骨碎补总黄酮对老年性骨质疏松症成骨作用影响的临床与实验研究
|
摘要
目的:
从理论角度分析总结老年性骨质疏松症的发病原因,并通过实验研究探讨骨碎补总黄酮对骨髓基质细胞脂质化的影响,以及对成骨细胞衰变和凋亡的影响,从临床角度观察其治疗老年性骨质疏松症的效果,为临床应用提供科学理论依据。
方法:
临床研究:选择股骨近端BMD较同性别年轻成人均值低2.5SD以上,诊断为老年性骨质疏松症者70例。采用随机对照的方法,分为治疗组(口服强骨胶囊)36例,对照组(口服钙尔奇D)34例,依据对腰背痛及腰痛综合评分进行动态观察;依据“疼痛VAS线段分级法”对腰背痛(静止痛、翻身痛、久坐痛、起身痛、弯腰痛、步行痛、睡眠痛、叩击痛、压痛)进行量化动态观察;依据“Barthel指数评定法”对老年性骨质疏松症日常生活活动能力(ADL)进行观察;采用双能X线骨密度仪对腰椎(L_2-L_4)、股骨近端各部位:股骨颈(Neck)、股骨三角区(Ward)、股骨粗隆(Troch)进行骨密度(BMD)定量检测;应用放射免疫法对骨转换指标进行测定,骨形成指标:骨钙素(BGP)、Ⅰ型前胶原氨基端前肽(PINP);骨吸收指标:Ⅰ型胶原交联羧基末端肽(ICTP)等,评价骨碎补总黄酮治疗老年性骨质疏松症的临床效果。
实验研究:通过WST-8分析骨碎补总黄酮含药血清对大鼠骨髓基质细胞活性的影响;以地塞米松诱导骨髓基质细胞脂质化后,建立脂肪细胞与骨髓基质细胞的共培养体系,用骨碎补总黄酮含药血清干预后,以TUNEL法检测骨髓基质细胞的凋亡情况;采用三丁基过氧化氢(t-BHP)体外诱导大鼠成骨细胞衰老,用骨碎补总黄酮含药血清干预后,以SA-β-半乳糖苷酶(Se-nescence associatedβ-galactosidase)化学染色,观察细胞衰老情况;将大鼠成骨细胞培养于含有肿瘤坏死因子-α(TNF-α)或骨碎补总黄酮加TNF-α培养基中后,通过荧光染色细胞核DNA及电镜下超微结构观察,检测成骨细胞凋亡情况。
结果:
1.“疼痛六点行为评分法(BRS-6)”观察结果显示,治疗前老年性骨质疏松症患者的腰背痛及腰痛多在Ⅲ～Ⅴ级之间,疼痛无法忽视,对日常生活有一定的影响。运用强骨胶囊(骨碎补总黄酮)治疗3个月后疼痛分级多降至到Ⅰ～Ⅱ级,自觉疼痛基本消失。说明骨碎补总黄酮在一定程度上能够改善老年性骨质疏松症引起的腰背痛及腰痛,缓解疼痛的幅度以治疗的前3个月最为明显。
2.“疼痛VAS线段分级法”观察结果显示,治疗前静止时腰背痛、久坐时腰背痛、步行时腰背痛均呈现中度疼痛,翻身时腰背痛、起身时腰背痛、弯腰时腰背痛、腰背压痛与叩击痛多表现重度疼痛,而以弯腰时腰背痛、腰背叩击痛尤为显著,部分病人腰背痛对睡眠会有一定影响。运用骨碎补总黄酮治疗3个月后,各种行为方式引起的腰背痛均有不同程度的改善,其中治疗1个月后腰背痛对睡眠的影响较小,治疗2个月后多数静止痛、久坐痛基本消失,治疗3个月多数翻身痛、起身痛、步行痛、压痛可缓解,但部分病人仍然呈现出一定程度的弯腰痛和腰背叩击痛。由此可见,骨碎补总黄酮对老年性骨质疏松症病人静态生活方式出现的腰背痛改善迅速且明显,对动态生活方式引起腰背痛加重,以及外界干预加重的腰背痛也有一定的作用,但相对较慢。
3.“Barthel指数评定法”对日常生活活动能力(ADL)进行观察结果显示:治疗前多数病人Barthel指数评分为60～40分,表现中度残疾,有功能障碍,生活需要帮助;治疗3个月后积分可达到90分以上,生活基本自理,生活独立性有一定程度的改善,生活质量有很大提高。
4.双能X线骨密度仪对老年性骨质疏松症腰椎(L_2-L_4)、股骨近端各部位:股骨颈(Neck)、股骨三角区(Ward)、股骨粗隆(Troch)进行应用骨碎补总黄酮治疗前后骨密度(BMD)定量检测结果表明,应用骨碎补总黄酮治疗6个月后各部位BMD均有一定程度的升高;与对照组(钙尔奇D)相比,除外腰椎(L_2-L_4)的骨密度改善程度无差异,骨碎补总黄酮的治疗效果更为明显,二者对比,有显著性差异。说明骨碎补总黄酮对老年性骨质疏松症具有提高整体骨量的作用,同时能够提高股骨近端骨强度,预防髋部骨折。
5.骨代谢标志物检测结果表明,老年性骨质疏松症BGP、PINP比较正常成年人均有一定程度降低,说明老年性骨质疏松症成骨细胞功能衰退,合成胶原减少,成骨能力较弱;运用骨碎补总黄酮治疗6个月后,BGP、PINP均有一定程度上升,说明骨碎补总黄酮具有促进低转换型骨质疏松症骨胶原的合成,提高骨转换,增加骨形成等作用。老年性骨质疏松症ICTP比较正常成年人有一定程度升高,说明老年性骨质疏松症骨溶解增加,骨吸收相对较快。运用骨碎补总黄酮治疗6个月后,ICTP有一定程度上降低,说明骨碎补总黄酮具有减缓低转换型骨质疏松症骨吸收状况的功效。
6.骨碎补总黄酮含药血清对大鼠骨髓基质细胞活性的影响研究结果表明,经骨碎补总黄酮干预后大鼠骨髓基质细胞数量显著增加,说明骨碎补总黄酮能够提高大鼠骨髓基质细胞的活性,并具有促进其增殖分裂的作用。
7.骨碎补总黄酮对TNF-α诱导的大鼠成骨细胞凋亡的抑制作用研究结果表明,在用空白血清培养的成骨细胞中加入TNF-α,可见到成骨细胞出现凋亡征象,凋亡的成骨细胞显著增多;而用骨碎补总黄酮含药血清培养的成骨细胞,凋亡细胞明显减少,虽然仍有细胞凋亡的形态改变,但可部分对抗TNF-α所致的成骨细胞凋亡。
8.骨碎补总黄酮含药血清对脂质化大鼠骨髓基质细胞凋亡的保护作用研究结果表明,脂肪细胞能够诱导骨髓基质细胞的凋亡,用骨碎补总黄酮含药血清干预后,凋亡细胞明显减少,说明骨碎补总黄酮含药血清对脂质化大鼠骨髓基质细胞凋亡具有保护作用。
9.骨碎补总黄酮对大鼠成骨细胞衰老的影响研究表明,经t-BHP处理后的成骨细胞SA-β-半乳糖苷酶的细胞化学染色阳性的细胞数明显增多,而用骨碎补总黄酮干预的衰老细胞明显减少,说明骨碎补总黄酮含药血清对t-BHP诱导的大鼠成骨细胞衰老具有保护作用。
结论:
1.随着人类寿命的延长和人口老龄化,老年性骨质疏松症的发病率逐渐增加,严重危害着老年人的健康和生命。
2.老年性骨质疏松症是机体自然衰退、老化过程的组成部分,骨髓基质细胞分化方向改变和成骨细胞的生物学功能衰退是其发病的细胞病理学基础,而五脏虚损和气血功能紊乱与其发病密切相关,其中肾虚为其核心病机。
3.临床研究表明:骨碎补总黄酮具有促进老年性骨质疏松症骨胶原的合成,提高骨转换,增加骨形成,减缓骨吸收状况等作用,进而提高老年性骨质疏松的整体骨量,缓解腰背痛,提高股骨近端骨强度,预防髋部骨折,提升独立性生活水准,全面提高老年性骨质疏松症患者的生命质量。
4.实验研究表明:骨碎补总黄酮能够提高大鼠骨髓基质细胞的活性,促进其增殖分裂,并对脂质化大鼠骨髓基质细胞凋亡具有保护作用,而且骨碎补总黄酮含药血清对TNF-α诱导的大鼠成骨细胞凋亡和t-BHP诱导的大鼠成骨细胞衰老均具有一定的保护作用。实验研究结果说明,骨碎补总黄酮对增强老年性骨质疏松症成骨作用具有重要的意义。
Objective:
From the theoretical angle,to analyze and summarize the morbility reason of Senile Osteoporosis,to approach the effect of the flavone of rhizome drynaria on the lipidision of marrow stroma cell,as well as the senescence and apoptosis of osteoblast through the experimental study;from the clinical angle,to observe the clinical effect of the flavone of rhizome drynania on Senile Osteoporosis,to supply scientific theory basis for clinical application.
Methods:
Clinical study:70 patients with Senile Osteoporosis who were depended the diagnostic criteria,were divided into two groups randomly,36 patients in treat group (treated with the Qianggu capsule);34 patients in control group(treated with Caltrate D 600 chew tablet).Appraised the clinical effect of the flavone of rhizome drynania on Senile Osteoporosis,according to the dynamic observation on integrative scores of lumbodorsal pain and lumbodynia,"VAS section grading method" on lumbodynia, "Barthel index rating method" on ADL,detected BMD on anterior-posterior position lumbar2～4 vertebra body and proximate of femur including neck/ward/troch,and determined the index of bone transition including BGP/PINP/ICTP through the radioimmunity method before and after treated half a year,then contrast intragroup and selfgroup.Depending on the standard of curative effect,contrast the difference of curative effect between two groups.
experimental study:The effect of flavone of rhizome drynaria's serum in blood on cytoactive of marrow stroma cell of rats from analyse of WST-8.After dexamethasone induced lipidsion of marrow stroma cell,based the co-culture system of cell and marrow stroma cell.we use TUNEL standard detect the marrow stroma cells' apotosis,after intervened of flavone of rhizome drynaria's serum.Osteoblast senescence of rats by we uesd t-BHP induce in vitro,after we used the flavone of rhizome drynaria's serum intervene,Se-nescence associatedβ-galactosidase chemi-staining, observe the cell senescence.To detect the osteoblast apoptosis,after cultured rats' osteoblast in the medium including TNF-a or the the flavone of rhizome drynaria and TNF-a,by fluorescence staining DNA of nucleus,and observing ultrastructure under electron microscope.
Results:
1.The observation results of 6-points Behavioural Rating Scale(BRS-6) displayed,the lumbodosal pain and lumbodynia with pretherapy SOP patients nearly were three or four degree,ignored impossible.There is several impact to daily living.The lumbodosal pain and lumbodynia lowered to one or tow degree after 3 months treated by the flavone of rhizome drynaria,the aware pain vanished.To illustrate the flavone of rhizome drynaria can extently amend the lumbodosal pain and lumbodynia with SOP,the pain obviously released after 3 months.
2.The observation results of "VAS section grading method" displayed,the lumbodynia showed midrange pain while rest/prolonged sitting/walking,and heavy-range pain while to turn the body over/to get up/bend from the waist/tenderness/percussion pain before treated,is especial significance while /to turn the body over/ percussion pain.A piece of patients' lumbodynia impacted their sleep.Various kinds of lumbodynia amended diversity extently through the flavone of rhizome drynaria treated after 3 months.After 1 month,the effect of lumbodynia on sleep is extremely trifling;after 2 months,the majority of rest and prolonged sitting pains nearly vanished;after 3 months,the majority of pains while to turn the body over/to get up/bend from the waist/tenderness/percussion pain can amend,but a piece of patients still showed the pain that bend from the waist and the percussion pain.From that to illustrate the flavone of rhizome drynaria can quickly and obviously amend the lumbodynia that SOP patients showed in static life style,but amend slowly in dynamic life style and surrounding intervention.
3.The observation results of "Barthel index rating method" on ADL displayed,the majority of patients' scores were 60～40 before treated,their life with moderate disability and dysfunction need help.After 3 months,the scores can achieve above 90,life nearly self cared,living independence amended extently,quality of life improved quietly.
4.The results that detected BMD on anterior-posterior position lumbar2～4 vertebra body and proximate of femur including neck/ward/troch displayed,all positions' BMD improved extently through treated by the flavone of rhizome drynaria after 6 months.The treat group has more conspicuous therapeutic efficacy than control group,there is a significant difference between the two groups,except the BMD on anterior-posterior position lumbar2～4 vertebra body.To illustrate that the flavone of rhizome drynaria can improve proximate of femur bone strength,and prevent fracture of hip.
5.The results that determined bone metabolism maker displayed,the SOP patients' BGP and PINP lower than normal adults,to illustrate that the SOP patients' osteoblast function decayed,synthesis collagen decreased,and bone formation capability weaken.After 6 months treated,BGP and PINP all upgraded extently,to illustrate that the flavone of rhizome drynaria can promote collagen synthesis, improve bone transition,and increase bone formation.The SOP patients' ICTP more advanced than normal adults,to illustrate that the SOP patients' osteolysis increased and bone resorption was more quickly.After 6 months treated,the SOP patients' ICTP lowered extently,to illustrate that the flavone of rhizome drynaria can delay the bone resorption.
6.The study results that the effect of flavone rhizome drynaria's serum on cytoactive of marrow stroma cell of rats indicated,the marrow stroma cell's quantity significant increased after intervened of flavone of rhizome drynaria's serum in,to illustrate that the flavone of rhizome drynaria can improve the cytoactive of marrow stroma cell of rats and promote its multiplicative division.
7.The study results that the depressant action of flavone rhizome drynaria's serum to osteoblast apoptosis of rats induced by TNF-a indicated,osteoblast cultured in vacant serum adding TNF-a showed apoptotic signs,and the quantity of apoptotic osteoblast significant increased.Osteoblast cultured in flavone rhizome drynaria's serum that its apoptotic significant decreased,although has the chang of apoptotic morphous,also can partially antagnoise osteoblast apoptosis with TNF-a.
8.The study results that the protection of flavone rhizome drynaria's serum to apoptosis of lipidsion marrow stroma cell of rats indicated,adipocyte can induce apoptosis of marrow stroma cell,and it significant decreased after intervened of flavone of rhizome drynaria's serum,to illustrate that the flavone of rhizome drynaria can protect the apoptosis of lipidsion marrow stroma cell of rats.
9.The study results that the effect of flavone rhizome drynaria's serum on osteoblast senescence of rats indicated,quantity of osteoblast Se-nescence associatedβ-galactosidase which cytochmical staining positive increased obviously after induced by t-BHP,but the quantity of osteoblast senescence decreased obviously,after intervened of flavone of rhizome drynaria's serum,to illustrate that the flavone of rhizome drynaria can protect the osteoblast senescence of rats induced by t-BHP.
Conclusions:
1.The attack rate of SOP is gradually increasing with the mankind life extending and population aging,seriously jeopardizing the aged health and life.
2.SOP is ingredient of the organism natural retrogression and aging process.Its pathogenetic cell pathology is marrow stroma cells' different direction changing and osteoblastics' biological function decaying,as well as,is intimate correlated with five viscera consumptive disease and Qi-blood functional disorder,renal deficiency is the core pathogenesis of that.
3.Clinical study indicated:the flavone of rhizome drynaria can promote collagen synthesis,improve bone transition,increase bone formation,delay bone resorption, furthermore,improve SOP patients' integer bone mass and proximate of femur bone strength,and prevent fracture of hip.Eventually,the level of living independence amended and the quality of life improved overall.
4.Experimental study indicated:the flavone of rhizome drynaria can improve the cytoactive of marrow stroma cell of rats,promote its multiplicative division,and protect the marrow stroma cells' apotosis with lipidsion.The flavone of rhizome drynaria's serum can extently protect the osteoblast apoptosis of rats induced by TNF-a and the osteoblast senescence of rats induced by t-BHP.The results of empirical study to illustrate that the flavone of rhizome drynaria has considerable significance to improve the bone formation action of SOP.
从理论角度分析总结老年性骨质疏松症的发病原因,并通过实验研究探讨骨碎补总黄酮对骨髓基质细胞脂质化的影响,以及对成骨细胞衰变和凋亡的影响,从临床角度观察其治疗老年性骨质疏松症的效果,为临床应用提供科学理论依据。
方法:
临床研究:选择股骨近端BMD较同性别年轻成人均值低2.5SD以上,诊断为老年性骨质疏松症者70例。采用随机对照的方法,分为治疗组(口服强骨胶囊)36例,对照组(口服钙尔奇D)34例,依据对腰背痛及腰痛综合评分进行动态观察;依据“疼痛VAS线段分级法”对腰背痛(静止痛、翻身痛、久坐痛、起身痛、弯腰痛、步行痛、睡眠痛、叩击痛、压痛)进行量化动态观察;依据“Barthel指数评定法”对老年性骨质疏松症日常生活活动能力(ADL)进行观察;采用双能X线骨密度仪对腰椎(L_2-L_4)、股骨近端各部位:股骨颈(Neck)、股骨三角区(Ward)、股骨粗隆(Troch)进行骨密度(BMD)定量检测;应用放射免疫法对骨转换指标进行测定,骨形成指标:骨钙素(BGP)、Ⅰ型前胶原氨基端前肽(PINP);骨吸收指标:Ⅰ型胶原交联羧基末端肽(ICTP)等,评价骨碎补总黄酮治疗老年性骨质疏松症的临床效果。
实验研究:通过WST-8分析骨碎补总黄酮含药血清对大鼠骨髓基质细胞活性的影响;以地塞米松诱导骨髓基质细胞脂质化后,建立脂肪细胞与骨髓基质细胞的共培养体系,用骨碎补总黄酮含药血清干预后,以TUNEL法检测骨髓基质细胞的凋亡情况;采用三丁基过氧化氢(t-BHP)体外诱导大鼠成骨细胞衰老,用骨碎补总黄酮含药血清干预后,以SA-β-半乳糖苷酶(Se-nescence associatedβ-galactosidase)化学染色,观察细胞衰老情况;将大鼠成骨细胞培养于含有肿瘤坏死因子-α(TNF-α)或骨碎补总黄酮加TNF-α培养基中后,通过荧光染色细胞核DNA及电镜下超微结构观察,检测成骨细胞凋亡情况。
结果:
1.“疼痛六点行为评分法(BRS-6)”观察结果显示,治疗前老年性骨质疏松症患者的腰背痛及腰痛多在Ⅲ～Ⅴ级之间,疼痛无法忽视,对日常生活有一定的影响。运用强骨胶囊(骨碎补总黄酮)治疗3个月后疼痛分级多降至到Ⅰ～Ⅱ级,自觉疼痛基本消失。说明骨碎补总黄酮在一定程度上能够改善老年性骨质疏松症引起的腰背痛及腰痛,缓解疼痛的幅度以治疗的前3个月最为明显。
2.“疼痛VAS线段分级法”观察结果显示,治疗前静止时腰背痛、久坐时腰背痛、步行时腰背痛均呈现中度疼痛,翻身时腰背痛、起身时腰背痛、弯腰时腰背痛、腰背压痛与叩击痛多表现重度疼痛,而以弯腰时腰背痛、腰背叩击痛尤为显著,部分病人腰背痛对睡眠会有一定影响。运用骨碎补总黄酮治疗3个月后,各种行为方式引起的腰背痛均有不同程度的改善,其中治疗1个月后腰背痛对睡眠的影响较小,治疗2个月后多数静止痛、久坐痛基本消失,治疗3个月多数翻身痛、起身痛、步行痛、压痛可缓解,但部分病人仍然呈现出一定程度的弯腰痛和腰背叩击痛。由此可见,骨碎补总黄酮对老年性骨质疏松症病人静态生活方式出现的腰背痛改善迅速且明显,对动态生活方式引起腰背痛加重,以及外界干预加重的腰背痛也有一定的作用,但相对较慢。
3.“Barthel指数评定法”对日常生活活动能力(ADL)进行观察结果显示:治疗前多数病人Barthel指数评分为60～40分,表现中度残疾,有功能障碍,生活需要帮助;治疗3个月后积分可达到90分以上,生活基本自理,生活独立性有一定程度的改善,生活质量有很大提高。
4.双能X线骨密度仪对老年性骨质疏松症腰椎(L_2-L_4)、股骨近端各部位:股骨颈(Neck)、股骨三角区(Ward)、股骨粗隆(Troch)进行应用骨碎补总黄酮治疗前后骨密度(BMD)定量检测结果表明,应用骨碎补总黄酮治疗6个月后各部位BMD均有一定程度的升高;与对照组(钙尔奇D)相比,除外腰椎(L_2-L_4)的骨密度改善程度无差异,骨碎补总黄酮的治疗效果更为明显,二者对比,有显著性差异。说明骨碎补总黄酮对老年性骨质疏松症具有提高整体骨量的作用,同时能够提高股骨近端骨强度,预防髋部骨折。
5.骨代谢标志物检测结果表明,老年性骨质疏松症BGP、PINP比较正常成年人均有一定程度降低,说明老年性骨质疏松症成骨细胞功能衰退,合成胶原减少,成骨能力较弱;运用骨碎补总黄酮治疗6个月后,BGP、PINP均有一定程度上升,说明骨碎补总黄酮具有促进低转换型骨质疏松症骨胶原的合成,提高骨转换,增加骨形成等作用。老年性骨质疏松症ICTP比较正常成年人有一定程度升高,说明老年性骨质疏松症骨溶解增加,骨吸收相对较快。运用骨碎补总黄酮治疗6个月后,ICTP有一定程度上降低,说明骨碎补总黄酮具有减缓低转换型骨质疏松症骨吸收状况的功效。
6.骨碎补总黄酮含药血清对大鼠骨髓基质细胞活性的影响研究结果表明,经骨碎补总黄酮干预后大鼠骨髓基质细胞数量显著增加,说明骨碎补总黄酮能够提高大鼠骨髓基质细胞的活性,并具有促进其增殖分裂的作用。
7.骨碎补总黄酮对TNF-α诱导的大鼠成骨细胞凋亡的抑制作用研究结果表明,在用空白血清培养的成骨细胞中加入TNF-α,可见到成骨细胞出现凋亡征象,凋亡的成骨细胞显著增多;而用骨碎补总黄酮含药血清培养的成骨细胞,凋亡细胞明显减少,虽然仍有细胞凋亡的形态改变,但可部分对抗TNF-α所致的成骨细胞凋亡。
8.骨碎补总黄酮含药血清对脂质化大鼠骨髓基质细胞凋亡的保护作用研究结果表明,脂肪细胞能够诱导骨髓基质细胞的凋亡,用骨碎补总黄酮含药血清干预后,凋亡细胞明显减少,说明骨碎补总黄酮含药血清对脂质化大鼠骨髓基质细胞凋亡具有保护作用。
9.骨碎补总黄酮对大鼠成骨细胞衰老的影响研究表明,经t-BHP处理后的成骨细胞SA-β-半乳糖苷酶的细胞化学染色阳性的细胞数明显增多,而用骨碎补总黄酮干预的衰老细胞明显减少,说明骨碎补总黄酮含药血清对t-BHP诱导的大鼠成骨细胞衰老具有保护作用。
结论:
1.随着人类寿命的延长和人口老龄化,老年性骨质疏松症的发病率逐渐增加,严重危害着老年人的健康和生命。
2.老年性骨质疏松症是机体自然衰退、老化过程的组成部分,骨髓基质细胞分化方向改变和成骨细胞的生物学功能衰退是其发病的细胞病理学基础,而五脏虚损和气血功能紊乱与其发病密切相关,其中肾虚为其核心病机。
3.临床研究表明:骨碎补总黄酮具有促进老年性骨质疏松症骨胶原的合成,提高骨转换,增加骨形成,减缓骨吸收状况等作用,进而提高老年性骨质疏松的整体骨量,缓解腰背痛,提高股骨近端骨强度,预防髋部骨折,提升独立性生活水准,全面提高老年性骨质疏松症患者的生命质量。
4.实验研究表明:骨碎补总黄酮能够提高大鼠骨髓基质细胞的活性,促进其增殖分裂,并对脂质化大鼠骨髓基质细胞凋亡具有保护作用,而且骨碎补总黄酮含药血清对TNF-α诱导的大鼠成骨细胞凋亡和t-BHP诱导的大鼠成骨细胞衰老均具有一定的保护作用。实验研究结果说明,骨碎补总黄酮对增强老年性骨质疏松症成骨作用具有重要的意义。
Objective:
From the theoretical angle,to analyze and summarize the morbility reason of Senile Osteoporosis,to approach the effect of the flavone of rhizome drynaria on the lipidision of marrow stroma cell,as well as the senescence and apoptosis of osteoblast through the experimental study;from the clinical angle,to observe the clinical effect of the flavone of rhizome drynania on Senile Osteoporosis,to supply scientific theory basis for clinical application.
Methods:
Clinical study:70 patients with Senile Osteoporosis who were depended the diagnostic criteria,were divided into two groups randomly,36 patients in treat group (treated with the Qianggu capsule);34 patients in control group(treated with Caltrate D 600 chew tablet).Appraised the clinical effect of the flavone of rhizome drynania on Senile Osteoporosis,according to the dynamic observation on integrative scores of lumbodorsal pain and lumbodynia,"VAS section grading method" on lumbodynia, "Barthel index rating method" on ADL,detected BMD on anterior-posterior position lumbar2～4 vertebra body and proximate of femur including neck/ward/troch,and determined the index of bone transition including BGP/PINP/ICTP through the radioimmunity method before and after treated half a year,then contrast intragroup and selfgroup.Depending on the standard of curative effect,contrast the difference of curative effect between two groups.
experimental study:The effect of flavone of rhizome drynaria's serum in blood on cytoactive of marrow stroma cell of rats from analyse of WST-8.After dexamethasone induced lipidsion of marrow stroma cell,based the co-culture system of cell and marrow stroma cell.we use TUNEL standard detect the marrow stroma cells' apotosis,after intervened of flavone of rhizome drynaria's serum.Osteoblast senescence of rats by we uesd t-BHP induce in vitro,after we used the flavone of rhizome drynaria's serum intervene,Se-nescence associatedβ-galactosidase chemi-staining, observe the cell senescence.To detect the osteoblast apoptosis,after cultured rats' osteoblast in the medium including TNF-a or the the flavone of rhizome drynaria and TNF-a,by fluorescence staining DNA of nucleus,and observing ultrastructure under electron microscope.
Results:
1.The observation results of 6-points Behavioural Rating Scale(BRS-6) displayed,the lumbodosal pain and lumbodynia with pretherapy SOP patients nearly were three or four degree,ignored impossible.There is several impact to daily living.The lumbodosal pain and lumbodynia lowered to one or tow degree after 3 months treated by the flavone of rhizome drynaria,the aware pain vanished.To illustrate the flavone of rhizome drynaria can extently amend the lumbodosal pain and lumbodynia with SOP,the pain obviously released after 3 months.
2.The observation results of "VAS section grading method" displayed,the lumbodynia showed midrange pain while rest/prolonged sitting/walking,and heavy-range pain while to turn the body over/to get up/bend from the waist/tenderness/percussion pain before treated,is especial significance while /to turn the body over/ percussion pain.A piece of patients' lumbodynia impacted their sleep.Various kinds of lumbodynia amended diversity extently through the flavone of rhizome drynaria treated after 3 months.After 1 month,the effect of lumbodynia on sleep is extremely trifling;after 2 months,the majority of rest and prolonged sitting pains nearly vanished;after 3 months,the majority of pains while to turn the body over/to get up/bend from the waist/tenderness/percussion pain can amend,but a piece of patients still showed the pain that bend from the waist and the percussion pain.From that to illustrate the flavone of rhizome drynaria can quickly and obviously amend the lumbodynia that SOP patients showed in static life style,but amend slowly in dynamic life style and surrounding intervention.
3.The observation results of "Barthel index rating method" on ADL displayed,the majority of patients' scores were 60～40 before treated,their life with moderate disability and dysfunction need help.After 3 months,the scores can achieve above 90,life nearly self cared,living independence amended extently,quality of life improved quietly.
4.The results that detected BMD on anterior-posterior position lumbar2～4 vertebra body and proximate of femur including neck/ward/troch displayed,all positions' BMD improved extently through treated by the flavone of rhizome drynaria after 6 months.The treat group has more conspicuous therapeutic efficacy than control group,there is a significant difference between the two groups,except the BMD on anterior-posterior position lumbar2～4 vertebra body.To illustrate that the flavone of rhizome drynaria can improve proximate of femur bone strength,and prevent fracture of hip.
5.The results that determined bone metabolism maker displayed,the SOP patients' BGP and PINP lower than normal adults,to illustrate that the SOP patients' osteoblast function decayed,synthesis collagen decreased,and bone formation capability weaken.After 6 months treated,BGP and PINP all upgraded extently,to illustrate that the flavone of rhizome drynaria can promote collagen synthesis, improve bone transition,and increase bone formation.The SOP patients' ICTP more advanced than normal adults,to illustrate that the SOP patients' osteolysis increased and bone resorption was more quickly.After 6 months treated,the SOP patients' ICTP lowered extently,to illustrate that the flavone of rhizome drynaria can delay the bone resorption.
6.The study results that the effect of flavone rhizome drynaria's serum on cytoactive of marrow stroma cell of rats indicated,the marrow stroma cell's quantity significant increased after intervened of flavone of rhizome drynaria's serum in,to illustrate that the flavone of rhizome drynaria can improve the cytoactive of marrow stroma cell of rats and promote its multiplicative division.
7.The study results that the depressant action of flavone rhizome drynaria's serum to osteoblast apoptosis of rats induced by TNF-a indicated,osteoblast cultured in vacant serum adding TNF-a showed apoptotic signs,and the quantity of apoptotic osteoblast significant increased.Osteoblast cultured in flavone rhizome drynaria's serum that its apoptotic significant decreased,although has the chang of apoptotic morphous,also can partially antagnoise osteoblast apoptosis with TNF-a.
8.The study results that the protection of flavone rhizome drynaria's serum to apoptosis of lipidsion marrow stroma cell of rats indicated,adipocyte can induce apoptosis of marrow stroma cell,and it significant decreased after intervened of flavone of rhizome drynaria's serum,to illustrate that the flavone of rhizome drynaria can protect the apoptosis of lipidsion marrow stroma cell of rats.
9.The study results that the effect of flavone rhizome drynaria's serum on osteoblast senescence of rats indicated,quantity of osteoblast Se-nescence associatedβ-galactosidase which cytochmical staining positive increased obviously after induced by t-BHP,but the quantity of osteoblast senescence decreased obviously,after intervened of flavone of rhizome drynaria's serum,to illustrate that the flavone of rhizome drynaria can protect the osteoblast senescence of rats induced by t-BHP.
Conclusions:
1.The attack rate of SOP is gradually increasing with the mankind life extending and population aging,seriously jeopardizing the aged health and life.
2.SOP is ingredient of the organism natural retrogression and aging process.Its pathogenetic cell pathology is marrow stroma cells' different direction changing and osteoblastics' biological function decaying,as well as,is intimate correlated with five viscera consumptive disease and Qi-blood functional disorder,renal deficiency is the core pathogenesis of that.
3.Clinical study indicated:the flavone of rhizome drynaria can promote collagen synthesis,improve bone transition,increase bone formation,delay bone resorption, furthermore,improve SOP patients' integer bone mass and proximate of femur bone strength,and prevent fracture of hip.Eventually,the level of living independence amended and the quality of life improved overall.
4.Experimental study indicated:the flavone of rhizome drynaria can improve the cytoactive of marrow stroma cell of rats,promote its multiplicative division,and protect the marrow stroma cells' apotosis with lipidsion.The flavone of rhizome drynaria's serum can extently protect the osteoblast apoptosis of rats induced by TNF-a and the osteoblast senescence of rats induced by t-BHP.The results of empirical study to illustrate that the flavone of rhizome drynaria has considerable significance to improve the bone formation action of SOP.
引文
[1]刘忠厚,杨定焯,朱汉民,等.中国人骨质疏松症建议诊断标准[J].中国骨质疏松杂志,2000,6(1):1-3.
[2]王洪复,于明香.老年人成骨细胞形成功能的衰退与治疗[J].国外医学内分泌学分册,2003,23(2):79-80.
[3]王华松,陈庄洪,罗永湘.髓内脂肪细胞促骨髓基质细胞凋亡的实验研究[J].中国骨质疏松杂志,2005,11(3):325-328.
[4]Klein RF,Fausti KA,Carlos AS,et al.Ethanol inhibits human osteoblastic cell proliferation[J].Alcohol Clin ExpRes,1996,20(3):572-578.
[5]王洪复.老年骨质疏松细胞病理特点与治疗思考[J].老年医学与保健,2003,9(3):68-71.
[6]白云静,申洪波,张秋枫.原发性骨质疏松症从肾论治的理论探讨[J].中国矫形外科杂志,2002,9(6):619-620.
[7]谢雁鸣,赵晋宁,丁会,等.强骨胶囊抗去势大鼠骨质疏松症的实验研究[J].中国中医药科技,2000,7(3):151-152.
[8]盛彤,田金洲,胡玉宁,等.强骨胶囊治疗原发性骨量减少(肾阳虚证)的临床研究[J].中国医药学报,2002,17(7):413-415.
[9]王和鸣,田金洲,彭淑莲,等.强骨胶囊治疗骨质疏松早期骨量减少的临床观察[J].中国骨伤,2003,16(11):692-694.
[10]王林,汪建平.骨质疏松症的预防和治疗进展[J].西北药学杂志,2003,18(5):234-236.
[11]经济参考报,2004年10月22日
[12]薛延.骨质疏松症的流行病学概况[J].新医学,2007,38(1):7-8.
[13]迟家敏.老年人内分泌代谢系统疾病的流行病学研究[J].中华老年医学杂志,2003,22(6):326-327.
[14]栗庆山,梁道晨.原发性骨质疏松症的病因及治疗[J].现代康复,1999,3(5):612.
[15]刘忠厚,潘子昂,王石鹏,等.骨骼生长衰老规律和原发性骨质疏松症预诊的研究[J].中国骨质疏松杂志,1995,1(1):1.
[16]Davidson M,DeSimone E.Osteoporosis update[J].Clin Rev,2002,12(4):75-82.
[17]黄公怡.骨质疏松性骨折的诊断和治疗[J].国际内分泌代谢杂志,2006,26(4):233-234.
[18]Hajcsar EE,Hawker G,Bogoch ER et al.Investigation and treatment of osteoporosis in patients with fragility fractures[J].CMAJ,2000,163(7):819-822
[19]崔彦红节译.骨质疏松防治展望[J].国外医学·卫生学分册,1999,22(1):32.
[20]Lane JM,Riley,Wirganowiez.Osteoporosis:diagnosis and treatment[J].J Bone Joint Surg Am,1996,78:618.
[21]朱建民.骨质疏松症的发病原因及防治[J].中华内科杂志,1999,11(31):714.
[22]杨定焯.骨质疏松与骨折[J]。实用妇产科学杂志,1999:11(5):232
[23]Stavros CM.Birth and death of bone cells:basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis[J]. Endocrine Reviews, 2000,21(2):115-137.
[24]Parfitt AM, Han ZH, Palnitkar S, et al. Effects of ethnicity and age or menopause on osteoblast function, bone mineralization, and osteoid accumulation in iliac bone[J].J Bone Miner Res,1997,12:1864-1873.
[25]Jilka RL, Weinstein RS, Takahashi K, et al. Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence[J]. J Clin Invest, 1996, 97(7):1732-1740.
[26]D' ippolito G, Schiller PC, Ricordi C, et al. Age-realated osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow[J]. J Bone Miner Res, 1999,14(7): 1115-1122.
[27]Lecka-Czernik B, Gubrij I, Moerman E, et al. Inhibition of 0sf2/cbfal expression and terminal osteoblast differentiation by PPARy2[J].J Cell Biochera, 1999, 74:357-371.
[28]Frost HM. Defining osteopenias and osteoporosis: another view (with insight form a new paradigm)[J].Bone,1997,20:385-391.
[29]John PB. Osteoporosis in men[J].The Journal of Clinical Endocrinology & Metabolism, 1999,84(10):3431-3434.
[30]Uitterlinder AG, Burger H, Huang Q. Relation of alleles of the collagen type I alpha I gene to bone density and the risk of osteoporotic fractures in postmenopausal woman[J].N Engl J Med, 1998, 338:1016-1021.
[31]Langdahl BL, Lokke E, Carstens M, et al. Polymorphisms in the estrogen receptor gene show different distribution in osteoporotic patients and normal controls [J]. J Bone Miner Res, 1997,12(Suppl1):F581.
[32]Marie P. Growth factors and bone formation in osteoporosis: roles for IGF-I and TGF-β [J].Rev Rhum Engl Ed, 1997,64(1):44-53.
[33]Langdahl BL, Knudsen JY, Jensen HK, et al. A sequence variation:713-8delc in the transforming growth factor-betalgene has higher prevalence in osteoporotic women then in normal women and is associated with very low bone mass in osteoporotic women and increased bone turnover in both osteoporotic and normal women[J]. Bone, 1997, 20:289-294.
[34]Rosen CJ, Kurland ES, Vereault D, et al. Association between serum IGF-1and a simple sequence repeat in the IGF-1 gene: implications for genetic studies of bone mineral density[J]. J Clin Endocrinol Metab, 1998, 83:2286-2290.
[35]Morrison NA, Qi JC, Tokita A, et al. Prediction of bone density from vitamin D receptor alleles[J]. Nature, 1994, 367:284-287.
[36]Tsai KS, Hsu SHJ, Cheng WC, et al. Bone mineral density and bone markers in relation to vitamin D receptor gene polymorphisms in Chinese men and women[J].Bone,1996,19:513-518.
[37]Takeda N,Tsuboyama T,Kasac R,et al.Expression of the c-los gene induced by parathyroid hormone in the bones of SAMP6 mice,a murine model for senile osteoporosis[J].Mech Ageing Dev,1999,108(1):87-97.
[38]黄洪,田成功.睾酮与雄性大鼠骨质疏松关系的实验研究[J].中华内分泌杂志,1999,15(11):304-7.
[39]Anderson FH,Francis RM,Selby PL,et al.Sex hormones and osteoporosis in men [J].Calcified Tissue International,1998,62:185-188.
[40]戴居云.骨质疏松症的中西医治疗[M].上海:上海中医药大学出版社,2002.14-20.
[41]田军,陶天遵,王凯夫,等.老年男性骨质疏松及雌激素受体的研究进展[J].中国骨质疏松杂志,2005,11(1):95-98.
[42]刘汴生,张思雄.实用临床老年病学[M].北京:中国医药科技出版社,2001.553-555.
[43]S.H.Schanla,R.Ziegler.维生素D及其代谢产物在骨质疏松症发病机制与治疗中的意义[J].德国医学,1995,12(3)157-158.
[44]李珂欣,闻成艳,兰丹.老年人骨质疏松症的病因及防治[J].中国临床康复,2002,6(7):1058-1059.
[45]Duppe H,Gardsell P,HansonBS,et al.Bone mineral density in female junior,senior and former football players[J].Osteoporos Int,1996,6(6):437.
[46]秦林林,陈金标,马海波,等.不同运动水平对15～50岁正常人骨密度(BMD)影响的研究[J].中国骨质疏松杂志,1999,5(3):17.
[47]方圻,朱元珏,史轶繁,等.现代内科学[M].北京:人民军医出版社,1995.2779-2781.
[48]刘忠厚.骨质疏松学[M].北京:科学出版社,1998.202-208.
[49]曹建中.老年骨内科与骨疾病[M].北京:中国医药科技出版社,1994.68-72.
[50]CauleyJA.Osteoporosis:a worldwide disease[J].Medicograpgy,2004,26:215-220.
[51]郭洪敏,杜靖远..细胞凋亡与骨质疏松[J].国外医学老年医学分册,1999,20:49-52.
[52]郑强,范清宇.雌激素与绝经后骨质疏松[J].国外医学老年医学分册,1998,19:132-135.
[53]刘汴生,张思雄.实用临床老年病学[M].北京:中国医药科技出版社,2001.553-555.
[54]喻永新,冯新送,刘庆思,等.骨质疏松的防治研究近况[J].中国中医骨伤科杂志,2001,9(2):60-63.
[55]李卫平,张艳,明亮,等.糖皮质激素诱导大鼠骨质疏松模型及依扑拉芬对其作用的影响[J].中国药理学通报,1999,15:474-476.
[56]Osteoporosis.November 2000:Updated following publication of theupdate to the Royal College of Physicians guideline on osteoporosis,2000.
[57]李明,熊方武.骨质疏松症治疗药物:雷洛昔芬[J].国外医学-合成药生物药制剂册,1999,20:87-88.
[58]Clemett D,Spencer CM.Raloxifene:a review of its use inpostmenopausal osteoporosis[J].Drugs,2000,60:379-411.
[59]Hognauer D,Welch V,SheaB,et al.Fluoride for treating postmenopausal osteoporosis[J].The Cochrane Library,Issue 2,Oxford:Update software,2001.
[60]Liu GP,Kang B,Zeng H.Study of the curative ffect of alendronate in osteoporosis of middle age and senile patients[J].J Am Chin Traum,2001,3:7.
[61]薛延.骨质疏松症诊断与治疗指南[M].北京:科学出版社,1999:60.
[62]杨广忠.老年骨质疏松性股骨粗隆间骨折的疗效分析[J].中国骨质疏松杂志,2007,13(4):274-276
[63]丁桂芝,李榕.从骨矿含量变化规律看肾主骨理论的科学性[J].湖北中医杂志,1991,13(2):27
[64]赵玉堂,刘凯军,李金花,等.骨矿含量与肾虚、肾主骨关系的研究[J].中国骨质疏松杂志,1996,2(3):19.
[65]李巧如,候冬梅,刘勤社.试论肾主骨生髓的科学性[J].陕西中医,1999,20(3):143.
[66]崔若兰.现代肾脏病药物治疗学[M].北京:人民军医出版社,2001,183-214.
[67]Pedersen I,Kremer M,Judd J et al.Androgens regulate bone resorption activity of isolated osteoclsts in vitro[J].Proe Natl Acad Sci U S A 1999,96(2):505-10.
[68]郭世绂.骨质疏松基础与临床[M].天津:天津科技出版社.2001.535.
[69]侯淑琴,肖占森.绝经妇女骨代谢变化及雌激素对骨代谢的影响[J].中国骨质疏松杂志,2000,6(1):72 73.
[70]张俐,王占朝,张安桢,等.男性原发性骨质疏松症中医证型的实质探讨[J].中国中医骨伤科杂志,2004,12(3):1.
[71]金世鑫.男性骨质疏松症诊断和治疗[J].中国骨质疏松杂志,2000,6(3):72-75.
[72]邸明芝,庞炜,王治伦.部分细胞因子在原发性骨质疏松症发病机理中的作用[J].中国骨质疏松杂志,2000,6(2):87-90.
[73]赵燕玲,丁桂芝,刘忠厚,等.原发性骨质疏松症的发病机理[J].中国骨质疏松杂志,1998,4(4)73-77.
[74]The development of the WHO quality of life assessment instrument[S].Geneva,WHO,1993:1.
[75]Badia X,Prieto I,Roset M,et al development of the ECOS-16clinical questionnaine for the assessment of the quality of life in patients with osteoporosis[J].Med Clin,2000,114(Suppl 3):68-75.
[76]黄如娇,韦坚,黄美蔼,等.骨质疏松症患者的生活质量研究及护理干预影响[J].中国全科医学,2006,(11):1798-1800.
[77]Deborah J.Cook,Gordon H,et al.Quality of life issues in women with vertebral fractures due to osteoporosis[J].Arthritis and Rheumatism,1993,36(6):750.
[78]黄如娇,韦坚,黄美蔼,等.骨质疏松症患者的生活质量研究及护理干预影响[J].中国全科医学,2006,(11):1798-1800.
[79]Jarvinen M,Kannus P.Injury of an extremity as a risk factor for the development of osteoporosis[J].J Bone Jonit Surg,1997,79A,263-276.
[80]陈金标,秦林林.骨质疏松症与遗传[J].中国骨质疏松杂志,2000,6(2):89-91.
[81]王洪复.骨质疏松症的诊断[J].国际内分泌代谢杂志,2006,26(4):285-288.
[82]Lane JM,Riley EH,Wirganowicz PZ.Osteoporosis:Diagnosis and Treatment[J].J Bone Joint Surg,1996,78A:618.
[83]ChisholmMA,Mulloy A1.Management of osteoporosis in the elderly[J].J Geriatric Drug Therapy,1996,11(1):5-15.
[84]李险峰.骨质疏松症的临床表现、检查及诊断[J].新医学,2007,38(1):18-11.
[85]李景学.骨矿物质影像学研究的新趋向[J].中华放射学杂志,1996,30:56-58.
[86]张兴雨,秦沛.腰椎和髋部骨密度测定在骨质疏松诊断上的相关性分析[J].中国临床康复,2005,9(3):198-199.
[87]Liu B,Wang C,Yang M,et al.Clinical value of urinary deoxypyridionllne excretion in postmenopausal osteoporosis[J].Chinese Journal Osteoporosis,2002,8:43-46(in Chinese).
[88]Xiao Y,Zhang J,Hua B,e tal.Experimental Study of QCT in predicting the Strength of Vertebra[J].Chinese Journal of Medical Imaging Technology,2002,18:625-627(in Chinese).
[89]Zhang J,Deng J,Ouyang Q,et al.Acomparative study of bone mineral density and bone metabolic markers in primary osteoporosis[J].Chinese Journal of Osteoporosis,2OOS,11:319-324(in Chinese).
[90]King X,Ren A,Yang J,et al.Application of procollagen IN-Termina extension peptides in the diagonosis of Osteoporosis[J].Acta Universitatis Medicinalis Anhui,1999,34(5):361-363.
[91]Garnero P,Ferreras M,Karsdal MA,et al.Thetype Ⅰ collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation[J].J Bone Miner Res,2003,18:859-867.
[92]Charles P,Mosekilde L,RisteliL,et al.Assessment of bone remodeling using biochemical indicators of type I collagen synthesis and degredation:relation to calcium kinetics[J].Bone Miner,1994,24:81-94.
[93]Zhang J,Deng J,Ouyang Q,et al.Acomparative study of bone mineral density and bone metabolic markers in primary osteoporosis[J].Chinese Journal of Osteoporosis,2OO5,11:319-324(in Chinese).
[94]许士凯,陈再智.老年生理学与病理学研究进展(之一)[J].现代中西医结合杂志2005,14(2):146-148
[95]王洪复,于名香.老年人成骨细胞形成功能的衰退与治疗[J].国外医学内分泌学分册2003,23(2):79-81.
[96]Parfitt AM.The mechanism of coupling:a role for the vasculature[J].Bone,2000,26:319.
[97]王维,何成奇.骨质疏松症与衰老的关系[J].中国临床康复,2005,9(7):93-95.
[98]Wyllie AH,Kerr JER,Currie AR et al.Celld eath:thesig-nificance of apoptosis[J]IntRevCytol,1980,68(1):25-307.
[99]KleinRF,Fausti KA,Carlos AS,et al.Ethanol inhibits human osteoblastic cell proliferation[J].Alcohol Clin ExpRes,1996,20(3):572-578.
[100]Ookawa K,Tisuchida S,Adachi J,et al.Differentiation inducedby RB expression and apoptosis induced by p53 expression in an osteosarcoma cell line[J].Oncogene,1997,14(12):1389-1396.
[101]Kawakami A,Nakane PK,Matsuka N,et al.Fas and Faslig and interaction is necessary for human osteoblast apoptosis[J].J Bone Mine rRes,1997,12(10):1637-1646.
[102]Hil 1PA,Tumber A,Meikle MC,et al.Multiple extracellular signal spromote osteoblast survival and apoptosis[5].Endocrinology,1997,138(9):3849-3858.
[103]Jilka RL,Weinstein T,Bellido AM,et al.Osteoblast programmed cell death:modulation by growth factors and cytokines[J].J Bone Miner Res,1998,13(3):793-802.
[104]Robert S,Weistein RL,Michae P,et al.Inhibition of osteoblastogenesis and Promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids[J].J ClinInvest,1998,102(2):274-282.
[105]Pittenger MF,Mackay AM,Beck SC et al.Multilineage potential of adult human mesenchymal stem cells[J].Science,1999,284:143-147.
[106]王和鸣,王力.巴戟天对骨髓基质细胞向成骨细胞方向分化影响的实验研究.福建中医学院院报,2004,14(3):16.
[107]郑良朴,李椭,王和鸣.补骨合剂对体外培养骨髓基质细胞分化影响的观察[J].福建中医学院学报,2003,13(6):33.
[108]徐展望,张建新,李军等.骨碎补提取液对兔骨髓基质细胞增殖的影响[J].中医正骨,2005,17(4):1-3.
[109]邓展生,张璇,邹冬青,等.骨碎补各种提取成分对人骨髓间充质干细胞的影响[J].中国现代医学杂志,2005,15(16):2426-2429.
[110]王华松,陈庄洪,罗永湘.髓内脂肪细胞促骨髓基质细胞凋亡的实验研究[J].中国骨质疏松杂志,2005,11(3):325-328.
[111]张兴凯,杨庆铭,邓廉大,等.骨质疏松症成骨细胞生物学特征的体外研究[J].中国骨质琉松杂志,2004,10(1):48-50.
[112]Mazess RB.Fracture risk:a role for compact bone[J].Calcif Tissue Int,1990,47:191-193.
[1]Eriksen EF,Langdahl BL.The pathogensis of osteoporosis[J].Horm one Research,1997,48(Supple.5):78-82.
[2]张兴凯,杨庆铭,邓廉夫等.骨质疏松症成骨细胞生物学特征的体外研究[J].中国骨质疏松杂志,2004,10(1):48-50.
[3]MazessRB.Fracture risk:a role for compact bone[J].Calcif Tissue Int,1990,47:191-193.
[4]Weinstein RS,Jilka RL,Parfitt AM,etal.Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids:potential mechanisms of their deleterious effect on bone[J].J Clin Invest,1998,102:274-282.
[5]李靖,王全平.细胞凋亡与骨质疏松关系的研究进展[J]中华骨科杂志,2001,21(5):305-307.
[6]沈霖,杜靖远,周丕琪等.补肾法对TNF-a诱导新生大鼠成骨细胞凋亡的保护作用[J].中国中医骨伤科杂志,2000,8(1)2-4.
[7]韩清民,施佳平,林一峰等.肿瘤坏死因子α诱导大鼠成骨细胞凋亡与中药骨康的干预效应[J].中国临床康复,2005,9(23):170-172.
[8]王玉东,李大金,朱影等.补肾宁心方对小鼠成骨细胞的增殖和抗凋亡作用[J].中国中西医结合杂志,2004,24(3):230-233.
[9]李楠,王和鸣,林旭等.补骨合剂对全反式维甲酸诱导的骨髓基质细胞凋亡的保护作用[J]中西医结合学报2002(5):367-371.
[10]高晓燕,孟艳彬,赵春颖.补肾中约对成骨样细胞UMRl06增殖的影响[J].承德医学院学报,2002,19(1):7-9.
[11]李娟,吴伟康,余克强.不同实验浓度补肾中药血清对人成骨细胞增殖及分化的促进作用[J].中国临床康复,2005,9(19):82-84.
[12]曲耀华,刘彬,厉永强.补肾方剂对大鼠成骨样细胞增殖及相关酶类的影响[J].山东中医杂志,2003,22(7):424-425.
[13]lian JB,Gunderg CM,Osteocalcin.Biochemical consideration and clinical applications[J].Clin Orthop Rel Res,1987,226(2):267-270.
[14]邢国胜,谈志龙,王淑云等.补肾健骨汤对成骨细胞增殖及碱性磷酸酶、骨钙素合成的影响[J].中草药,2001,32(11):1020-1022.
[15]李冬华,朱飞鹏.补肾中药对体外培养成骨细胞增殖和功能的影响[J].中药药理与临床,2005,21(2):32-34.
[16]王俊勤,胡有谷,郑洪军等.淫羊藿甙对体外培养成骨细胞增殖和分化的影响[J].中国临床康复,2002,6(9):1307-1308.
[17]Bellows CG,Aubin JEM,Rntosa ME.Mineralized bone nodules formed in vitro from enzymatically released rat calvaria populations[J].Calcif Tissue Jnt,1986,38:143
[18]唐井钢,李娟,吴贺勇.喂饲补肾中药大鼠的血清对成骨细胞的生物学作用[J].第一军医大学学报,2004,24(11):1248-1250.
[19]李娟,吴伟康,孙炜等.补肾中药对人成骨细胞钙离子摄取和钙化能力的影响[J].第一军医大学学报,2004,24(12):1359-1361.
[20]马金,姜涌,郑洪新,密骨颗粒含药血清对大鼠成骨样细胞增殖及Ca~(2+)/CaM信使1005-1007系统影响的研究[J].中医药学刊,2004,22(6):1005-1007.
[21]Erlebacher A,Derrnck R.Increased expression of TGF-beta in osteoblast results anosteoporosis like phenotype[J].Journal of Cell Biology 1996,132:192-199.
[22]邸明芝,庞炜,王治伦.部分细胞因子在原发性骨质疏松症发病机理中的作用[J].中国骨质疏松杂志,2000,6(2):87-90.
[23]沈霖,杜靖远,曾晖等.补肾方对成骨细胞生长因子TGF-β 1mRNA表达的影响[J].中医正骨,2001,13(5):3-5.
[24]任艳玲,郑洪新,杜松.补肾健脾药物血清对大鼠成骨细胞TGF-β1表达的影响[J].辽宁中医杂志,2005,32(2):100-102.
[25]Heldin CH,MiyazonoK,ten Dijke P.TGF-β signaling from cell membrarn to nucleus through SMAD proteins[J].Nature,1997,390:465-471.
[26]任艳玲,郑洪新,杜松.补肾健脾药物血清对大鼠成骨细胞Smad2 mRNA表达影响的研究[J].中医药学刊,2005,23(4):618-620.
[27]雪原,王沛,齐清会等.淫羊藿甙对成骨细胞Smad4 mRNA作用的实验研究[J].中华骨科杂志,2005,25(2):119-123.
[28]任艳玲,郑洪新,杜松.补肾健脾药物血清对人鼠成骨细胞信号转导分子Smad4表达的影响[J.]中国老年学杂志,2005,25(3):289-291.
[1]王和鸣,葛继荣,田金洲,等.强骨胶囊治疗原发性骨质疏松症临床试验[J].中药新药与临床药理,2004,15(4):284-287.
[2]刘剑刚,谢雁鸣,赵晋宁,等.骨碎补总黄酮胶囊对实验性骨质疏松症和镇痛作用的影响[J].中国实验方剂学杂志,2004,10(5):31-34.
[3]谢雁鸣,许勇钢,赵晋宁,等.骨碎补总黄酮对去卵巢大鼠骨密度和细胞因子IL-6、IL-4、TNF α水平的影响[J].中国中医基础医学杂志,2004,10(1):34-37.
[4]马克昌,高子范,冯坤,等.骨碎补提取液对小鸡骨发育的促进作用[J].中医正骨,1990,2(4):7.
[5]马克昌,朱太咏,刘鲜姑,等.骨碎补注射液对培养中鸡胚骨原基钙化的促进作用[J].中国中药杂志,1995,20(3):178.
[6]谢雁鸣,赵晋宁,张文军强等.骨胶囊抗维甲酸所致大鼠骨质疏松症的实验研究[J].中药新药与临床药理,1998,9(4):217-220.
[7]谢雁鸣,赵晋宁,丁会,等.强骨胶囊抗去势大鼠骨质疏松症的实验研究[J].中国中医药科技,2000,7(3):151-152.
[8]Kalu DN,Liu CC,Hardin RR et al.The aged rat model of ovarian hormone deficiency bone loss[J].Endocrinology,1989,124(1):7.
[9]谢雁鸣,鞠大宏,赵晋宁.骨碎补总黄酮对去卵巢大鼠骨密度和骨组织形态计量学影响[J].中国中药杂志,2004,29(4):343-346
[10]马中书,王蕊,邱明才,等.四种补肾中药对去卵巢大鼠骨质疏松骨形态的作用[J].中华妇产科杂志,1999,34(2):82-85。
[11]张兴凯,杨庆铭,邓廉夫,等.骨质疏松症成骨细胞生物学特征的体外研究[J].中国骨质疏松杂志,2004,10(1):48-50.
[12]Mazess RB.Fracture risk:a role for compact bone[J].Calcif Tissue Int,1990,47:191-193
[13]谢雁鸣,秦林林,邓文龙,等.骨碎补总黄酮对成骨细胞体外培养作用的机制研究[J].中华中医药杂志,2005,20(3):161-162.
[14]唐琪,陈莉丽,严杰.骨碎补提取物促小鼠成骨细胞株MC3T3-E1细胞增殖、分化和钙化作用的研究[J].中国中药杂志,2004,29(2):164-168.
[15]Pittenger MF,Mackay AM,Beck SC et al.Multilineage potential of adult human mesenchymal stem cells[J].Science,1999,284:143-147.
[16]王和鸣,王力.巴戟天对骨髓基质细胞向成骨细胞方向分化影响的实验研究[J].福建中医学院院报,2004,14(3):16.
[17]郑良朴,李椭,王和鸣.补骨合剂对体外培养骨髓基质细胞分化影响的观察[J].福建中医学院学报,2003,13(6):33
[18]徐展望,张建新,李军等.骨碎补提取液对兔骨髓基质细胞增殖的影响[J].中医正骨,2005,17(4):1-3.
[19]邓展生,张璇,邹冬青,等.骨碎补各种提取成分对人骨髓间充质干细胞的影响[J].中国现代医学杂志,2005,15(16):2426-2429.
[20]Eriksen EF,Langdahl BL.The pathogensis of osteoporosis[J].Horm one Research,1997,48(Supple.5):78-82.
[21]樊粤光,黄永明,曾意荣,等.骨碎补提取液对体外分离破骨细胞性骨吸收的作用[J].中国中医骨伤科杂志,2003,11(6):4-6.
[22]刘金文,黄永明,许少健,等.中药骨碎补对大鼠骨髓破骨细胞体外培养的影响[J].中医研究,2005,18(7):5-7.
[23]邸明芝,庞炜,王治伦.部分细胞因子在原发性骨质疏松症发病机理中的作用[J].中国骨质疏松杂志,2000,6(2):87-90.
[24]谢雁鸣,许勇钢,赵晋宁,等.骨碎补总黄酮对去卵巢大鼠骨密度和细胞因子.IL-6、IL-4、 TNFα水平的影响[J].中国中医基础医学杂志,2004,10(1):34-37.
[25]Erlebacher A,Derrnck R.Increased expression of TGF-beta in osteoblast results anosteoporosis like phenotype[J].Journal of Cell Biology 1996,132:192-199.
[26]王华松,许申明.骨碎补对骨折愈合中TGF-β1表达的影响[J].中国中医骨伤科杂志,2001,9(4):10-13.
[27]谢雁鸣,张露,王智,等.骨碎补总黄酮对去卵巢大鼠基因水平的影响[J].中国中药杂志,2005,30(14):1092-1095.
[2]王洪复,于明香.老年人成骨细胞形成功能的衰退与治疗[J].国外医学内分泌学分册,2003,23(2):79-80.
[3]王华松,陈庄洪,罗永湘.髓内脂肪细胞促骨髓基质细胞凋亡的实验研究[J].中国骨质疏松杂志,2005,11(3):325-328.
[4]Klein RF,Fausti KA,Carlos AS,et al.Ethanol inhibits human osteoblastic cell proliferation[J].Alcohol Clin ExpRes,1996,20(3):572-578.
[5]王洪复.老年骨质疏松细胞病理特点与治疗思考[J].老年医学与保健,2003,9(3):68-71.
[6]白云静,申洪波,张秋枫.原发性骨质疏松症从肾论治的理论探讨[J].中国矫形外科杂志,2002,9(6):619-620.
[7]谢雁鸣,赵晋宁,丁会,等.强骨胶囊抗去势大鼠骨质疏松症的实验研究[J].中国中医药科技,2000,7(3):151-152.
[8]盛彤,田金洲,胡玉宁,等.强骨胶囊治疗原发性骨量减少(肾阳虚证)的临床研究[J].中国医药学报,2002,17(7):413-415.
[9]王和鸣,田金洲,彭淑莲,等.强骨胶囊治疗骨质疏松早期骨量减少的临床观察[J].中国骨伤,2003,16(11):692-694.
[10]王林,汪建平.骨质疏松症的预防和治疗进展[J].西北药学杂志,2003,18(5):234-236.
[11]经济参考报,2004年10月22日
[12]薛延.骨质疏松症的流行病学概况[J].新医学,2007,38(1):7-8.
[13]迟家敏.老年人内分泌代谢系统疾病的流行病学研究[J].中华老年医学杂志,2003,22(6):326-327.
[14]栗庆山,梁道晨.原发性骨质疏松症的病因及治疗[J].现代康复,1999,3(5):612.
[15]刘忠厚,潘子昂,王石鹏,等.骨骼生长衰老规律和原发性骨质疏松症预诊的研究[J].中国骨质疏松杂志,1995,1(1):1.
[16]Davidson M,DeSimone E.Osteoporosis update[J].Clin Rev,2002,12(4):75-82.
[17]黄公怡.骨质疏松性骨折的诊断和治疗[J].国际内分泌代谢杂志,2006,26(4):233-234.
[18]Hajcsar EE,Hawker G,Bogoch ER et al.Investigation and treatment of osteoporosis in patients with fragility fractures[J].CMAJ,2000,163(7):819-822
[19]崔彦红节译.骨质疏松防治展望[J].国外医学·卫生学分册,1999,22(1):32.
[20]Lane JM,Riley,Wirganowiez.Osteoporosis:diagnosis and treatment[J].J Bone Joint Surg Am,1996,78:618.
[21]朱建民.骨质疏松症的发病原因及防治[J].中华内科杂志,1999,11(31):714.
[22]杨定焯.骨质疏松与骨折[J]。实用妇产科学杂志,1999:11(5):232
[23]Stavros CM.Birth and death of bone cells:basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis[J]. Endocrine Reviews, 2000,21(2):115-137.
[24]Parfitt AM, Han ZH, Palnitkar S, et al. Effects of ethnicity and age or menopause on osteoblast function, bone mineralization, and osteoid accumulation in iliac bone[J].J Bone Miner Res,1997,12:1864-1873.
[25]Jilka RL, Weinstein RS, Takahashi K, et al. Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence[J]. J Clin Invest, 1996, 97(7):1732-1740.
[26]D' ippolito G, Schiller PC, Ricordi C, et al. Age-realated osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow[J]. J Bone Miner Res, 1999,14(7): 1115-1122.
[27]Lecka-Czernik B, Gubrij I, Moerman E, et al. Inhibition of 0sf2/cbfal expression and terminal osteoblast differentiation by PPARy2[J].J Cell Biochera, 1999, 74:357-371.
[28]Frost HM. Defining osteopenias and osteoporosis: another view (with insight form a new paradigm)[J].Bone,1997,20:385-391.
[29]John PB. Osteoporosis in men[J].The Journal of Clinical Endocrinology & Metabolism, 1999,84(10):3431-3434.
[30]Uitterlinder AG, Burger H, Huang Q. Relation of alleles of the collagen type I alpha I gene to bone density and the risk of osteoporotic fractures in postmenopausal woman[J].N Engl J Med, 1998, 338:1016-1021.
[31]Langdahl BL, Lokke E, Carstens M, et al. Polymorphisms in the estrogen receptor gene show different distribution in osteoporotic patients and normal controls [J]. J Bone Miner Res, 1997,12(Suppl1):F581.
[32]Marie P. Growth factors and bone formation in osteoporosis: roles for IGF-I and TGF-β [J].Rev Rhum Engl Ed, 1997,64(1):44-53.
[33]Langdahl BL, Knudsen JY, Jensen HK, et al. A sequence variation:713-8delc in the transforming growth factor-betalgene has higher prevalence in osteoporotic women then in normal women and is associated with very low bone mass in osteoporotic women and increased bone turnover in both osteoporotic and normal women[J]. Bone, 1997, 20:289-294.
[34]Rosen CJ, Kurland ES, Vereault D, et al. Association between serum IGF-1and a simple sequence repeat in the IGF-1 gene: implications for genetic studies of bone mineral density[J]. J Clin Endocrinol Metab, 1998, 83:2286-2290.
[35]Morrison NA, Qi JC, Tokita A, et al. Prediction of bone density from vitamin D receptor alleles[J]. Nature, 1994, 367:284-287.
[36]Tsai KS, Hsu SHJ, Cheng WC, et al. Bone mineral density and bone markers in relation to vitamin D receptor gene polymorphisms in Chinese men and women[J].Bone,1996,19:513-518.
[37]Takeda N,Tsuboyama T,Kasac R,et al.Expression of the c-los gene induced by parathyroid hormone in the bones of SAMP6 mice,a murine model for senile osteoporosis[J].Mech Ageing Dev,1999,108(1):87-97.
[38]黄洪,田成功.睾酮与雄性大鼠骨质疏松关系的实验研究[J].中华内分泌杂志,1999,15(11):304-7.
[39]Anderson FH,Francis RM,Selby PL,et al.Sex hormones and osteoporosis in men [J].Calcified Tissue International,1998,62:185-188.
[40]戴居云.骨质疏松症的中西医治疗[M].上海:上海中医药大学出版社,2002.14-20.
[41]田军,陶天遵,王凯夫,等.老年男性骨质疏松及雌激素受体的研究进展[J].中国骨质疏松杂志,2005,11(1):95-98.
[42]刘汴生,张思雄.实用临床老年病学[M].北京:中国医药科技出版社,2001.553-555.
[43]S.H.Schanla,R.Ziegler.维生素D及其代谢产物在骨质疏松症发病机制与治疗中的意义[J].德国医学,1995,12(3)157-158.
[44]李珂欣,闻成艳,兰丹.老年人骨质疏松症的病因及防治[J].中国临床康复,2002,6(7):1058-1059.
[45]Duppe H,Gardsell P,HansonBS,et al.Bone mineral density in female junior,senior and former football players[J].Osteoporos Int,1996,6(6):437.
[46]秦林林,陈金标,马海波,等.不同运动水平对15～50岁正常人骨密度(BMD)影响的研究[J].中国骨质疏松杂志,1999,5(3):17.
[47]方圻,朱元珏,史轶繁,等.现代内科学[M].北京:人民军医出版社,1995.2779-2781.
[48]刘忠厚.骨质疏松学[M].北京:科学出版社,1998.202-208.
[49]曹建中.老年骨内科与骨疾病[M].北京:中国医药科技出版社,1994.68-72.
[50]CauleyJA.Osteoporosis:a worldwide disease[J].Medicograpgy,2004,26:215-220.
[51]郭洪敏,杜靖远..细胞凋亡与骨质疏松[J].国外医学老年医学分册,1999,20:49-52.
[52]郑强,范清宇.雌激素与绝经后骨质疏松[J].国外医学老年医学分册,1998,19:132-135.
[53]刘汴生,张思雄.实用临床老年病学[M].北京:中国医药科技出版社,2001.553-555.
[54]喻永新,冯新送,刘庆思,等.骨质疏松的防治研究近况[J].中国中医骨伤科杂志,2001,9(2):60-63.
[55]李卫平,张艳,明亮,等.糖皮质激素诱导大鼠骨质疏松模型及依扑拉芬对其作用的影响[J].中国药理学通报,1999,15:474-476.
[56]Osteoporosis.November 2000:Updated following publication of theupdate to the Royal College of Physicians guideline on osteoporosis,2000.
[57]李明,熊方武.骨质疏松症治疗药物:雷洛昔芬[J].国外医学-合成药生物药制剂册,1999,20:87-88.
[58]Clemett D,Spencer CM.Raloxifene:a review of its use inpostmenopausal osteoporosis[J].Drugs,2000,60:379-411.
[59]Hognauer D,Welch V,SheaB,et al.Fluoride for treating postmenopausal osteoporosis[J].The Cochrane Library,Issue 2,Oxford:Update software,2001.
[60]Liu GP,Kang B,Zeng H.Study of the curative ffect of alendronate in osteoporosis of middle age and senile patients[J].J Am Chin Traum,2001,3:7.
[61]薛延.骨质疏松症诊断与治疗指南[M].北京:科学出版社,1999:60.
[62]杨广忠.老年骨质疏松性股骨粗隆间骨折的疗效分析[J].中国骨质疏松杂志,2007,13(4):274-276
[63]丁桂芝,李榕.从骨矿含量变化规律看肾主骨理论的科学性[J].湖北中医杂志,1991,13(2):27
[64]赵玉堂,刘凯军,李金花,等.骨矿含量与肾虚、肾主骨关系的研究[J].中国骨质疏松杂志,1996,2(3):19.
[65]李巧如,候冬梅,刘勤社.试论肾主骨生髓的科学性[J].陕西中医,1999,20(3):143.
[66]崔若兰.现代肾脏病药物治疗学[M].北京:人民军医出版社,2001,183-214.
[67]Pedersen I,Kremer M,Judd J et al.Androgens regulate bone resorption activity of isolated osteoclsts in vitro[J].Proe Natl Acad Sci U S A 1999,96(2):505-10.
[68]郭世绂.骨质疏松基础与临床[M].天津:天津科技出版社.2001.535.
[69]侯淑琴,肖占森.绝经妇女骨代谢变化及雌激素对骨代谢的影响[J].中国骨质疏松杂志,2000,6(1):72 73.
[70]张俐,王占朝,张安桢,等.男性原发性骨质疏松症中医证型的实质探讨[J].中国中医骨伤科杂志,2004,12(3):1.
[71]金世鑫.男性骨质疏松症诊断和治疗[J].中国骨质疏松杂志,2000,6(3):72-75.
[72]邸明芝,庞炜,王治伦.部分细胞因子在原发性骨质疏松症发病机理中的作用[J].中国骨质疏松杂志,2000,6(2):87-90.
[73]赵燕玲,丁桂芝,刘忠厚,等.原发性骨质疏松症的发病机理[J].中国骨质疏松杂志,1998,4(4)73-77.
[74]The development of the WHO quality of life assessment instrument[S].Geneva,WHO,1993:1.
[75]Badia X,Prieto I,Roset M,et al development of the ECOS-16clinical questionnaine for the assessment of the quality of life in patients with osteoporosis[J].Med Clin,2000,114(Suppl 3):68-75.
[76]黄如娇,韦坚,黄美蔼,等.骨质疏松症患者的生活质量研究及护理干预影响[J].中国全科医学,2006,(11):1798-1800.
[77]Deborah J.Cook,Gordon H,et al.Quality of life issues in women with vertebral fractures due to osteoporosis[J].Arthritis and Rheumatism,1993,36(6):750.
[78]黄如娇,韦坚,黄美蔼,等.骨质疏松症患者的生活质量研究及护理干预影响[J].中国全科医学,2006,(11):1798-1800.
[79]Jarvinen M,Kannus P.Injury of an extremity as a risk factor for the development of osteoporosis[J].J Bone Jonit Surg,1997,79A,263-276.
[80]陈金标,秦林林.骨质疏松症与遗传[J].中国骨质疏松杂志,2000,6(2):89-91.
[81]王洪复.骨质疏松症的诊断[J].国际内分泌代谢杂志,2006,26(4):285-288.
[82]Lane JM,Riley EH,Wirganowicz PZ.Osteoporosis:Diagnosis and Treatment[J].J Bone Joint Surg,1996,78A:618.
[83]ChisholmMA,Mulloy A1.Management of osteoporosis in the elderly[J].J Geriatric Drug Therapy,1996,11(1):5-15.
[84]李险峰.骨质疏松症的临床表现、检查及诊断[J].新医学,2007,38(1):18-11.
[85]李景学.骨矿物质影像学研究的新趋向[J].中华放射学杂志,1996,30:56-58.
[86]张兴雨,秦沛.腰椎和髋部骨密度测定在骨质疏松诊断上的相关性分析[J].中国临床康复,2005,9(3):198-199.
[87]Liu B,Wang C,Yang M,et al.Clinical value of urinary deoxypyridionllne excretion in postmenopausal osteoporosis[J].Chinese Journal Osteoporosis,2002,8:43-46(in Chinese).
[88]Xiao Y,Zhang J,Hua B,e tal.Experimental Study of QCT in predicting the Strength of Vertebra[J].Chinese Journal of Medical Imaging Technology,2002,18:625-627(in Chinese).
[89]Zhang J,Deng J,Ouyang Q,et al.Acomparative study of bone mineral density and bone metabolic markers in primary osteoporosis[J].Chinese Journal of Osteoporosis,2OOS,11:319-324(in Chinese).
[90]King X,Ren A,Yang J,et al.Application of procollagen IN-Termina extension peptides in the diagonosis of Osteoporosis[J].Acta Universitatis Medicinalis Anhui,1999,34(5):361-363.
[91]Garnero P,Ferreras M,Karsdal MA,et al.Thetype Ⅰ collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation[J].J Bone Miner Res,2003,18:859-867.
[92]Charles P,Mosekilde L,RisteliL,et al.Assessment of bone remodeling using biochemical indicators of type I collagen synthesis and degredation:relation to calcium kinetics[J].Bone Miner,1994,24:81-94.
[93]Zhang J,Deng J,Ouyang Q,et al.Acomparative study of bone mineral density and bone metabolic markers in primary osteoporosis[J].Chinese Journal of Osteoporosis,2OO5,11:319-324(in Chinese).
[94]许士凯,陈再智.老年生理学与病理学研究进展(之一)[J].现代中西医结合杂志2005,14(2):146-148
[95]王洪复,于名香.老年人成骨细胞形成功能的衰退与治疗[J].国外医学内分泌学分册2003,23(2):79-81.
[96]Parfitt AM.The mechanism of coupling:a role for the vasculature[J].Bone,2000,26:319.
[97]王维,何成奇.骨质疏松症与衰老的关系[J].中国临床康复,2005,9(7):93-95.
[98]Wyllie AH,Kerr JER,Currie AR et al.Celld eath:thesig-nificance of apoptosis[J]IntRevCytol,1980,68(1):25-307.
[99]KleinRF,Fausti KA,Carlos AS,et al.Ethanol inhibits human osteoblastic cell proliferation[J].Alcohol Clin ExpRes,1996,20(3):572-578.
[100]Ookawa K,Tisuchida S,Adachi J,et al.Differentiation inducedby RB expression and apoptosis induced by p53 expression in an osteosarcoma cell line[J].Oncogene,1997,14(12):1389-1396.
[101]Kawakami A,Nakane PK,Matsuka N,et al.Fas and Faslig and interaction is necessary for human osteoblast apoptosis[J].J Bone Mine rRes,1997,12(10):1637-1646.
[102]Hil 1PA,Tumber A,Meikle MC,et al.Multiple extracellular signal spromote osteoblast survival and apoptosis[5].Endocrinology,1997,138(9):3849-3858.
[103]Jilka RL,Weinstein T,Bellido AM,et al.Osteoblast programmed cell death:modulation by growth factors and cytokines[J].J Bone Miner Res,1998,13(3):793-802.
[104]Robert S,Weistein RL,Michae P,et al.Inhibition of osteoblastogenesis and Promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids[J].J ClinInvest,1998,102(2):274-282.
[105]Pittenger MF,Mackay AM,Beck SC et al.Multilineage potential of adult human mesenchymal stem cells[J].Science,1999,284:143-147.
[106]王和鸣,王力.巴戟天对骨髓基质细胞向成骨细胞方向分化影响的实验研究.福建中医学院院报,2004,14(3):16.
[107]郑良朴,李椭,王和鸣.补骨合剂对体外培养骨髓基质细胞分化影响的观察[J].福建中医学院学报,2003,13(6):33.
[108]徐展望,张建新,李军等.骨碎补提取液对兔骨髓基质细胞增殖的影响[J].中医正骨,2005,17(4):1-3.
[109]邓展生,张璇,邹冬青,等.骨碎补各种提取成分对人骨髓间充质干细胞的影响[J].中国现代医学杂志,2005,15(16):2426-2429.
[110]王华松,陈庄洪,罗永湘.髓内脂肪细胞促骨髓基质细胞凋亡的实验研究[J].中国骨质疏松杂志,2005,11(3):325-328.
[111]张兴凯,杨庆铭,邓廉大,等.骨质疏松症成骨细胞生物学特征的体外研究[J].中国骨质琉松杂志,2004,10(1):48-50.
[112]Mazess RB.Fracture risk:a role for compact bone[J].Calcif Tissue Int,1990,47:191-193.
[1]Eriksen EF,Langdahl BL.The pathogensis of osteoporosis[J].Horm one Research,1997,48(Supple.5):78-82.
[2]张兴凯,杨庆铭,邓廉夫等.骨质疏松症成骨细胞生物学特征的体外研究[J].中国骨质疏松杂志,2004,10(1):48-50.
[3]MazessRB.Fracture risk:a role for compact bone[J].Calcif Tissue Int,1990,47:191-193.
[4]Weinstein RS,Jilka RL,Parfitt AM,etal.Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids:potential mechanisms of their deleterious effect on bone[J].J Clin Invest,1998,102:274-282.
[5]李靖,王全平.细胞凋亡与骨质疏松关系的研究进展[J]中华骨科杂志,2001,21(5):305-307.
[6]沈霖,杜靖远,周丕琪等.补肾法对TNF-a诱导新生大鼠成骨细胞凋亡的保护作用[J].中国中医骨伤科杂志,2000,8(1)2-4.
[7]韩清民,施佳平,林一峰等.肿瘤坏死因子α诱导大鼠成骨细胞凋亡与中药骨康的干预效应[J].中国临床康复,2005,9(23):170-172.
[8]王玉东,李大金,朱影等.补肾宁心方对小鼠成骨细胞的增殖和抗凋亡作用[J].中国中西医结合杂志,2004,24(3):230-233.
[9]李楠,王和鸣,林旭等.补骨合剂对全反式维甲酸诱导的骨髓基质细胞凋亡的保护作用[J]中西医结合学报2002(5):367-371.
[10]高晓燕,孟艳彬,赵春颖.补肾中约对成骨样细胞UMRl06增殖的影响[J].承德医学院学报,2002,19(1):7-9.
[11]李娟,吴伟康,余克强.不同实验浓度补肾中药血清对人成骨细胞增殖及分化的促进作用[J].中国临床康复,2005,9(19):82-84.
[12]曲耀华,刘彬,厉永强.补肾方剂对大鼠成骨样细胞增殖及相关酶类的影响[J].山东中医杂志,2003,22(7):424-425.
[13]lian JB,Gunderg CM,Osteocalcin.Biochemical consideration and clinical applications[J].Clin Orthop Rel Res,1987,226(2):267-270.
[14]邢国胜,谈志龙,王淑云等.补肾健骨汤对成骨细胞增殖及碱性磷酸酶、骨钙素合成的影响[J].中草药,2001,32(11):1020-1022.
[15]李冬华,朱飞鹏.补肾中药对体外培养成骨细胞增殖和功能的影响[J].中药药理与临床,2005,21(2):32-34.
[16]王俊勤,胡有谷,郑洪军等.淫羊藿甙对体外培养成骨细胞增殖和分化的影响[J].中国临床康复,2002,6(9):1307-1308.
[17]Bellows CG,Aubin JEM,Rntosa ME.Mineralized bone nodules formed in vitro from enzymatically released rat calvaria populations[J].Calcif Tissue Jnt,1986,38:143
[18]唐井钢,李娟,吴贺勇.喂饲补肾中药大鼠的血清对成骨细胞的生物学作用[J].第一军医大学学报,2004,24(11):1248-1250.
[19]李娟,吴伟康,孙炜等.补肾中药对人成骨细胞钙离子摄取和钙化能力的影响[J].第一军医大学学报,2004,24(12):1359-1361.
[20]马金,姜涌,郑洪新,密骨颗粒含药血清对大鼠成骨样细胞增殖及Ca~(2+)/CaM信使1005-1007系统影响的研究[J].中医药学刊,2004,22(6):1005-1007.
[21]Erlebacher A,Derrnck R.Increased expression of TGF-beta in osteoblast results anosteoporosis like phenotype[J].Journal of Cell Biology 1996,132:192-199.
[22]邸明芝,庞炜,王治伦.部分细胞因子在原发性骨质疏松症发病机理中的作用[J].中国骨质疏松杂志,2000,6(2):87-90.
[23]沈霖,杜靖远,曾晖等.补肾方对成骨细胞生长因子TGF-β 1mRNA表达的影响[J].中医正骨,2001,13(5):3-5.
[24]任艳玲,郑洪新,杜松.补肾健脾药物血清对大鼠成骨细胞TGF-β1表达的影响[J].辽宁中医杂志,2005,32(2):100-102.
[25]Heldin CH,MiyazonoK,ten Dijke P.TGF-β signaling from cell membrarn to nucleus through SMAD proteins[J].Nature,1997,390:465-471.
[26]任艳玲,郑洪新,杜松.补肾健脾药物血清对大鼠成骨细胞Smad2 mRNA表达影响的研究[J].中医药学刊,2005,23(4):618-620.
[27]雪原,王沛,齐清会等.淫羊藿甙对成骨细胞Smad4 mRNA作用的实验研究[J].中华骨科杂志,2005,25(2):119-123.
[28]任艳玲,郑洪新,杜松.补肾健脾药物血清对人鼠成骨细胞信号转导分子Smad4表达的影响[J.]中国老年学杂志,2005,25(3):289-291.
[1]王和鸣,葛继荣,田金洲,等.强骨胶囊治疗原发性骨质疏松症临床试验[J].中药新药与临床药理,2004,15(4):284-287.
[2]刘剑刚,谢雁鸣,赵晋宁,等.骨碎补总黄酮胶囊对实验性骨质疏松症和镇痛作用的影响[J].中国实验方剂学杂志,2004,10(5):31-34.
[3]谢雁鸣,许勇钢,赵晋宁,等.骨碎补总黄酮对去卵巢大鼠骨密度和细胞因子IL-6、IL-4、TNF α水平的影响[J].中国中医基础医学杂志,2004,10(1):34-37.
[4]马克昌,高子范,冯坤,等.骨碎补提取液对小鸡骨发育的促进作用[J].中医正骨,1990,2(4):7.
[5]马克昌,朱太咏,刘鲜姑,等.骨碎补注射液对培养中鸡胚骨原基钙化的促进作用[J].中国中药杂志,1995,20(3):178.
[6]谢雁鸣,赵晋宁,张文军强等.骨胶囊抗维甲酸所致大鼠骨质疏松症的实验研究[J].中药新药与临床药理,1998,9(4):217-220.
[7]谢雁鸣,赵晋宁,丁会,等.强骨胶囊抗去势大鼠骨质疏松症的实验研究[J].中国中医药科技,2000,7(3):151-152.
[8]Kalu DN,Liu CC,Hardin RR et al.The aged rat model of ovarian hormone deficiency bone loss[J].Endocrinology,1989,124(1):7.
[9]谢雁鸣,鞠大宏,赵晋宁.骨碎补总黄酮对去卵巢大鼠骨密度和骨组织形态计量学影响[J].中国中药杂志,2004,29(4):343-346
[10]马中书,王蕊,邱明才,等.四种补肾中药对去卵巢大鼠骨质疏松骨形态的作用[J].中华妇产科杂志,1999,34(2):82-85。
[11]张兴凯,杨庆铭,邓廉夫,等.骨质疏松症成骨细胞生物学特征的体外研究[J].中国骨质疏松杂志,2004,10(1):48-50.
[12]Mazess RB.Fracture risk:a role for compact bone[J].Calcif Tissue Int,1990,47:191-193
[13]谢雁鸣,秦林林,邓文龙,等.骨碎补总黄酮对成骨细胞体外培养作用的机制研究[J].中华中医药杂志,2005,20(3):161-162.
[14]唐琪,陈莉丽,严杰.骨碎补提取物促小鼠成骨细胞株MC3T3-E1细胞增殖、分化和钙化作用的研究[J].中国中药杂志,2004,29(2):164-168.
[15]Pittenger MF,Mackay AM,Beck SC et al.Multilineage potential of adult human mesenchymal stem cells[J].Science,1999,284:143-147.
[16]王和鸣,王力.巴戟天对骨髓基质细胞向成骨细胞方向分化影响的实验研究[J].福建中医学院院报,2004,14(3):16.
[17]郑良朴,李椭,王和鸣.补骨合剂对体外培养骨髓基质细胞分化影响的观察[J].福建中医学院学报,2003,13(6):33
[18]徐展望,张建新,李军等.骨碎补提取液对兔骨髓基质细胞增殖的影响[J].中医正骨,2005,17(4):1-3.
[19]邓展生,张璇,邹冬青,等.骨碎补各种提取成分对人骨髓间充质干细胞的影响[J].中国现代医学杂志,2005,15(16):2426-2429.
[20]Eriksen EF,Langdahl BL.The pathogensis of osteoporosis[J].Horm one Research,1997,48(Supple.5):78-82.
[21]樊粤光,黄永明,曾意荣,等.骨碎补提取液对体外分离破骨细胞性骨吸收的作用[J].中国中医骨伤科杂志,2003,11(6):4-6.
[22]刘金文,黄永明,许少健,等.中药骨碎补对大鼠骨髓破骨细胞体外培养的影响[J].中医研究,2005,18(7):5-7.
[23]邸明芝,庞炜,王治伦.部分细胞因子在原发性骨质疏松症发病机理中的作用[J].中国骨质疏松杂志,2000,6(2):87-90.
[24]谢雁鸣,许勇钢,赵晋宁,等.骨碎补总黄酮对去卵巢大鼠骨密度和细胞因子.IL-6、IL-4、 TNFα水平的影响[J].中国中医基础医学杂志,2004,10(1):34-37.
[25]Erlebacher A,Derrnck R.Increased expression of TGF-beta in osteoblast results anosteoporosis like phenotype[J].Journal of Cell Biology 1996,132:192-199.
[26]王华松,许申明.骨碎补对骨折愈合中TGF-β1表达的影响[J].中国中医骨伤科杂志,2001,9(4):10-13.
[27]谢雁鸣,张露,王智,等.骨碎补总黄酮对去卵巢大鼠基因水平的影响[J].中国中药杂志,2005,30(14):1092-1095.