补肾健脾活血法对绝经后骨质疏松症患者骨转化的影响
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摘要
背景
骨质疏松症(osteoporosis, OP)是一种以低骨量和骨组织微结构破坏为特征,导致骨骼脆性增加和易发生骨折的全身性疾病,其发生机制包括衰老因素、激素调控、遗传因素、细胞因子、营养因素、物理因素、生活习惯等,骨质疏松症的筛查诊断指标有多种,由于低骨量是骨质疏松公认的最可靠的高危因素,骨质疏松症属代谢性骨病之一。骨代谢异常是由破骨细胞骨吸收活性与成骨细胞骨形成活性所构成的骨重建机制失去平衡所致,在骨重建过程中骨量过多流失,并损害骨结构,依据骨重建异常的病理可分为高转换型骨质疏松症和低转换型骨质疏松症。既往研究表明绝经后骨质疏松症属于高转换型,骨转换生化指标的变化与骨丢失的发生、程度及转归相一致,而且早于骨密度,骨转换生化指标反映的是整体的骨细胞活性,因此在预测及评估妇女绝经后的骨量变化及骨质疏松筛查方面有一定的实用价值,而且治疗绝经后骨质疏松症并非每一种药对每个患者都有效,而骨转换指标较骨密度能更早地反映出骨代谢对治疗的反应,能更早地预测患者的治疗效果,骨形成标记物常用血清骨特异性碱性磷酸酶(B-ALP)、骨钙素(BGP)指标,骨吸收标记物常用抗酒石酸酸性磷酸酶(TRACP)、尿脱氧吡啶啉(DPD)排泄率。根据所述及的临床症状及发病机理,骨质疏松症与“骨痹”“骨痿”等颇为相似。导师庄洪教授分析认为其中医发病机制为肾气肾精亏虚、脾胃功能失调、血瘀阻滞经脉,并以补肾健脾活血为法则,同所在研究单位研发骨康方,该复方的组成正是从改善脏腑整体功能着手,以补脾益肾、改善微循环为手段,用来预防和治疗绝经后骨质疏松症,其作用机制可能是该方组成中含有类性激素样物质,维护体内激素代谢,对下丘脑-垂体-性腺轴的各个层次均有改善作用,进而通过抑制破骨细胞的骨吸收并促进成骨细胞的骨形成,从而恢复骨吸收与骨形成的偶联机制来实现的,经临床观察和动物实验证实其具有抑制骨吸收和促进骨形成的双重作用,是防治绝经后骨质疏松症的理想药物。
目的
探讨补肾健脾活血法(骨康方)对绝经后骨质疏松患者骨转化的影响,临床观察骨康方以及钙剂能否有效抑制骨的高转化率,以及对骨形成和骨吸收指标的影响；临床观察骨康方以及钙剂能否预防和治疗绝经后骨质疏松,并且比较两者之间的疗效。对骨质疏松症的发生机理以及中医药的应用机理进行分析探讨,填补骨康方对骨吸收以及骨形成指标的临床数据,为进一步表明骨康方的临床有效性以及优越性。
方法
选择经骨密度测定及临床检查确诊为绝经后骨质疏松症患者且自愿加入临床实验研究,共58例,根据骨密度检查时的编号随机分为二组,即骨康组,对照组,两组均给予宣传教育,对照组给予口服钙尔奇D片,每日1次,1片／次。骨康组给予骨康(1剂／日)+钙尔奇D(每日1次,1片／次),给药方法采用循环间歇性给药,即连续服用3周,休息1周。4周为一疗程,连续6个疗程。采用双能X线骨密度仪测定患者治疗前后骨密度,采用酶联免疫法测定患者治疗前后血清骨碱性磷酸酶、骨钙素、抗酒石酸酸性磷酸酶、尿脱氧吡啶啉、尿肌酐,组间与各组治疗前后资料比较用t检验,取双侧α<0.05作为统计显著差异的标准。
结果
根据统计结果提示：骨康组与对照组年龄、体重、身高、体重指数、绝经年限之间比较,P>0.05,无统计学意义,骨康组与对照组治疗前骨密度、B-ALP、BGP、TRACP、DPD排泄率比较,P>0.05,无统计学意义,说明根据入选病例时骨密度的顺序号随机分组合理,两组之间具有可比性。骨康组与对照组治疗后骨密度、B-ALP比较,P>0.05无统计学意义,治疗后BGP、TRACP、DPD排泄率比较P<0.01具有显著性差异。骨康组治疗前后骨密度无统计学意义,治疗前后B-ALP、BGP、TRACP、DPD排泄率具有显著性差异。对照组治疗前后骨密度、TRACP、DPD排泄率比较,P>0.05,无统计学意义,治疗前后B-ALP浓度比较,P<0.05,具有统计学意义,治疗前后BGPP<0.01具有显著性差异。
结论
1.骨康方以及钙剂组在对患者的骨密度影响方面均无明显差异,但从骨密度的绝对值以及趋势来看,无论骨康方以及钙剂均能提高患者的骨密度,且骨康方组较钙剂组更为明显；
2.钙剂以及中药骨康均能调节血清BGP和B-ALP浓度,对成骨细胞的活性有一定的影响,骨康方配合钙剂较单纯钙剂组效果更为明显,能有效抑制血清ALP、BGP水平的快速升高,以保持适度的骨转换,趋于正常和平衡的骨代谢。中药骨康方可能是通过调节全身激素及骨髓中细胞因子,抑制代偿性增强的成骨细胞活性,使成骨细胞和破骨细胞活性趋于平衡；
3.单纯服钙剂不足以抑制骨吸收,降低骨转换,骨康方能有效阻止血清TRACP、DPD水平的激增,因此推测骨康方具有抑制破骨细胞活性,对破骨细胞凋亡起到调节作用,从而有效抑制骨吸收；
4.骨康方以补肾健脾活血为立方原则,该复方的组成从改善脏腑整体功能着手,以补脾益肾、改善微循环为手段,用来预防和治疗绝经后骨质疏松症,其作用机制可能是该方组成中含有类性激素样物质,维护体内激素代谢,对下丘脑-垂体-性腺轴的各个层次均有改善作用,进而通过抑制破骨细胞的骨吸收并促进成骨细胞的骨形成,从而恢复骨吸收与骨形成的偶联机制来实现的,是防治绝经后骨质疏松症的理想药物。
Objective
In order to disuse the effects of gukang on the bone Transformation of the postmenopausal osteoporosis, The clinical observation of retrain the bone high conversion rate by Gukang and calcium, and the influence of bone forms as well as the bone absorption target. The clinical observation and comparison of the effects of preparation prevention and the treatment menopause the osteoporosis by Gukang as well as calcium, To analysis the osteoporosis occurrence mechanism as well as the Chinese medicine application mechanism, fill up the clinical data of Gukang on the bone forms and the bone absorption.
Method
A total of 58 postmenopausal osteoporosis women diagnosed with the clinical examination and bone mineral density were Chosed, who were volunteered to join the clinical trials, According to the number of bone mineral density examination divided into two groups randomly, Gukang group and the control group, two group were given Publicity and education. FOR the control group were given Caltrate D film,1 #/day. GuKang Group were given to Prescription GuKang (1 dose/d) and Caltrate D film 1 #/day, the method of drug delivered was cyclic intermittent administration, which took three weeks straight, rest for 1 week. A course of 4 weeks for 6 cycles. Measured by bone mineral density and enzyme-linked immunosorbent assay before and after treatment, the level of serum Bone source alkaline phosphatases, osteocalcin, tartrate-resistant acid phosphatase, urinary deoxypyridinoline and urine creatinine, and treatment group compared with the test before and after the data, we take the bilateral side ofα<0.05 as statistically significant difference in standards.
Result
According to statistical results suggest:GuKang group and control group in age, weight, height, body mass index, menopausal age are compared, P> 0.05, there was no significant, the bone mineral density, and the leber of serum B-ALP, BGP, TrACP, DPD excretionof both Gukang group and control group before treatment compared, P> 0.05, there was no significant, indicated that it is reasonable and comparability according to the order of selection in case of randomized number between the two groups. GuKang group and the control group after treatment bone mineral density, the level of serum B-ALP comparison, P> 0.05 there was no significant, the level of serum BGP, TrACP, DPD excretion rate comparison P<0.01 there were distinguished significant. Bone mineral density before and after treatment of Gukang was not significant, before and after treatment B-ALP, BGP, TrACP, DPD excretion was significant difference. Control group, bone mineral density before and after treatment, TrACP, DPD excretion compared, P> 0.05, not significant, B-ALP before and after treatment comparison, P<0.05, statistically significant, before and after treatment BGPP<0.01 the was distinguished significant.
Conlusions
1. According to bone mineral density in selected cases when the sequence number randomized feasible, Gukang group and control group in age, weight, height, body mass index, menopausal age was not statistically significant, Gukang grop and control groups before treatment bone mineral density, B-ALP, BGP, TrACP, DPD excretion rate was not statistically significant between the two groups thatthey were comparable.
2. The control group before and after treatment bone mineral density, TrACP, DPD excretion rate was not statistically significant, before and after treatment, B-ALP were statistically significant. BGP concentration were significant differences in calcium therapy on bone mineral density, TRACP, DPD excretion not significant, can reduce the concentration of B-ALP and BGP levels, inhibit the bone high conversion, it can be used to prevent and treat postmenopausal osteoporosis.
3. GuKang group before and after treatment no significant in bone mineral density after treatment, B-ALP, BGP, TRACP, DPD excretion was significant difference in bone GuKang group and the control group after treatment bone mineral density, B-ALP was not significant After treatment, BGP, TRACP, DPD excretion was significant difference, indicating bone health to effectively inhibit bone of high conversion rate, can promote bone formation and reduce bone resorption, in the prevention and treatment of postmenopausal osteoporosis, the effect significantly superior in the control group.
骨质疏松症(osteoporosis, OP)是一种以低骨量和骨组织微结构破坏为特征,导致骨骼脆性增加和易发生骨折的全身性疾病,其发生机制包括衰老因素、激素调控、遗传因素、细胞因子、营养因素、物理因素、生活习惯等,骨质疏松症的筛查诊断指标有多种,由于低骨量是骨质疏松公认的最可靠的高危因素,骨质疏松症属代谢性骨病之一。骨代谢异常是由破骨细胞骨吸收活性与成骨细胞骨形成活性所构成的骨重建机制失去平衡所致,在骨重建过程中骨量过多流失,并损害骨结构,依据骨重建异常的病理可分为高转换型骨质疏松症和低转换型骨质疏松症。既往研究表明绝经后骨质疏松症属于高转换型,骨转换生化指标的变化与骨丢失的发生、程度及转归相一致,而且早于骨密度,骨转换生化指标反映的是整体的骨细胞活性,因此在预测及评估妇女绝经后的骨量变化及骨质疏松筛查方面有一定的实用价值,而且治疗绝经后骨质疏松症并非每一种药对每个患者都有效,而骨转换指标较骨密度能更早地反映出骨代谢对治疗的反应,能更早地预测患者的治疗效果,骨形成标记物常用血清骨特异性碱性磷酸酶(B-ALP)、骨钙素(BGP)指标,骨吸收标记物常用抗酒石酸酸性磷酸酶(TRACP)、尿脱氧吡啶啉(DPD)排泄率。根据所述及的临床症状及发病机理,骨质疏松症与“骨痹”“骨痿”等颇为相似。导师庄洪教授分析认为其中医发病机制为肾气肾精亏虚、脾胃功能失调、血瘀阻滞经脉,并以补肾健脾活血为法则,同所在研究单位研发骨康方,该复方的组成正是从改善脏腑整体功能着手,以补脾益肾、改善微循环为手段,用来预防和治疗绝经后骨质疏松症,其作用机制可能是该方组成中含有类性激素样物质,维护体内激素代谢,对下丘脑-垂体-性腺轴的各个层次均有改善作用,进而通过抑制破骨细胞的骨吸收并促进成骨细胞的骨形成,从而恢复骨吸收与骨形成的偶联机制来实现的,经临床观察和动物实验证实其具有抑制骨吸收和促进骨形成的双重作用,是防治绝经后骨质疏松症的理想药物。
目的
探讨补肾健脾活血法(骨康方)对绝经后骨质疏松患者骨转化的影响,临床观察骨康方以及钙剂能否有效抑制骨的高转化率,以及对骨形成和骨吸收指标的影响；临床观察骨康方以及钙剂能否预防和治疗绝经后骨质疏松,并且比较两者之间的疗效。对骨质疏松症的发生机理以及中医药的应用机理进行分析探讨,填补骨康方对骨吸收以及骨形成指标的临床数据,为进一步表明骨康方的临床有效性以及优越性。
方法
选择经骨密度测定及临床检查确诊为绝经后骨质疏松症患者且自愿加入临床实验研究,共58例,根据骨密度检查时的编号随机分为二组,即骨康组,对照组,两组均给予宣传教育,对照组给予口服钙尔奇D片,每日1次,1片／次。骨康组给予骨康(1剂／日)+钙尔奇D(每日1次,1片／次),给药方法采用循环间歇性给药,即连续服用3周,休息1周。4周为一疗程,连续6个疗程。采用双能X线骨密度仪测定患者治疗前后骨密度,采用酶联免疫法测定患者治疗前后血清骨碱性磷酸酶、骨钙素、抗酒石酸酸性磷酸酶、尿脱氧吡啶啉、尿肌酐,组间与各组治疗前后资料比较用t检验,取双侧α<0.05作为统计显著差异的标准。
结果
根据统计结果提示：骨康组与对照组年龄、体重、身高、体重指数、绝经年限之间比较,P>0.05,无统计学意义,骨康组与对照组治疗前骨密度、B-ALP、BGP、TRACP、DPD排泄率比较,P>0.05,无统计学意义,说明根据入选病例时骨密度的顺序号随机分组合理,两组之间具有可比性。骨康组与对照组治疗后骨密度、B-ALP比较,P>0.05无统计学意义,治疗后BGP、TRACP、DPD排泄率比较P<0.01具有显著性差异。骨康组治疗前后骨密度无统计学意义,治疗前后B-ALP、BGP、TRACP、DPD排泄率具有显著性差异。对照组治疗前后骨密度、TRACP、DPD排泄率比较,P>0.05,无统计学意义,治疗前后B-ALP浓度比较,P<0.05,具有统计学意义,治疗前后BGPP<0.01具有显著性差异。
结论
1.骨康方以及钙剂组在对患者的骨密度影响方面均无明显差异,但从骨密度的绝对值以及趋势来看,无论骨康方以及钙剂均能提高患者的骨密度,且骨康方组较钙剂组更为明显；
2.钙剂以及中药骨康均能调节血清BGP和B-ALP浓度,对成骨细胞的活性有一定的影响,骨康方配合钙剂较单纯钙剂组效果更为明显,能有效抑制血清ALP、BGP水平的快速升高,以保持适度的骨转换,趋于正常和平衡的骨代谢。中药骨康方可能是通过调节全身激素及骨髓中细胞因子,抑制代偿性增强的成骨细胞活性,使成骨细胞和破骨细胞活性趋于平衡；
3.单纯服钙剂不足以抑制骨吸收,降低骨转换,骨康方能有效阻止血清TRACP、DPD水平的激增,因此推测骨康方具有抑制破骨细胞活性,对破骨细胞凋亡起到调节作用,从而有效抑制骨吸收；
4.骨康方以补肾健脾活血为立方原则,该复方的组成从改善脏腑整体功能着手,以补脾益肾、改善微循环为手段,用来预防和治疗绝经后骨质疏松症,其作用机制可能是该方组成中含有类性激素样物质,维护体内激素代谢,对下丘脑-垂体-性腺轴的各个层次均有改善作用,进而通过抑制破骨细胞的骨吸收并促进成骨细胞的骨形成,从而恢复骨吸收与骨形成的偶联机制来实现的,是防治绝经后骨质疏松症的理想药物。
Objective
In order to disuse the effects of gukang on the bone Transformation of the postmenopausal osteoporosis, The clinical observation of retrain the bone high conversion rate by Gukang and calcium, and the influence of bone forms as well as the bone absorption target. The clinical observation and comparison of the effects of preparation prevention and the treatment menopause the osteoporosis by Gukang as well as calcium, To analysis the osteoporosis occurrence mechanism as well as the Chinese medicine application mechanism, fill up the clinical data of Gukang on the bone forms and the bone absorption.
Method
A total of 58 postmenopausal osteoporosis women diagnosed with the clinical examination and bone mineral density were Chosed, who were volunteered to join the clinical trials, According to the number of bone mineral density examination divided into two groups randomly, Gukang group and the control group, two group were given Publicity and education. FOR the control group were given Caltrate D film,1 #/day. GuKang Group were given to Prescription GuKang (1 dose/d) and Caltrate D film 1 #/day, the method of drug delivered was cyclic intermittent administration, which took three weeks straight, rest for 1 week. A course of 4 weeks for 6 cycles. Measured by bone mineral density and enzyme-linked immunosorbent assay before and after treatment, the level of serum Bone source alkaline phosphatases, osteocalcin, tartrate-resistant acid phosphatase, urinary deoxypyridinoline and urine creatinine, and treatment group compared with the test before and after the data, we take the bilateral side ofα<0.05 as statistically significant difference in standards.
Result
According to statistical results suggest:GuKang group and control group in age, weight, height, body mass index, menopausal age are compared, P> 0.05, there was no significant, the bone mineral density, and the leber of serum B-ALP, BGP, TrACP, DPD excretionof both Gukang group and control group before treatment compared, P> 0.05, there was no significant, indicated that it is reasonable and comparability according to the order of selection in case of randomized number between the two groups. GuKang group and the control group after treatment bone mineral density, the level of serum B-ALP comparison, P> 0.05 there was no significant, the level of serum BGP, TrACP, DPD excretion rate comparison P<0.01 there were distinguished significant. Bone mineral density before and after treatment of Gukang was not significant, before and after treatment B-ALP, BGP, TrACP, DPD excretion was significant difference. Control group, bone mineral density before and after treatment, TrACP, DPD excretion compared, P> 0.05, not significant, B-ALP before and after treatment comparison, P<0.05, statistically significant, before and after treatment BGPP<0.01 the was distinguished significant.
Conlusions
1. According to bone mineral density in selected cases when the sequence number randomized feasible, Gukang group and control group in age, weight, height, body mass index, menopausal age was not statistically significant, Gukang grop and control groups before treatment bone mineral density, B-ALP, BGP, TrACP, DPD excretion rate was not statistically significant between the two groups thatthey were comparable.
2. The control group before and after treatment bone mineral density, TrACP, DPD excretion rate was not statistically significant, before and after treatment, B-ALP were statistically significant. BGP concentration were significant differences in calcium therapy on bone mineral density, TRACP, DPD excretion not significant, can reduce the concentration of B-ALP and BGP levels, inhibit the bone high conversion, it can be used to prevent and treat postmenopausal osteoporosis.
3. GuKang group before and after treatment no significant in bone mineral density after treatment, B-ALP, BGP, TRACP, DPD excretion was significant difference in bone GuKang group and the control group after treatment bone mineral density, B-ALP was not significant After treatment, BGP, TRACP, DPD excretion was significant difference, indicating bone health to effectively inhibit bone of high conversion rate, can promote bone formation and reduce bone resorption, in the prevention and treatment of postmenopausal osteoporosis, the effect significantly superior in the control group.
引文
[1]张娜,曹艳,史亦丽.骨质疏松症治疗药物应用分析[J].中国医院用药评价与分析,2006,6(5)：286-290.
[2]赵文国,张柳,程爱国,等.骨质疏松症诊断的新进展[J].2002,18(12)：1065-1066.
[3]沈霖,杨艳萍,谢晶,等.国人原发性骨质疏松症诊断标准研究[J].中国中医骨伤科杂志,2003,11(1)：1-4.
[4]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[J].中华骨科杂志,2001,21(5)：275.
[5]沈铁城,林华.骨质疏松现代诊疗[M].南京：江苏科学技术出版社,2001.3.
[6]李宁华,张大新,李恩,等.华北部分地区汉族中老年人群骨质疏松症患病率调查[J].中国预防医学杂志,2001,2(2)：97.
[7]张伏元,邓展生,伍峰.原发性骨质疏松患病率调查[J].中国现代医学杂志,2003,13(1)：48-52.
[8]区品中.广州地区中老年人群骨量减少及骨质疏松患病率的调查[J].中国骨质疏松杂志,2002,8(4)：314-318.
[9]Kanis JA, Johnell 0, Oden A, et al. Ten year probabilities of esteoporotic fractures according to BMD and diagnostic thresholds [J]. Osteoporos Int,2001, 12(12):989-995.
[10]Almeida M, Han L, Martin-Millan M, et al. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids[J].J Biol Chem,2007,282(37):27285-27297.
[11]Lozo P, Krpan D, Krvavica A, et al. Bone histology in postmenopausal osteoporosis-variations in cellular activity[J].Acta MED Croatica,2004, 58(1):5-11.
[12]Inanir A, Ozoran K, Tutkak H, et al.The effects of calcitriol therapy on serum interleukin-1, interleukin-6 and tumournecrosis factor-alpha concentrations in post-menopausal patients with osteoporosis[J]. J Int Med Res,2004,32(6):570-582.
[13]Desai MP, Bhanuprakash KV, Khatkhatay MI, et al. Age-related changes in bone turnover markers and ovarianhormones in premenopausal and postmenopausal Indian women [J]. J Clin Lab Anal,2007,21(2):55-60.
[14]D' Amelio P, Grimaldi A, Pescarmona GP, et al. Spontaneous osteoclast formation from peripheral blood mononuclear cells in postmenopausal osteoporosis[J].FASEB J,2005,19(3):410-412.
[15]Nakamura T, Imai Y, Matsumoto T, et al. Estrogen Prevents Bone Loss via Estrogen Receptor alpha and Induction of Fas Ligand in Osteoclasts[J]. Cell, 2007,130(5):811-823.
[16]杨力,蔡德鸿,汤灵丽.绝经后骨质疏松与IGF-1及相关骨代谢指标关系的研究[J].广东医学,2005,26(5)：624-626.
[17]苏欣,廖二元,朱旭萍,等.雌二醇对人成骨细胞护骨素、护骨素配体及其相关因子的调节[J].中华老年医学杂志,2004,23(3)：154-155.
[18]Hong L, Colpan A, Peptan IA. Modulations of 17-beta estradiol on osteogenic and adipogenic differentiations of human mesenchymal stem cells[J]. Tissue Eng,2006,12(10):2747-2753.
[19]Mann V, Huber C, Kogianni G, et al. The antioxidant effect of estrogen and Selective Estrogen Receptor Modulators in the inhibition of osteocyte apoptosis in vitro[J]. Bone,2007,40(3):674-684.
[20]李平生,彭朝津,钱红,等.住院老年男性26例骨密度与雄性激素关系分析[J].中国临床康复,2003,7(5)：741.
[21]Liegibel UM, Sommer U, Boercsoek I, et al. Androgen receptor isoforms AR-A and AR-B display functional diferences in cultured human bone cells and genital skin fibroblasts[J]. Steroids,2003,68(14):1179-1187.
[22]Higano CS. Side effects of androgen deprivation therapy:monitoring and minimizing toxicity [J]. Urology,2003,61(Suppl 1):32-38.
[23]Wolf OT, Preut R, Hellhammer DH, et al. Testosterone and cognition elderly men:a single testosteron injection blocks the practice effect in verbal fluency,but has no efect on spatial or verbal memory [J]. Biol Psychiatry, 2000,47(7):650-654.
[24]Huang CL, Sun L, Moonga BS, et al. Molecular physiology and pharmacology of calcitonin[J].Cell Mol Biol,2006,52(3):33-43.
[25]Bruyere O, Malaise O, Neuprez A, et al. Prevalence of vitamin D inadequacy in European postmenopausal women [J]. CurrMed Res Opin,2007,23 (8):1939-1944.
[26]Ongphiphadhanakul B.Osteoporosis:the role of genetics and the environment[J]. Forum Nutr,2007,60:158-167.
[27]Ozmen B, Kirmaz C, Aydin K, et al. Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNF-alpha, TGF-beta1 and bone turnover markers in the treatment of postmenopausal osteoporosis [J]. Eur Cytokine Netw,2007,18(3):148-153.
[28]Coronado-Zarco R, Diez-Garcia Mdel P, Chavez-Arias D, et al. Correlation of age, IGF-1 serum levels, muscular mass index and their influence as determinants of isokinetic variables in patients with osteoporosis[J]. Cir Cir,2005,73(6):457-463.
[29]Parkhouse WS, Coupland DC, Li C, et al. IGF-1 bioavailability is increased by resistance training in older women with low bone mineral density[J]. Mech Ageing Dev,2000,113(2):75-83
[30]Lin JT, Lane JM. Prevention of hip fractures:medical and Nonmedical Management[J]. Instr Course Lect,2004,53:417-425.
[31]Horiuchi T, Onouchi T, Takahashi M, et al. Effect of soy protein on bone metabolism in postmenopausal Japanesewomen[J]. Osteoporos Int,2000, 11(8):721-724.
[32]Wong PK, Christie JJ, Wark JD. The effects of smoking on bone health[J].Clin Sci (Lond),2007,113(5):233-241.
[33]Torricelli P, Fini M, Giavaresi G, et al. Intermittent exposure vapor affects osteoblast behaviour more severely the estrogen deficiency does in vitro study on rat osteoblasts[J] Toxicology,2007,237(1-3):168-176.
[34]Saitoglu M, Ardicoglu 0, Ozqocmen S, et al.Osteoporosis ris factors and association with somatotypes in males[J]. Arc Med Res,2007,38(7):746-751.
[35]Ross PD, Knowllon W. Rapid bone loss is associaled with increased leves of biochemical markers [J]. J Bone Miner Res,1998,13:297-302.
[36]杨伟民, 邵斌.骨代谢生化指标与骨质疏松症[J].中国骨质疏松杂志,2004,1(10)：118-121.
[37]吴文苑.骨型碱性磷酸酶的检测方法和临床应用[J].国外医学·临床生物化学与检验学分册.1999,20(2)：64-65
[38]田玉慧,娄静,李万里,等.麦胚提取物对去卵巢大鼠骨密度和矿物质的作用[J].新乡医学院学报,2003,20(3)：153-155
[39]黄干等,抗酒石酸酸性磷酸酶与骨吸收,国外医学生理、病理科学与临床分册1998,18(1)
[40]向青,苏楠.第二代骨吸收生化标志物-血清抗酒石酸酸性磷酸酶5b的临床研究[J].中国骨质疏松杂志,2002,8：331.
[41]Hallen JM, Tiitinen SL, Ylipahkala H, et al. Tart rate resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption[J]. Clin Lab 2006,52 (9210):499.
[42]赵治友,邬亚军.骨质疏松症的中医辨证思路与治法研究[J].浙江中医药大学学报.2007；31(3)：275-276
[43]中医研究院西苑医院主编.岳美中医话集[M].中医古籍出版社.1984：46
[44]庄洪,梁祖建.从瘀论治原发性骨质疏松症研究态势评析[J].中医正骨.2006；18(2)：69-71
[45]王全权,陈海林,宗芳,等.补骨脂复方制剂干预绝经后骨质疏松症的作用[J].中国临床康复.2006,10(35)：145-147
[46]朱志刚,宋利格,张秀珍.淫羊藿总黄酮对去卵巢大鼠骨组织Ⅰ型胶原代谢及组织蛋白酶K表达的影响[J].中华内分泌代谢杂志,2006,22(3)：213-217
[47]YIN Xiao-xue, CHEN Zhong-qiang, LIU Zhong-jun, et al. Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2[J]. Chin Med J,2007,120(3):204-210
[48]王晓敏,王建红,伍庆华,等.菟丝子黄酮对去势雌性大鼠血清雌激素水平和血管平滑肌细胞的影响[J].天津医药,2005,33(10)：650-652
[49]吴波,付玉梅.肉苁蓉总苷对亚急性衰老小鼠抗脂质过氧化作用的研究[J].中国药理学通报,2005,21(5)：639
[50]陈华庭,王虎,郑菁,等.黄芪总黄酮提取物对维甲酸所致大鼠骨质疏松的影响[J].中国药师,2005,8(11)：895-897
[51]盛莉,邢国胜,王毅,等.熟地对去卵巢大鼠骨代谢生化指标及骨密度的影响[J].中国骨质疏松杂志,2006,12(5)：496-498
[52]中国老年学学会骨质疏松委员会骨质疏松诊断标准学科组.中国人骨质疏松症建议诊断标准(第二稿)[J].中国骨质疏松杂志.2000；6(1)：1-3
[53]Nguyen TV, Pocock N, Eisman JA1[Jl. J Clin Densitom,2000, 3(2):1072-1191
[54]骨康及含药血清中类性激素样物质含量的测定林一峰、魏合伟、蔡桦等,中医药学刊,2003,21(5)：663-664
[55]刘海金,陈超.刘庆思教授治疗骨质疏松症经验介绍.新中医,2007,39(5)：14
[2]赵文国,张柳,程爱国,等.骨质疏松症诊断的新进展[J].2002,18(12)：1065-1066.
[3]沈霖,杨艳萍,谢晶,等.国人原发性骨质疏松症诊断标准研究[J].中国中医骨伤科杂志,2003,11(1)：1-4.
[4]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[J].中华骨科杂志,2001,21(5)：275.
[5]沈铁城,林华.骨质疏松现代诊疗[M].南京：江苏科学技术出版社,2001.3.
[6]李宁华,张大新,李恩,等.华北部分地区汉族中老年人群骨质疏松症患病率调查[J].中国预防医学杂志,2001,2(2)：97.
[7]张伏元,邓展生,伍峰.原发性骨质疏松患病率调查[J].中国现代医学杂志,2003,13(1)：48-52.
[8]区品中.广州地区中老年人群骨量减少及骨质疏松患病率的调查[J].中国骨质疏松杂志,2002,8(4)：314-318.
[9]Kanis JA, Johnell 0, Oden A, et al. Ten year probabilities of esteoporotic fractures according to BMD and diagnostic thresholds [J]. Osteoporos Int,2001, 12(12):989-995.
[10]Almeida M, Han L, Martin-Millan M, et al. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids[J].J Biol Chem,2007,282(37):27285-27297.
[11]Lozo P, Krpan D, Krvavica A, et al. Bone histology in postmenopausal osteoporosis-variations in cellular activity[J].Acta MED Croatica,2004, 58(1):5-11.
[12]Inanir A, Ozoran K, Tutkak H, et al.The effects of calcitriol therapy on serum interleukin-1, interleukin-6 and tumournecrosis factor-alpha concentrations in post-menopausal patients with osteoporosis[J]. J Int Med Res,2004,32(6):570-582.
[13]Desai MP, Bhanuprakash KV, Khatkhatay MI, et al. Age-related changes in bone turnover markers and ovarianhormones in premenopausal and postmenopausal Indian women [J]. J Clin Lab Anal,2007,21(2):55-60.
[14]D' Amelio P, Grimaldi A, Pescarmona GP, et al. Spontaneous osteoclast formation from peripheral blood mononuclear cells in postmenopausal osteoporosis[J].FASEB J,2005,19(3):410-412.
[15]Nakamura T, Imai Y, Matsumoto T, et al. Estrogen Prevents Bone Loss via Estrogen Receptor alpha and Induction of Fas Ligand in Osteoclasts[J]. Cell, 2007,130(5):811-823.
[16]杨力,蔡德鸿,汤灵丽.绝经后骨质疏松与IGF-1及相关骨代谢指标关系的研究[J].广东医学,2005,26(5)：624-626.
[17]苏欣,廖二元,朱旭萍,等.雌二醇对人成骨细胞护骨素、护骨素配体及其相关因子的调节[J].中华老年医学杂志,2004,23(3)：154-155.
[18]Hong L, Colpan A, Peptan IA. Modulations of 17-beta estradiol on osteogenic and adipogenic differentiations of human mesenchymal stem cells[J]. Tissue Eng,2006,12(10):2747-2753.
[19]Mann V, Huber C, Kogianni G, et al. The antioxidant effect of estrogen and Selective Estrogen Receptor Modulators in the inhibition of osteocyte apoptosis in vitro[J]. Bone,2007,40(3):674-684.
[20]李平生,彭朝津,钱红,等.住院老年男性26例骨密度与雄性激素关系分析[J].中国临床康复,2003,7(5)：741.
[21]Liegibel UM, Sommer U, Boercsoek I, et al. Androgen receptor isoforms AR-A and AR-B display functional diferences in cultured human bone cells and genital skin fibroblasts[J]. Steroids,2003,68(14):1179-1187.
[22]Higano CS. Side effects of androgen deprivation therapy:monitoring and minimizing toxicity [J]. Urology,2003,61(Suppl 1):32-38.
[23]Wolf OT, Preut R, Hellhammer DH, et al. Testosterone and cognition elderly men:a single testosteron injection blocks the practice effect in verbal fluency,but has no efect on spatial or verbal memory [J]. Biol Psychiatry, 2000,47(7):650-654.
[24]Huang CL, Sun L, Moonga BS, et al. Molecular physiology and pharmacology of calcitonin[J].Cell Mol Biol,2006,52(3):33-43.
[25]Bruyere O, Malaise O, Neuprez A, et al. Prevalence of vitamin D inadequacy in European postmenopausal women [J]. CurrMed Res Opin,2007,23 (8):1939-1944.
[26]Ongphiphadhanakul B.Osteoporosis:the role of genetics and the environment[J]. Forum Nutr,2007,60:158-167.
[27]Ozmen B, Kirmaz C, Aydin K, et al. Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNF-alpha, TGF-beta1 and bone turnover markers in the treatment of postmenopausal osteoporosis [J]. Eur Cytokine Netw,2007,18(3):148-153.
[28]Coronado-Zarco R, Diez-Garcia Mdel P, Chavez-Arias D, et al. Correlation of age, IGF-1 serum levels, muscular mass index and their influence as determinants of isokinetic variables in patients with osteoporosis[J]. Cir Cir,2005,73(6):457-463.
[29]Parkhouse WS, Coupland DC, Li C, et al. IGF-1 bioavailability is increased by resistance training in older women with low bone mineral density[J]. Mech Ageing Dev,2000,113(2):75-83
[30]Lin JT, Lane JM. Prevention of hip fractures:medical and Nonmedical Management[J]. Instr Course Lect,2004,53:417-425.
[31]Horiuchi T, Onouchi T, Takahashi M, et al. Effect of soy protein on bone metabolism in postmenopausal Japanesewomen[J]. Osteoporos Int,2000, 11(8):721-724.
[32]Wong PK, Christie JJ, Wark JD. The effects of smoking on bone health[J].Clin Sci (Lond),2007,113(5):233-241.
[33]Torricelli P, Fini M, Giavaresi G, et al. Intermittent exposure vapor affects osteoblast behaviour more severely the estrogen deficiency does in vitro study on rat osteoblasts[J] Toxicology,2007,237(1-3):168-176.
[34]Saitoglu M, Ardicoglu 0, Ozqocmen S, et al.Osteoporosis ris factors and association with somatotypes in males[J]. Arc Med Res,2007,38(7):746-751.
[35]Ross PD, Knowllon W. Rapid bone loss is associaled with increased leves of biochemical markers [J]. J Bone Miner Res,1998,13:297-302.
[36]杨伟民, 邵斌.骨代谢生化指标与骨质疏松症[J].中国骨质疏松杂志,2004,1(10)：118-121.
[37]吴文苑.骨型碱性磷酸酶的检测方法和临床应用[J].国外医学·临床生物化学与检验学分册.1999,20(2)：64-65
[38]田玉慧,娄静,李万里,等.麦胚提取物对去卵巢大鼠骨密度和矿物质的作用[J].新乡医学院学报,2003,20(3)：153-155
[39]黄干等,抗酒石酸酸性磷酸酶与骨吸收,国外医学生理、病理科学与临床分册1998,18(1)
[40]向青,苏楠.第二代骨吸收生化标志物-血清抗酒石酸酸性磷酸酶5b的临床研究[J].中国骨质疏松杂志,2002,8：331.
[41]Hallen JM, Tiitinen SL, Ylipahkala H, et al. Tart rate resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption[J]. Clin Lab 2006,52 (9210):499.
[42]赵治友,邬亚军.骨质疏松症的中医辨证思路与治法研究[J].浙江中医药大学学报.2007；31(3)：275-276
[43]中医研究院西苑医院主编.岳美中医话集[M].中医古籍出版社.1984：46
[44]庄洪,梁祖建.从瘀论治原发性骨质疏松症研究态势评析[J].中医正骨.2006；18(2)：69-71
[45]王全权,陈海林,宗芳,等.补骨脂复方制剂干预绝经后骨质疏松症的作用[J].中国临床康复.2006,10(35)：145-147
[46]朱志刚,宋利格,张秀珍.淫羊藿总黄酮对去卵巢大鼠骨组织Ⅰ型胶原代谢及组织蛋白酶K表达的影响[J].中华内分泌代谢杂志,2006,22(3)：213-217
[47]YIN Xiao-xue, CHEN Zhong-qiang, LIU Zhong-jun, et al. Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2[J]. Chin Med J,2007,120(3):204-210
[48]王晓敏,王建红,伍庆华,等.菟丝子黄酮对去势雌性大鼠血清雌激素水平和血管平滑肌细胞的影响[J].天津医药,2005,33(10)：650-652
[49]吴波,付玉梅.肉苁蓉总苷对亚急性衰老小鼠抗脂质过氧化作用的研究[J].中国药理学通报,2005,21(5)：639
[50]陈华庭,王虎,郑菁,等.黄芪总黄酮提取物对维甲酸所致大鼠骨质疏松的影响[J].中国药师,2005,8(11)：895-897
[51]盛莉,邢国胜,王毅,等.熟地对去卵巢大鼠骨代谢生化指标及骨密度的影响[J].中国骨质疏松杂志,2006,12(5)：496-498
[52]中国老年学学会骨质疏松委员会骨质疏松诊断标准学科组.中国人骨质疏松症建议诊断标准(第二稿)[J].中国骨质疏松杂志.2000；6(1)：1-3
[53]Nguyen TV, Pocock N, Eisman JA1[Jl. J Clin Densitom,2000, 3(2):1072-1191
[54]骨康及含药血清中类性激素样物质含量的测定林一峰、魏合伟、蔡桦等,中医药学刊,2003,21(5)：663-664
[55]刘海金,陈超.刘庆思教授治疗骨质疏松症经验介绍.新中医,2007,39(5)：14