chem,2003,278:40352-63.
[11]Vas seur F,Lepretre F,Lacquemant C,et al.The genetics of adiponectin.Curr Diab Rep,2003,3:151-8.
[12]Stumvoll M,Tschritter O,Fritsche A,et al.Association of the T-G polymorphism in adiponectin (exon2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes, 2002,51:37-41.
[13] Pajvani UB, Hankins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thizolidinedione-mediated improvement in insulin sensitivity. J Biol Chem, 2004,279:12152-62.
[14] Pajvani UB , Du X, Combs TP, et al. Structure-function studies of the adiponectin-secreted homone Acrp30/Adiponectin, J Biol Chem 2003, 278:9073-85.
[15] Tsao TS , Murrey HE , Hug C , et al. Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30) . J Biol Chem, 2002,277: 29359-62.
[16] Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature, 2003,423: 762-9.
[17] Wallis GA, Rash B, Sykes B, et al. Mutations within the gene encoding the alpha 1 (X) chain of type X collagen (COL10A1) cause metaphyseal chondrodysplasia type Schmid but not several other forms of metaphyseal chondrodysplasia. J Med Genet, 1996,33:450-7.
[18] Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation, 2000,102:1296-301.
[19] Yokota T, Meka CS, Medina KL, et al. Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins. J Clin Invest, 2002,109:1303-10.
[20] Berner HS, Lyngstadaas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone-forming cells.Bone, 2004, 35: 842-9.
[21] Shinoda Y, Yamaguchi M, Ogata N, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem,2006, 99: 196-208.
[22] Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res, 2005, 309: 99-109.
[23] Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res, 2006,21:1648-56.
[24] Oshima K, Nampei A, Matsuda M, et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun, 2005,331: 520-6.
[25] Kontogianni MD, Dami UG, Routsias JG, et al. Blood leptin and adiponectin as possible mediators of the relation between fat mass and BMD in perimenopausal women. J Bone Miner Res, 2004,19: 546-51.
[26] Huang KC, Cheng WC, Yen RF, et al. Lack of independent relationship between plasma adiponectin, leptin levels and bone density in nondiabetic female adolescents. Clin Endocrinol (Oxf) , 2004; 61:204-8.
[27] Oh KW, Lee WY, Rhee EJ, et al. The relationship between serum resistin,leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men.Clin Endocrinol (Oxf) ,2005,63:131-8.
[28] Lenchik L, Register TC, Hsu FC, et al. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone, 2003,33:646-51.
[29] Jurimae J, Rembel K, Jurimae T, et al. Adiponectin is associated with bone mineral density in perimenopausal women. Horm Metab Res, 2005, 37:297-302.
[30] Jurimae J, Jurimae T. Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral and metabolic variables. Am J Physiol Endocrinol Metab, 2007,293: E42-7.
[31] Misra M, Miller KK, Cord J, et al. Relationships between serum adipokines,insulin levels and bone density in girls with Anorexia Nervosa. J Clin Endocrinol Metab, 2007,92:2046-52.
[32] Richards JB, Valdes AM, et al. Serum Adiponectin and bone mineral density in women. J Clin Endocrinol Metab, 2007,92:1517-23.
[33] Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994,372:425-32.
[34] Wauters M, Considine RV, Van Gaal LF. Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol, 2000,143: 293-311.
[35] Tsiotra PC, Pappa V, Raphis SA, et al. Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: implications for leptin's actions, Metabolism 2000,49: 1537-41.
[36] Trayhurn P, Hoggard N, Mercer JG, et al. Leptin: fundamental aspects. Int J Obes Relat Metab Disord, 1999,23 (Suppl 1) : 22-8.
[37] Reseland JE, Syversen U, Bakke J, et al. Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization.J Bone Miner Res, 2001,16:1426-33.
[38] Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med, 1996, 334:292-5.
[39] Thomas T, Gori F, Khosla S, et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology, 1999,140:1630-8.
[40] Gordeladze JO, Drevon CA, Syversen U, et al. Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization:Impact on differentiation markers, apoptosis, and osteoclastic signaling. J Cell Biochem, 2002, 85: 825-36.
[41] Steppan CM, Crawford DT, Chidsey-Frink KL, et al. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept, 2000,92: 73-8.
[42] Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell, 2000,100:197-207.
[43] Ducy P, Schinke T, Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science, 2000,289:1501-4.
[44] Chanprasertyothin S, Piaseu N, Chailurkit L, et al. Association of circulating leptin with bone mineral density in males and females.J Med Assoc Thai, 2005,88: 655-9.
[45] Sato M, Takeda N, Sarui H, Takami R, et al.Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab, 2001, 86: 5273-6.
[46] Pasco JA, Henry MJ, Kotowicz MA, et al. Serum leptin levels are associated with bone mass in nonobese women.J Clin Endocrinol Metab, 2001, 86:1884-7.
[47] Ruhl CE, Everhart JE. Relationship of serum leptin concentration with bone mineral density in the United States population. J Bone Miner Res, 2002, 17:1896-903.
[48]Wosje KS,Binkley TL,Kalkwarf HJ,et al.Relationships between bone mass and circulating leptin concentrations in Hutterites.Bone,2004,34:1017-22.
[49]Thomas T,Burguera B,Melton LJ 3rd,et al.Role of serum leptin,insulin,and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women.Bone,2001,29:114-20.
[50]Steppan CM,Bailey ST,Bhat S,et al.The hormone resistin links obesity to diabetes.Nature,2001,409:307-12.
[51]Nagaev I,Smith U.Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle.BiochemBiophys Res Commun,2001,285:561-4.
[52]Savage DB,Sewter CP,Klenk ES,et al.Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans.Diabetes,2001,50:2199-202.
[53]Patel L,Buckels AC,Kinghorn IJ,et al.Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators.Biochem Biophys Res Commun,2003,300:472-6.
[54]Schinke T,Haberland M,Jamshidi A,et al.Cloning and functional characterization of resistin-like molecule gamma.Biochem Biophys Res Commun,2004,314:356-62.
[55]Oh KW,Lee WY,Rhee EJ,et al.The relationship between serum resistin,leptin,adiponectin,ghrelin levels and bone mineral density in middle-aged men.Clin Endocrinol(Oxf),2005,63:131-8.
[56]Boucher J,Masri B,Daviaud D,et al.Apelin,a newly identified adipokine up-regulated by insulin and obesity.Endocrinology,2005,146:1764-1771.
[57]O'Dowd BF,Heiber M,Chan A,et al.A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11.Gene,1993,136:355-60.
[58]Tatemoto K,Hosoya M,Habata Y,et al.Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor.Biochem Biophys Res Commun,1998,251:471-6.
[59]Medhurst AD,Jennings CA,Robbins MJ.Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin.J Neurochem,2003,84:1162-72.
[60]Charles CJ.Putative role for apelin in pressure/volume homeostasis and cardiovascular disease.Cardiovasc Hematol Agents Med Chem,2007,5:1-10.
[61]Beltowski J.Apelin and visfatin:unique "beneficial" adipokines upregulated in obesity? Med Sci Monit,2006,12:RA112-9.
[62]Tang SY,Xie H,Yuan LQ,et al.Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways.Peptides,2007,28:708-18.
[63]Xie H,Tang SY,Cui RR,et al.Apelin and its receptor are expressed in human osteoblasts.Regul Pept,2006,134:118-25.
[64]Xie H,Yuan LQ,Luo XH,et al.Apelin suppresses apoptosis of human osteoblasts.Apoptosis,2007,12:247-54.
[65]Fukuhara A,Matsuda M,Nishizawa M,et al.Visfatin:a protein secreted by visceral fat that mimics the effects of insulin.Science,2005,307:426-30.
[66]Berndt J,Kloting N,Kralisch S,et al.Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.Diabetes,2005,54:2911-6.
[67]Chen MP,Chung FM,Chang DM,et al.Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.J Clin Endocrinol Metab,2006,91:295-9.
[68]FukuharaA,MatsudaM,NishizawaM,eta.l Visfatin:a protein secreted by visceral fat thatmimics the effects of insulin.Science,2005,307(5708):426-430.
[69]ChenMP,ChungFM,ChangDM,eta.l Elevated plasma levelofvisfatin/pre-B cell colony-enhancing factor in patientswith type 2 diabetesmellitus.J Clin Endocrino Mletab,2006,91(1):295-99.
[70]Xie H,Tang SY,Luo XH,et al.Insulin-like effects of visfatin on human osteoblasts.Calcif Tissue Int,2007,8:201-10.
[2] Hla MM, Davis JW, Ross PD, et al. A multicenter study of the influence of fat and lean mass on bone mineral content: evidence for differences in their relative influence at major fracture sites. Early Postmenopausal Intervention Cohort (EPIC) Study Group. Am J Clin Nutr, 1996,64:354-60.
[3] Lindsay R, Cosman F, Herrington BS, et al. Bone mass and body composition in normal women. J Bone Miner Res, 1992,7: 55-62.
[4] Tcheraof A, Despres JP, Belanger A, et al. Reduced testosterone and adrenal C19 steroid levels in obese men. Metabolism, 1995,44: 513-9.
[5] Corbould AM, Bawden MJ, Lavranos TC, et al. The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women. Int J Obes Relat Metab Disord, 2002,26:165-75.
[6] Khosla S, Melton LJ 3rd, Atkinson EJ, et al. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women:a key role for bioavailable estrogen. J Clin Endocrinol Metab, 1998, 83:2266-74.
[7] Reid IR, Evans MC, Cooper GJ, et al. Circulating insulin levels are related to bone density in normal postmenopausal women. Am J Physiol, 1993, 265:E655-9.
[8] Barrett-Connor E, Kritz-Silverstein D. Does hyperinsulinemia preserve bone? Diabetes Care, 1996,19:1388-92.
[9] Maeda K, Okubo K, Shimomura I, et al.cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1) . Biochem Biophys Res Commun, 1996,221: 286-9.
[10] Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005, 309: 99-109.
[11] Berner HS, Lyngstadaas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone-forming cells.Bone,2004,35:842-9.
[12]Kershaw EE,Flier JS.Adipose tissue as an endocrine organ.J Clin Enocri Metab,2004,89:2548-56.
[13]Matsubara M,Maruoka S,Katayose S.Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women.Eur J Endocrinol,2002,147:173-80.
[14]Luo XH,Guo L J,Xie H,et al.Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway.J Bone Miner Res,2006,21:1648-56.
[15]Shinoda Y,Yarnaguchi M,Ogata N,et al.Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.J Cell Biochem.2006,99:196-208.
[16]Zhang Y,Proenca R,Maffei M,et al.Positional cloning of the mouse obese gene and its human homologue.Nature,1994,372:425-32.
[17]Thomas T,Burguera B,Melton LJ 3rd,et al.Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women.Metabolism,2000,49:1278-84.
[18]Considine RV,Sinha MK,Heiman ML,et al.Serum immunoreactive-leptin concentrations in normal-weight and obese humans.N Engl J Med,1996,334:292-5.
[19]Wauters M,Considine RV,Van Gaal LF.Human leptin:from an adipocyte hormone to an endocrine mediator.Eur J Endocrinol,2000,143:293-311.
[20]Reseland JE,Syversen U,Bakke I,et al.Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization,J Bone Miner Res.2001,16:1426-33.
[21]Thomas T,Gori F,Khosla S,et al.Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes.Endocrinology,1999,140:1630-8.
[22]Ducy P,Amling M,Takeda S,et al.Leptin inhibits bone formation through a hypothalamic relay:a central control of bone mass.Cell,2000,100:197-207.
[23]Steppan CM,Bailey ST,Bhat S,et al.The hormone resistin links obesity to diabetes.Nature,2001,409:307-12.
[24]Patel L,Buckels AC,Kinghorn IJ,et al.Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators.Biochem Biophys Res Commun, 2003,300:472-6.
[25] Lecka-Czernik B, Moerman EJ, Grant DF, et al. Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology, 2002,143:2376-84.
[26] Oh KW, Lee WY, Rhee EJ, et al.The relationship between serum resistin, leptin,adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clin Endocrinol (Oxf),2005,63:131-8.
[27] Boucher J, Masri B, Daviaud D, et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology, 2005,146:1764-71.
[28] O'Dowd BF, Heiber M, Chan A, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene,1993,136: 355-60.
[29] Tatemoto K, Hosoya M, Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun, 1998,251:471-6.
[30] Medhurst AD, Jennings CA, Robbins MJ. Pharmacological and immunohisto-chemical characterization of the APJ receptor and its endogenous ligand apelin.J Neurochem, 2003,84:1162-1172.
[31] Charles CJ. Putative role for apelin in pressure/volume homeostasis and cardiovascular disease. Cardiovasc Hematol Agents Med Chem, 2007,5:1-10.
[32] Beltowski J. Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? Med Sci Monit, 2006,12: RA112-9.
[33] Lee DK, George SR, O'Dowd BF. Unravelling the roles of the apelin system:prospective therapeutic applications in heart failure and obesity. Trends Pharmacol Sci, 2006,27: 190-4.
[34] Kleinz MJ, Davenport AP. Emerging roles of apelin in biology and medicine.Pharmacol Ther, 2005,107: 198-211.
[35] Wang G, Anini Y, Wei W, et al. Apelin, a new enteric peptide: localization in the gastrointestinal tract, ontogeny, and stimulation of gastric cell proliferation and of cholecystokinin secretion. Endocrinology, 2004,145: 1342-1348.
[36] Tang SY, Xie H, Yuan LQ, et al. Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways. Peptides, 2007, 28: 708-18.
[37]Xie H,Tang SY,Cui RR,et al.Apelin and its receptor are expressed in human osteoblasts.Regul Pept,2006,134:118-25.
[38]Xie H,Yuan LQ,Luo XH,et al.Apelin suppresses apoptosis of human osteoblasts.Apoptosis,2007,12:247-54.
[39]Fukuhara A,Matsuda M,Nishizawa M,et al.Visfatin:a protein secreted by visceral fat that mimics the effects of insulin.Science,2005,307:426-30.
[40]Berndt J,Kloting N,Kralisch S,et al.Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.Diabetes,2005,54:2911-6.
[41]Chen MP,Chung FM,Chang DM,et al.Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.J Clin Endocrinol Metab,2006,91:295-9.
[42]Haider DG,Schindler K,Schaller G,et al.Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding.J Clin Endocrinol Metab,2006,91:1578-81.
[43]Xie H,Tang SY,Luo XH,et al.Insulin-like effects of visfatin on human osteoblasts.Calcif Tissue Int,2007,8:201-10.
[44]李宁华,区品中,朱汉民,等.中国部分地区中老年人群原发性骨质疏松症患病率研究中华骨科杂志,2001,21(5):275-278.
[45]廖二元,伍贤平,邓小戈,等.对中国长沙地区女性骨密度情况的调查.中华内分泌代谢杂志,2000,16:203-207.
[46]孙振球.医学统计学.人民卫生出版社,2002:579.
[47]Wu XP,Liao EY,Zhang H,et al.Establishment of BMD reference plots and determination of peak BMD at multiple skeletal regions in mainland Chinese women and the diagnosis of osteoporosis.Osteoporosis Int,2004,15:71-9.
[48]Liao EY,Wu XP,Deng XG,et al.Aged-related bone mineral density,accumulated bone loss rate and prevalence of osteoporosis at multiple skeletal sites in Chinese women.Osteoporosis Int,2002,13:669-76.
[49]Kanis JA,Melton LJ 3rd,Christiansen C,et al.The diagnosis of osteoporosis.Journal of Bone and Mineral Research,1994,9:1137-41.
[50]王志文,马锦富,杨定悼等.成都地区中老年人群骨密度调查.中国骨质疏松杂志,2000,6(1):40-43. 率的调查.中国骨质疏松杂志,2002,8(4):314-318.
[52]颜晓东,王风,黄忠等.广西南宁地区汉壮族人群骨密度及骨质疏松患病率研究.中国骨质疏松杂志,2003,9(3):268-270.
[53]NIH.Consensus Development panel on osteoporosis.JAMA,2001,85:785-95.
[54]Lau EM,Lee JK,SuriwongpaisalP,et al.T he incidence of hipfracturein four Asianeountries:the Asian Osteoporosis Study(AOS).Osteoporosis Int,2001,12:239-43.
[55]Wasnich RD.Epidemiology of osteoporosis in the United States of America.Osteoporosis Int,1997,7:68-72.
[56]朱国英,王洪复,王莉华,等.绝经后妇女骨质疏松性骨折易发因素的流行病学研究.中国骨质疏松杂志,2004,10(2):172-74.
[57]Zhang m,Shimmura t,Bi lf,et al.Bone mass and lifestyle related factors:a comparative study between Japanese and Inner Mongolian young premenopausal women.Osteoporos Int,2004,15(7):547-51.
[58]Takanobu A,Fumiko M,Toshiko T,et al.Risk of irregular menstrual cycles and low peak bone mass during early a ulthood associated with age at menarche Pediatircs Int,2001,43(5):483-8.
[59]刘继洪,杨延斌,曹海伟,等,成年人骨密度、骨量、体重、年龄、身高、脂肪含量相互关系的研究.实用医学杂志,2002,18(2):146-7.
[60]王莉华,王伟华,王洪复,等.体重和身高对绝经后妇女骨密度值的影响.中华实用医学,2002,4(13):41-3.
[61]Douglas CB,Warren SB,Jane MC,et al.Factors associated with appendicular bone mass in older women.Ann Intent Med,1993,118(9):657-65.
[62]Angela JS.An overview of osteoporosis.Altenr Ther Health Med,2004,10(2):26-34.
[63]Guyen TN,Center JR,Eisman JA.Osteoporosisin elderly men and women:effects of dietary Calcium,physicala etivity,and body mass index.J Bone Miner Res,2000,15(2):322-31.
[64]Susan JW,Hassanail V,Adam BJ,et al.Factors that affect bone mineral accrual in the adolescent growth spurt.J Nutrion,2004,134(3):696-700.
[65]Saija K,Pekka K,Heidi H,et al.Good maintenance of exercise-induced bone Gain with decreased training of female tennis and Squashp layers:prospective 5-year follow-up study of young and old sarters and controls.J Bone Miner Res,2001,16(2):195-201.
[66]朱敏嘉,王风,颜晓东,等.中老年妇女骨质疏松发病危险因素分析.中国老年学杂志,2002,22(4):249-50.
[67]O'Neill TW,Silman AJ,Naves Diaz M.Influence of hormonal and reProductiv factors on the risk of vertebarl defomrity in European woman.European Vertebra of Osteoporosis Study Group.Osteoporosis Int,1997,7(1):72-8.
[68]Cure-Cure C,Cure-Ramirez P,Teran E,et al.Bone-masspeak in multiparity and reduce risk of bone-fractures in menopause.Int J Gynaecol Obstet,2002,76(3):285-91.
[69]李卫敏.骨折、钙和现代饮食.国外医学医学地理分册,2002;23(2).
[70]Hla MM,Davis JW,Ross PD,et al.A multicenter study of the influence of fat and lean mass on bone mineral content:evidence for differences in their relative influence at major fracture sites.Early Postmenopausal Intervention Cohort (EPIC) Study Group.Am J Clin Nutr,1996,64:354-60.
[71]Lindsay R,Cosman F,Herrington BS,et al.Bone mass and body composition in normal women.J Bone Miner Res,1992,7:55-62.
[72]Tchernof A,Despres JP,Belanger A,et al.Reduced testosterone and adrenal C19 steroid levels in obese men.Metabolism,1995,44:513-9.
[73]Corbould AM,Bawden MJ,Lavranos TC,et al.The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women.Int J Obes Relat Metab Disord,2002,26:165-75.
[74]Khosla S,Melton LJ 3rd,Atkinson EJ,et al.Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women:a key role for bioavailable estrogen.J Clin Endocrinol Metab,1998,83:2266-74.
[75]Reid IR,Evans MC,Cooper GJ,et al.Circulating insulin levels are related to bone density in normal postmenopausal women.Am J Physiol,1993,265:E655-9.
[76]Barrett-Connor E,Kritz-Silverstein D.Does hyperinsulinemia preserve bone?Diabetes Care,1996,19:1388-92.
[77]Maeda K,Okubo K,Shimomura I,et al.cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1) . Biochem Biophys Res Commun, 1996,221: 286-9.
[78] Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Enocri Metab, 2004, 89:2548-56.
[79] Matsubara M, Maruoka S, Katayose S. Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol, 2002,147:173-80.
[80] Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005,309: 99-109.
[81] Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res, 2006,21:1648-56.
[82] Shinoda Y, Yamaguchi M, Ogata N, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem, 2006,99:196-208.
[83] Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994,372:425-32.
[84] Thomas T, Burguera B, Melton LJ 3rd, et al. Relationship of serum leptin levels with body composition and sex steroid and insulin levels in men and women.Metabolism, 2000,49:1278-84.
[85] Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med, 1996, 334:292-5.
[86] Wauters M, Considine RV, Van Gaal LF. Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol, 2000,143: 293-311.
[87] Reseland JE, Syversen U, Bakke I, et al. Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization.J Bone Miner Res, 2001,16: 1426-33.
[88] Thomas T, Gori F, Khosla S, et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology, 1999,140: 1630-8.
[89] Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell, 2000,100:197-207.
[90] Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature, 2001,409: 307-12.
[91] Patel L, Buckels AC, Kinghorn IJ, et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun, 2003,300:472-6.
[92] Lecka-Czernik B, Moerman EJ, Grant DF, et al. Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology, 2002,143:2376-84.
[93] Oh KW, Lee WY, Rhee EJ, et al. The relationship between serum resistin,leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men.Clin Endocrinol (Oxf) , 2005, 63:131-8.
[94] Boucher J, Masri B, Daviaud D, et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology, 2005,146:1764-71.
[95] O'Dowd BF, Heiber M, Chan A, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene,1993,136: 355-60.
[96] Tatemoto K, Hosoya M, Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun, 1998,251:471-6.
[97] Medhurst AD, Jennings CA, Robbins MJ. Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin. J Neurochem, 2003, 84:1162-1172.
[98] Charles CJ. Putative role for apelin in pressure/volume homeostasis and cardiovascular disease. Cardiovasc Hematol Agents Med Chem, 2007,5:1-10.
[99] Beltowski J. Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? Med Sci Monit, 2006,12: RA112-9.
[100] Tang SY, Xie H, Yuan LQ, et al. Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways. Peptides, 2007,28: 708-18.
[101] Xie H, Tang SY, Cui RR, et al. Apelin and its receptor are expressed in human osteoblasts. Regul Pept, 2006,134 (2-3) :118-25.
[102] Xie H, Yuan LQ, Luo XH, et al. Apelin suppresses apoptosis of human osteoblasts.Apoptosis,2007,12:247-54.
[103]Fukuhara A,Matsuda M,Nishizawa M,et al.Visfatin:a protein secreted by visceral fat that mimics the effects of insulin.Science,2005,307:426-30.
[104]Berndt J,Kloting N,Kralisch S,et al.Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.Diabetes,2005,54:2911-6.
[105]Chen MP,Chung FM,Chang DM,et al.Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.J Clin Endocrinol Metab,2006,91:295-9.
[106]Xie H,Tang SY,Luo XH,et al.Insulin-like effects of visfatin on human osteoblasts.Calcif Tissue Int,2007,8:201-10.
[107]Lim S,Joung H,Shin CS,et al.Body composition changes with age have gender-specific impacts on bone mineral density.Bone,2004,35:792-8.
[108]Pongchaiyakul C,Nguyen TV,Kosulwat V,et al.Contribution of lean tissue mass to the urban-rural difference in bone mineral density.Osteoporos Int,2005,16:1761-8.
[109]Wang MC,Bachrach LK,Van Loan M,et al.The relative contributions of lean tissue mass and fat mass to bone density in young women.Bone,2005,37:474-81.
[110]Li S,Wagner R,Holm K,et al.Relationship between soft tissue body composition and bone mass in perimenopausal women.Maturitas,2004,47:99-105.
[111]Van Langendonck L,Claessens AL,Lefewe J,et al.Association between bone mineral density(DXA),body structure,and body composition in middle-aged men.Am J Hum Biol,2002,14:735-42.
[112]Capozza RF,Cointry GR,Cure-Ramirez P,et al.A DXA study of muscle-bone relationships in the whole body and limbs of 2512 normal men and pre- and post-menopausal women.Bone,2004,35:283-95.
[113]Kontogianni MD,Dafni UG,Routsias JG,et al.Blood leptin and adiponectin as possible mediators of the relation between fat mass and BMD in perimenopausal women.J Bone Miner Res,2004,19:546-51.
[114]Huang KC,Cheng WC,Yen RF,et al.Lack of independent relationship between plasma adiponectin,leptin levels and bone density in nondiabetic female adolescents.Clin Endocrinol(Oxf),2004,61:204-8.
[115] Zhao LJ, Liu YJ, Liu PY, et al. Relationship of obesity with osteoporosis. J Clin Endocrinol Metab, 2007,92:1640-6.
[116] Ijuin M, Douchi T, Matsuo T, et al. Difference in the effects of body composition on bone mineral density between pre- and postmenopausal women.Maturitas, 2002,43 (4) :239-44.
[117] Douchi T, Kuwahata R, Matsuo T, et al. Relative contribution of lean and fat mass component to bone mineral density in males. J Bone Miner Metab, 2003,21:17-21.
[118] Blain H, Carriere I, Favier F, Jeandel C, Papoz L; EPIDOS Study Group. Body weight change since menopause and percentage body fat mass are predictors of subsequent bone mineral density change of the proximal femur in women aged 75 years and older: results of a 5 year prospective study. Calcif Tissue Int, 2004,75:32-9.
[119] Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature, 2003,423: 762-9.
[120] Wallis GA, Rash B, Sykes B,et al. Mutations within the gene encoding the alpha 1 (X) chain of type X collagen (COL10A1) cause metaphyseal chondrodysplasia type Schmid but not several other forms of metaphyseal chondrodysplasia. J Med Genet, 1996,33:450-7.
[121] Ouchi N, Kihara S, Arita Y, et al.Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation, 2000,102:1296-301.
[122] Yokota T, Meka CS, Medina KL, et al. Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins. J Clin Invest, 2002,109:1303-10.
[123] Bemer HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA,Syversen U, Reseland JE. Adiponectin and its receptors are expressed in bone-forming cells.Bone, 2004,35: 842-9.
[124] Oshima K, Nampei A, Matsuda M,et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun, 2005, 331: 520-6.
[125] Lenchik L, Register TC, Hsu FC, et al. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone, 2003, 33: 646-51.
[126]J(u|¨)rim(a|¨)e J,Rembel K,J(u|¨)rim(a|¨)e T,et al.Adiponectin is associated with bone mineral density in perimenopausal women.Horm Metab Res,2005,37:297-302.
[127]J(u|¨)rim(a|¨)e J,J(u|¨)rim(a|¨)e T.Plasma adiponectin concentration in healthy pre- and postmenopausal women:relationship with body composition,bone mineral and metabolic variables.Am J Physiol Endocrinol Metab,2007,293:E42-7.
[128]Misra M,Miller KK,Cord J,wt al.Relationships between Serum Adipokines,Insulin Levels and Bone Density in Girls with Anorexia Nervosa.J Clin Endocrin Metab,2007,92:2046-52.
[129]Richards JB,Valdes AM,et al.Serum Adiponectin and Bone Mineral Density in Women.J Clin Endocrin Metab,2007,92:1517-23.
[130]Aubin JE,Bonnelye E.Osteoprotegerin and its ligand:a new paradigm for regulation of osteoclastogenesis and bone resorption.Osteoporos Int,2000,11:905-13.
[131]Suda T,Takahashi N,Udagawa N,et al.Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families.Endocr Rev,1999,20:345-57.
[132]Takahashi N,Udagawa N,Suda T.A new member of tumor necrosis factor ligand family,ODF/OPGL/TRANCE/RANKL,regulate sosteoclast differentiation and function.Biochem Biophys Res Commun,1999,256:449-55.
[133]Gordeladze JO,Drevon CA,Syversen U,et al.Leptin stimulates human osteoblastic cell proliferation,de novo collagen synthesis,and mineralization:Impact on differentiation markers,apoptosis,and osteoclastic signaling.J Cell Biochem,2002,85:825-36.
[134]Steppan CM,Crawford DT,Chidsey-Frink KL,et al.Leptin is a potent stimulator of bone growth in ob/ob mice.Regul Pept,2000,92:73-8.
[135]Duty P,Schinke T,Karsenty G.The osteoblast:a sophisticated fibroblast under central surveillance.Science,2000,289:1501-4.
[136]Chanprasertyothin S,Piaseu N,Chailurkit L,et al.Association of circulating leptin with bone mineral density in males and females.J Med Assoc Thai,2005,88:655-9.
[137]Sato M,Takeda N,Sarui H,Takami R,et al.Association between serum leptin concentrations and bone mineral density,and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab, 2001, 86: 5273-6.
[138] Pasco JA, Henry MJ, Kotowicz MA, et al. Serum leptin levels are associated with bone mass in nonobese women.J Clin Endocrinol Metab, 2001, 86:1884-7.
[139] Ruhl CE, Everhart JE. Relationship of serum leptin concentration with bone mineral density in the United States population. J Bone Miner Res, 2002, 17:1896-903.
[140] Wosje KS, Binkley TL, Kalkwarf HJ, et al. Relationships between bone mass and circulating leptin concentrations in Hutterites. Bone, 2004,34: 1017-22.
[141] Thomas T, Burguera B, Melton LJ 3rd, et al. Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone, 2001,29: 114-20.
[142] Zhong N, Wu XP, Xu ZR, et al. Relationship of serum leptin with age, body weight, body mass index, and bone mineral density in healthy mainland Chinese women.Clin Chim Acta, 2005, 351: 161-8.
[143] Sinha MK, Ohannesian JP, Heiman ML, et al. Nocturnal rise of leptin in lean,obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest, 1996,97:1344-7.
[144] Nagaev I , Smith U. Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. BiochemBiophys Res Commun,2001,285: 561-4.
[145] Savage DB, Sewter CP, Klenk ES, et al. Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes, 2001, 50:2199-202.
[146] Schinke T, Haberland M, Jamshidi A, et al. Cloning and functional characterization of resistin-like molecule gamma. Biochem Biophys Res Commun, 2004,314: 356-62.
[147] Gonnelli S, Cepollaro C, Gennari L, Montagnani A, et al. Quantitative ultrasound and dual-energy X-ray absorptiometry in the prediction of fragility fracture in men. Osteoporos Int, 2005,16: 963-8.
[148] Broe KE, Hannan MT, Kiely DK, et al. Predicting fractures using bone mineral density: a prospective study of long-term care residents. Osteoporos Int, 2000,11:765-71.
[149]单鹏飞,伍贤平,廖二元等.女性骨代谢转换生化标物各骨密度随年龄变化及其相互关系.中华老年医学杂志,2005,24:431-4.
[150]Iki M,Akiba T,Matsumoto T,Nishino H,Kagamimori S,Kagawa Y,Yoneshima H;JPOS Study Group.Reference database of biochemical markers of bone turnover for the Japanese female population.Japanese Population-based Osteoporosis(JPOS) Study.Osteoporos Int,2004,15:981-91.
[151]Gomes B Jr,Ardakani S,Ju J,et al.Monoclonal antibody assay for measuring bone alkaline phosphatase activity in serum.Clin Chem,1995,41:1560-66.
[152]Hanson DA,Weis MA,Bollen AM,et al.A specific immunoassay for monitoring human bone resorption:quantitation of type Ⅰ collagen croo-linked N-telopeptides in urine.J Bone Miner Res,1992,7:1251-8.
[153]Clemens JD,Herrick MV,Singer FR,et al.Evidence that serum NTx (collagen-type I N-telopeptides) can act as an immunochemical marker of bone resorption.Clin Chem,1997,43:2058-63.
[154]杨伟民.骨代谢生化指标与骨质疏松症.中国骨质疏松杂志,2004,10:118-9.
[155]Blain H,Vuillemin A,Guillemin F,et al.Serum leptin level is a predictor of bone mineral density in postmenopausal women.J Clin Endocrinol Metab,2002,87:1030-5.
[156]Sato M,Takeda N,Sarui H,et al.Association between serum leptin concentrations and bone mineral density,and biochemical markers of bone turnover in adult men.J Clin Endocrinol Metab,2001,86:5273-6.
[157]Scariano JK,Garry PJ,Montoya GD,et al.Serum leptin levels,bone mineral density and osteoblast alkaline phosphatase activity in elderly men and women.Mech Ageing Dev,2003,124:281-6.
[158]Tamura T,Yoneda M,Yamane K,et al.Serum leptin and adiponectin are positively associated with bone mineral density at the distal radius in patients with type 2 diabetes mellitus.Metabolism,2007,56:623-8.
[159]Luo XH,Guo LJ,Shan PF,et al.Relationship of circulating MMP-2,MMP-1,and TIMP-1 levels with bone biochemical markers and bone mineral density in postmenopausal Chinese women.Osteoporos Int,2006,17:521-6.
[160]Richards JB,Valdes AM,et al.Serum Adiponectin and Bone Mineral Density in Women.J Clin Endocrin Metab,2007,92:1517-23.
[161] J(?)rim(?)e J, Rembel K, J(?)rim(?)e T, et al. Adiponectin is associated with bone mineral density in perimenopausal women. Horm Metab Res, 2005, 37:297-302.
[162] Misra M, Miller KK, Cord J, wt al. Relationships between Serum Adipokines,Insulin Levels and Bone Density in Girls with Anorexia Nervosa. J Clin Endocrin Metab, 2007,92:2046-52.
[163] Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res, 2006,21:1648-56.
[164] Aubin JE, Bonnelye E. Osteoprotegerin and its ligand: a new paradigm for regulation of osteoclastogenesis and bone resorption. Osteoporos Int, 2000, 11:905-13.
[165] Suda T, Takahashi N, Udagawa N, et al. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev, 1999,20: 345-57.
[166] Takahashi N, Udagawa N, Suda T. A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function. Biochem Biophys Res Commun, 1999, 256:449-55.
[167] Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005,309: 99-109.
[168] Minisola S, Pacitti MT, Ombricolo E, et al. Bone turnover and its relationship with bone mineral density in pre- and postmenopausal women with or without fractures. Maturitas, 1998,29:265-70.
[169] Khosla S, Melton LJ 3rd, Atkinson EJ, et al. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women:a key role for bioavailable estrogen. J Clin Endocrinol Metab, 1998, 83:2266-74.
[170] Szulc P, Garnero P, Munoz F, et al. Cross-sectional evaluation of bone metabolism in men. J Bone Miner Res, 2001,16: 1642-50.
[171] Khosla S, Melton LJ III, Atkinson EJ, et al. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women:a key role for bioavailable estrogen. J Clin Endocrinol Metab, 1998, 83: 2266-74.
[172] Goemaere S, Van Pottelbergh I, Zmierczak H, et al. Inverse association between bone turnover rate and bone mineral density in community-dwelling men ＞70 years of age: no major role of sex steroid status. Bone, 2001,29:286-91.
[173] Tsai KS, Pan WH, Hsu SHJ, et al. Sexual differences in bone markers and bone mineral density of normal Chinese. Calcif Tissue Int, 1996,59:454-60.
[174] Scopacasa F, Wishart JM, Need AG, et al. Bone Density and Bone-Related Biochemical Variables in Normal Men A Longitudinal Study. Gerontol A Biol Sci Med Sci, 2002,57: M385-91.
[1]廖二元,伍贤平,邓小戈,等.对中国长沙地区女性骨密度情况的调查.中华内分泌代谢杂志,2000,16:203-7.
[2]Cooper C,Campion G,Melton LJ Ⅲ,et al.Hip fractures in the elderly:a world-wide projection.Osteoporos Int,1992,2(6):285-9.
[3]Dahlman TC.Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin.Am J Obstet Gynecol,1993,168(4):1265-70.
[4]伍贤平,廖二元,黄干,等.老年妇女不同骨骼部位的骨丢失及其对诊断骨质疏松症的评价.中华老年医学杂志,1999,18(4):217-20.
[5]Halleen JM,Ylipahkala H,Alatalo SL,et al.Serum tartrate-resistant acid phosphatase 5b,but not 5a,correlates with other markers of bone turnover and bone mineral density.Calcif Tissue Int,2002.
[6]Makhluf HA,Mueller SM,Mizuno S,et al.Age-related decline in osteoprotegerin expression by human bone marrow cells cultured in three-dimensional collagen sponges.Biochem Biophys Res Commun,2000,268(3):669"- 72.
[7]Prentice A,Jarjou LM,Stining DM,et al.Biochemical markers of calcium and bone metabolism during 18 months of lactation in Gambian women accustomed to a low calcium intake and in those consuming a calcium supplement.J Clin Endocrinol Metab,1998,83(4):1059-66.
[8]Godfrey K,Walker-Bone K,Robinson S,et al.Neonatal bone mass:influence of parental birthweight,maternal smoking,body composition,and activity during pregnancy.J Bone Mineral Res,2001,16(9):1694-703.
[9]McGuigan FE,Murray L,Gallagher A,et al.Genetic and environmental determinants of peak bone mass in young men and women.J Bone Miner Res,2002,17(7):1273-79.
[10]Heaney RP,Abrams S,Dawson-Hughes B,et al.Peak bone mass.Osteoporos Int,2000,11(12):985-1009.
[11]Takata S,Yasui N.Disuse osteoporosis.J Med Invest,2001,48(3-4):147-56.
[12] Kukla C, Gaebler C, Pichl RW, et al. Predictive geometric factors in a standardized model of femoral neck fracture. Experimental study of cadaveric human femurs. Injury, 2002,33 (5) : 427—33.
[13] Turner CH. Biomechanics of bone: determinants of skeletal fragility and bone quality. Osteoporos Int, 2002,13 (2) : 97-104.
[14] Felsenberg D, Boonen S. The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. ClinTher,2005;27 (1) :1-11.
[15] Choi K, Goldstein SA. A comparison of the fatigue behavior of human trabecular and cortical bone tissue. J Biomech, 1992,25:1371—81.
[16] WHO (1994) : Assessment of Osteoporotic Fracture Risk and its Role in a Screening for Postmenopausal Osteoporosis. WHO Technical Report Series,Geneva, 1994.
[17] Shifrin LZ, Reis ND, Zinman H, et al. Idiopathic transient osteoporosis of the hip. J Bone and Joint Surg, 1987,69:769-73.
[18] Lasofoxifene: CP 336156, CP-336156. Drugs RD,2005,6 (1) :56-60.
[19] Munoz-Torres M, Alonso G, Raya MP. Calcitonin therapy in osteoporosis. Treat Endocrinol,2004;3 (2) :117-3.
[20] Finkelstein JS, Klibanski A, Schaefer EH, et al. Parathyroid hormone for the prevention of bone loss induced by estrogen deficiency. N Engl J Med, 1994,331:1618-23.
[21] Watson PH, Fraher LJ, Natak, et al. Nuclear localization of the type 1 PTH/PTHrP receptor in rat tissues. J Bone Miner Res, 2000,15: 1033—44.
[22] Hodsman AB, Kisiel M, Adachi JD, et al. Histomorphometric evidence for increased bone turnover in cortical thickness or porosity after 2 years of cyclical hPTH (1-34) therapy in women with severe osteoporosis. Bone, 2000, 27:311-18.
[23] Whitfield JF, Morley P, Willick GE. Parathyroid hormone, its fragments and their analogs for the treatment of osteoporosis. Treat Endocrinol, 2002;1(3) : 175-90.
[24] Lane NE, Sanchez S, Modin GW, et al. Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis results of a randomized controlled clinical trial. J Bone Miner Res, 2000,15:944-51.
[1]Hla MM,Davis JW,Ross PD,et al.A multicenter study of the influence of fat and lean mass on bone mineral content:evidence for differences in their relative influence at major fracture sites.Early Postmenopausal Intervention Cohort(EPIC) Study Group.Am J Clin Nutr,1996,64:354-60.
[2]Lindsay R,Cosman F,Herrington BS,et al.Bone mass and body composition in normal women.J Bone Miner Res,1992,7:55-62.
[3]Tchernof A,Despres JP,Belanger A,et al.Reduced testosterone and adrenal C19 steroid levels in obese men.Metabolism,1995,44:513-9.
[4]Corbould AM,Bawden MJ,Lavranos TC,et al.The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women.Int J Obes Relat Metab Disord,2002,26:165-75.
[5]Schercr PE,Williams S,Fogliano M,et al.A novel serum protein similar to Clq,produced exclusively in adipocytes.J Biol Chem,1995,270:26746-26749.
[6]Maeda K,Okubo K,Shimomura I,et al.cDNA cloning and expression of a novel adipose specific collagen-like factor,apM1(AdiPose Most abundant Gene transcript 1).Biochem Biophys Res Commun,1996,221:286-9.
[7]Arita Y,Kihara S,Ouchi N,et al.Paradoxical decrease of an adipose specific protein,adiponectin,in obesity.Biochem Biophys Res Commun,1999,257:79-83.
[8]Yatagai T,Nagasaka S,Taniguchi A,et al.Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus.Metabolism,2003,52:1274-8.
[9]Kershaw EE,Flier JS.Adipose tissue as an endocrine organ.J Clin Enocrinol Metab,2004,89:2548-56.
[10]Waki H,Yamauchi T,Kamon J,et al.Impaired multimerization of human adiponectinmutants associated with diabetes.Molecular structure and multimer formation of adiponectin.J Biol Chem,2003,278:40352-63.
[11]Vas seur F,Lepretre F,Lacquemant C,et al.The genetics of adiponectin.Curr Diab Rep,2003,3:151-8.
[12]Stumvoll M,Tschritter O,Fritsche A,et al.Association of the T-G polymorphism in adiponectin (exon2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes, 2002,51:37-41.
[13] Pajvani UB, Hankins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thizolidinedione-mediated improvement in insulin sensitivity. J Biol Chem, 2004,279:12152-62.
[14] Pajvani UB , Du X, Combs TP, et al. Structure-function studies of the adiponectin-secreted homone Acrp30/Adiponectin, J Biol Chem 2003, 278:9073-85.
[15] Tsao TS , Murrey HE , Hug C , et al. Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30) . J Biol Chem, 2002,277: 29359-62.
[16] Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature, 2003,423: 762-9.
[17] Wallis GA, Rash B, Sykes B, et al. Mutations within the gene encoding the alpha 1 (X) chain of type X collagen (COL10A1) cause metaphyseal chondrodysplasia type Schmid but not several other forms of metaphyseal chondrodysplasia. J Med Genet, 1996,33:450-7.
[18] Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation, 2000,102:1296-301.
[19] Yokota T, Meka CS, Medina KL, et al. Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins. J Clin Invest, 2002,109:1303-10.
[20] Berner HS, Lyngstadaas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone-forming cells.Bone, 2004, 35: 842-9.
[21] Shinoda Y, Yamaguchi M, Ogata N, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem,2006, 99: 196-208.
[22] Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res, 2005, 309: 99-109.
[23] Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res, 2006,21:1648-56.
[24] Oshima K, Nampei A, Matsuda M, et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun, 2005,331: 520-6.
[25] Kontogianni MD, Dami UG, Routsias JG, et al. Blood leptin and adiponectin as possible mediators of the relation between fat mass and BMD in perimenopausal women. J Bone Miner Res, 2004,19: 546-51.
[26] Huang KC, Cheng WC, Yen RF, et al. Lack of independent relationship between plasma adiponectin, leptin levels and bone density in nondiabetic female adolescents. Clin Endocrinol (Oxf) , 2004; 61:204-8.
[27] Oh KW, Lee WY, Rhee EJ, et al. The relationship between serum resistin,leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men.Clin Endocrinol (Oxf) ,2005,63:131-8.
[28] Lenchik L, Register TC, Hsu FC, et al. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone, 2003,33:646-51.
[29] Jurimae J, Rembel K, Jurimae T, et al. Adiponectin is associated with bone mineral density in perimenopausal women. Horm Metab Res, 2005, 37:297-302.
[30] Jurimae J, Jurimae T. Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral and metabolic variables. Am J Physiol Endocrinol Metab, 2007,293: E42-7.
[31] Misra M, Miller KK, Cord J, et al. Relationships between serum adipokines,insulin levels and bone density in girls with Anorexia Nervosa. J Clin Endocrinol Metab, 2007,92:2046-52.
[32] Richards JB, Valdes AM, et al. Serum Adiponectin and bone mineral density in women. J Clin Endocrinol Metab, 2007,92:1517-23.
[33] Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994,372:425-32.
[34] Wauters M, Considine RV, Van Gaal LF. Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol, 2000,143: 293-311.
[35] Tsiotra PC, Pappa V, Raphis SA, et al. Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: implications for leptin's actions, Metabolism 2000,49: 1537-41.
[36] Trayhurn P, Hoggard N, Mercer JG, et al. Leptin: fundamental aspects. Int J Obes Relat Metab Disord, 1999,23 (Suppl 1) : 22-8.
[37] Reseland JE, Syversen U, Bakke J, et al. Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization.J Bone Miner Res, 2001,16:1426-33.
[38] Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med, 1996, 334:292-5.
[39] Thomas T, Gori F, Khosla S, et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology, 1999,140:1630-8.
[40] Gordeladze JO, Drevon CA, Syversen U, et al. Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization:Impact on differentiation markers, apoptosis, and osteoclastic signaling. J Cell Biochem, 2002, 85: 825-36.
[41] Steppan CM, Crawford DT, Chidsey-Frink KL, et al. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept, 2000,92: 73-8.
[42] Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell, 2000,100:197-207.
[43] Ducy P, Schinke T, Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science, 2000,289:1501-4.
[44] Chanprasertyothin S, Piaseu N, Chailurkit L, et al. Association of circulating leptin with bone mineral density in males and females.J Med Assoc Thai, 2005,88: 655-9.
[45] Sato M, Takeda N, Sarui H, Takami R, et al.Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab, 2001, 86: 5273-6.
[46] Pasco JA, Henry MJ, Kotowicz MA, et al. Serum leptin levels are associated with bone mass in nonobese women.J Clin Endocrinol Metab, 2001, 86:1884-7.
[47] Ruhl CE, Everhart JE. Relationship of serum leptin concentration with bone mineral density in the United States population. J Bone Miner Res, 2002, 17:1896-903.
[48]Wosje KS,Binkley TL,Kalkwarf HJ,et al.Relationships between bone mass and circulating leptin concentrations in Hutterites.Bone,2004,34:1017-22.
[49]Thomas T,Burguera B,Melton LJ 3rd,et al.Role of serum leptin,insulin,and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women.Bone,2001,29:114-20.
[50]Steppan CM,Bailey ST,Bhat S,et al.The hormone resistin links obesity to diabetes.Nature,2001,409:307-12.
[51]Nagaev I,Smith U.Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle.BiochemBiophys Res Commun,2001,285:561-4.
[52]Savage DB,Sewter CP,Klenk ES,et al.Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans.Diabetes,2001,50:2199-202.
[53]Patel L,Buckels AC,Kinghorn IJ,et al.Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators.Biochem Biophys Res Commun,2003,300:472-6.
[54]Schinke T,Haberland M,Jamshidi A,et al.Cloning and functional characterization of resistin-like molecule gamma.Biochem Biophys Res Commun,2004,314:356-62.
[55]Oh KW,Lee WY,Rhee EJ,et al.The relationship between serum resistin,leptin,adiponectin,ghrelin levels and bone mineral density in middle-aged men.Clin Endocrinol(Oxf),2005,63:131-8.
[56]Boucher J,Masri B,Daviaud D,et al.Apelin,a newly identified adipokine up-regulated by insulin and obesity.Endocrinology,2005,146:1764-1771.
[57]O'Dowd BF,Heiber M,Chan A,et al.A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11.Gene,1993,136:355-60.
[58]Tatemoto K,Hosoya M,Habata Y,et al.Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor.Biochem Biophys Res Commun,1998,251:471-6.
[59]Medhurst AD,Jennings CA,Robbins MJ.Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin.J Neurochem,2003,84:1162-72.
[60]Charles CJ.Putative role for apelin in pressure/volume homeostasis and cardiovascular disease.Cardiovasc Hematol Agents Med Chem,2007,5:1-10.
[61]Beltowski J.Apelin and visfatin:unique "beneficial" adipokines upregulated in obesity? Med Sci Monit,2006,12:RA112-9.
[62]Tang SY,Xie H,Yuan LQ,et al.Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways.Peptides,2007,28:708-18.
[63]Xie H,Tang SY,Cui RR,et al.Apelin and its receptor are expressed in human osteoblasts.Regul Pept,2006,134:118-25.
[64]Xie H,Yuan LQ,Luo XH,et al.Apelin suppresses apoptosis of human osteoblasts.Apoptosis,2007,12:247-54.
[65]Fukuhara A,Matsuda M,Nishizawa M,et al.Visfatin:a protein secreted by visceral fat that mimics the effects of insulin.Science,2005,307:426-30.
[66]Berndt J,Kloting N,Kralisch S,et al.Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.Diabetes,2005,54:2911-6.
[67]Chen MP,Chung FM,Chang DM,et al.Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.J Clin Endocrinol Metab,2006,91:295-9.
[68]FukuharaA,MatsudaM,NishizawaM,eta.l Visfatin:a protein secreted by visceral fat thatmimics the effects of insulin.Science,2005,307(5708):426-430.
[69]ChenMP,ChungFM,ChangDM,eta.l Elevated plasma levelofvisfatin/pre-B cell colony-enhancing factor in patientswith type 2 diabetesmellitus.J Clin Endocrino Mletab,2006,91(1):295-99.
[70]Xie H,Tang SY,Luo XH,et al.Insulin-like effects of visfatin on human osteoblasts.Calcif Tissue Int,2007,8:201-10.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |