从肾防治糖皮质激素性骨质疏松症的理论与临床研究
|
摘要
骨质疏松症(osteoporosis, OP)是一种以骨量降低和骨组织微结构破坏为特征,导致骨脆性增加和易于骨折的代谢性骨病。按病因分为原发性和继发性两类。糖皮质激素性骨质疏松症是一种继发性骨质疏松症。随着糖皮质激素在临床的广泛应用,目前糖皮质激素性骨质疏松症(glucocorticoid-induced osteoporosis, GIO))的发病率仅次于绝经后及老年性骨质疏松症而居第三位。
系统性红斑狼疮(SLE)是一种表现有多系统损害的慢性系统性自身免疫病,其血清具有以抗核抗体为代表的多种自身抗体。糖皮质激素仍是系统性红斑狼疮的主要药物之一。
中医认为,糖皮质激素为阳刚之品,大剂量皮质激素长期应用,易导致肾阴亏虚,当撤减激素时,肾阳又因失去“纯阳”之品的“助养”而导致肾阳虚衰。其病因类似于“药毒”,病机特点为“阳常有余,阴常不足”。针对糖皮质激素的特性,临床我们根据糖皮质激素使用量采用以滋阴或温阳为主进行干预,防治糖皮质激素性骨质疏松症的发生。
目的：
观察从肾防治糖皮质激素性骨质疏松症的临床疗效,客观评价从肾防治系统性红斑狼疮糖皮质激素性骨质疏松症的临床疗效和安全性。
方法：
根据简单随机、对照、非盲的临床试验原则,收集符合诊断纳入标准和排出标准的SLE患者80例。将80例患者随机分为两组,治疗组予金匮肾气丸加减中药联合碳酸钙D3、骨化三醇胶丸治疗,对照组予碳酸钙D3、骨化三醇胶丸治疗。疗程6个月。于试验观察6个月后次日检测两组各项指标,包括血钙、血磷、尿钙、尿磷、免疫反应性甲状旁腺激素(IPTH)、血清碱性磷酸酶(ALP)、骨钙素(BGP).25-(OH) D3、骨密度(BMD),分析各检测指标,并进行统计学分析。
结果：
血Ca、尿P比较,两组间差异无显著性；血P水平比较,治疗组显著高于对照组(P<0.05)；尿Ca比较,治疗组显著低于对照组(P<0.05)。IPTH水平比较,治疗组低于对照组,治疗组与对照组比较有统计学意义；25-(OH)D3及ALP水平比较,治疗组高于对照组,两组比较有统计学意义(P<0.05)。治疗组BGP和BMD均高于对照组,两组比较有统计学意义(P<0.05)。观察过程中,无病例脱落。治疗期间,治疗组与对照组在治疗过程中无一例患者出现不良反应。
结论：
从肾论治,以金匮肾气丸加减结合西药防治糖皮质激素性骨质疏松症比单用西药疗效更显著,在改善骨转换、骨代谢、骨密度等指标方面疗效更为确切。同时,有着良好的安全性,没有明显的毒副作用发生。
Osteoporosis (OP) is a metabolic disease characterized by bone mass reducing and micro-structure of bone tissue destroying. It's divided into two kinds according to the cause. One is primary and the other is secondary. Glucocorticoid induced osteoporosis(GIO) is the third one which is inferior to post menopausal and aged osteoporosis.
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease, manifesting damages in multiple systems, with multiple self-antibodies characterized by anti-nuclear antibodies in the serum. Glucocorticoid is still one of the common medicines used to cure systemic lupus erythematosus.
In traditional chinese medicine, glucocorticoid is one kind of yang materials. A mass of glucocorticoid used for a long term will induce kidney yin defficiency. When glucocorticoid is reduced, kidney yang will be insufficient due to losing warm nourishment of the yang material. The cause of glucocorticoid is similar to "drug toxin". The pathogenesis is that "yang is always sufficient while yin is always insufficient."
Clinically we adopt the ways of nourishing yin or warm yang to interfere and to prevent and treat glucocorticoid induced osteoporosis based on the amoumt of glucocorticoid.
Objective
To observe the clinical effect of the prevention and treatment of glucocorticoid induced osteoporosis through kidney. To evaluate the clinical effect and the safety of the prevention and treatment of glucocorticoid induced osteoporosis through kidney in systemic lupus erythematosus.
Methods
Based on the clinical test principled of random, control and open-label,80patients suffering from systemic lupus erythematosus were divided into two groups:the patients in the treatment group(n=40) were given the changed decoction of Jinkui Shenqi pills combined with the tablets of calcium carbonate and vitaraine D3and the soft capsule of calcitriol. The treatment lasted2months. After treatment, the metabolic indexes such as blood calcium, blood phosphor, urine calcium, urine phosphor were observed and tested. IPTH、ALP、 BGP、25-(OH) D3and BMD were also tested. Analyzed and statistically analyzed the test results.
Results
There was no significant difference in blood calcium and urine phosphor between the treatment group and the control group(P>0.05). The level of blood phosphor,25-(OH)D3and ALP were higher in the treatment group than that in the control group(P<0.05). The level of urine calcium and IPTH in the treatment group were lower than that in the control group ((P<0.05). The treatment group had lower BGP and BMD than the control group((P<0.05). There was no patient falling off from the two groups and there was no any side effect in the two groups.
Conclusion
Based on the treatment through kidney, the decoction of Jingui Shenqi pills combined with western medicines had better therapeutic effects than the western medicine used only. Especially prevention and treatment through kidney had specific improvement in the bone turnover, bone metabolism, bone mineral density, and so on. The combination of the decoction with western medicines has better clinical effects and safety in preventing and treating GIO in SLE.
系统性红斑狼疮(SLE)是一种表现有多系统损害的慢性系统性自身免疫病,其血清具有以抗核抗体为代表的多种自身抗体。糖皮质激素仍是系统性红斑狼疮的主要药物之一。
中医认为,糖皮质激素为阳刚之品,大剂量皮质激素长期应用,易导致肾阴亏虚,当撤减激素时,肾阳又因失去“纯阳”之品的“助养”而导致肾阳虚衰。其病因类似于“药毒”,病机特点为“阳常有余,阴常不足”。针对糖皮质激素的特性,临床我们根据糖皮质激素使用量采用以滋阴或温阳为主进行干预,防治糖皮质激素性骨质疏松症的发生。
目的：
观察从肾防治糖皮质激素性骨质疏松症的临床疗效,客观评价从肾防治系统性红斑狼疮糖皮质激素性骨质疏松症的临床疗效和安全性。
方法：
根据简单随机、对照、非盲的临床试验原则,收集符合诊断纳入标准和排出标准的SLE患者80例。将80例患者随机分为两组,治疗组予金匮肾气丸加减中药联合碳酸钙D3、骨化三醇胶丸治疗,对照组予碳酸钙D3、骨化三醇胶丸治疗。疗程6个月。于试验观察6个月后次日检测两组各项指标,包括血钙、血磷、尿钙、尿磷、免疫反应性甲状旁腺激素(IPTH)、血清碱性磷酸酶(ALP)、骨钙素(BGP).25-(OH) D3、骨密度(BMD),分析各检测指标,并进行统计学分析。
结果：
血Ca、尿P比较,两组间差异无显著性；血P水平比较,治疗组显著高于对照组(P<0.05)；尿Ca比较,治疗组显著低于对照组(P<0.05)。IPTH水平比较,治疗组低于对照组,治疗组与对照组比较有统计学意义；25-(OH)D3及ALP水平比较,治疗组高于对照组,两组比较有统计学意义(P<0.05)。治疗组BGP和BMD均高于对照组,两组比较有统计学意义(P<0.05)。观察过程中,无病例脱落。治疗期间,治疗组与对照组在治疗过程中无一例患者出现不良反应。
结论：
从肾论治,以金匮肾气丸加减结合西药防治糖皮质激素性骨质疏松症比单用西药疗效更显著,在改善骨转换、骨代谢、骨密度等指标方面疗效更为确切。同时,有着良好的安全性,没有明显的毒副作用发生。
Osteoporosis (OP) is a metabolic disease characterized by bone mass reducing and micro-structure of bone tissue destroying. It's divided into two kinds according to the cause. One is primary and the other is secondary. Glucocorticoid induced osteoporosis(GIO) is the third one which is inferior to post menopausal and aged osteoporosis.
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease, manifesting damages in multiple systems, with multiple self-antibodies characterized by anti-nuclear antibodies in the serum. Glucocorticoid is still one of the common medicines used to cure systemic lupus erythematosus.
In traditional chinese medicine, glucocorticoid is one kind of yang materials. A mass of glucocorticoid used for a long term will induce kidney yin defficiency. When glucocorticoid is reduced, kidney yang will be insufficient due to losing warm nourishment of the yang material. The cause of glucocorticoid is similar to "drug toxin". The pathogenesis is that "yang is always sufficient while yin is always insufficient."
Clinically we adopt the ways of nourishing yin or warm yang to interfere and to prevent and treat glucocorticoid induced osteoporosis based on the amoumt of glucocorticoid.
Objective
To observe the clinical effect of the prevention and treatment of glucocorticoid induced osteoporosis through kidney. To evaluate the clinical effect and the safety of the prevention and treatment of glucocorticoid induced osteoporosis through kidney in systemic lupus erythematosus.
Methods
Based on the clinical test principled of random, control and open-label,80patients suffering from systemic lupus erythematosus were divided into two groups:the patients in the treatment group(n=40) were given the changed decoction of Jinkui Shenqi pills combined with the tablets of calcium carbonate and vitaraine D3and the soft capsule of calcitriol. The treatment lasted2months. After treatment, the metabolic indexes such as blood calcium, blood phosphor, urine calcium, urine phosphor were observed and tested. IPTH、ALP、 BGP、25-(OH) D3and BMD were also tested. Analyzed and statistically analyzed the test results.
Results
There was no significant difference in blood calcium and urine phosphor between the treatment group and the control group(P>0.05). The level of blood phosphor,25-(OH)D3and ALP were higher in the treatment group than that in the control group(P<0.05). The level of urine calcium and IPTH in the treatment group were lower than that in the control group ((P<0.05). The treatment group had lower BGP and BMD than the control group((P<0.05). There was no patient falling off from the two groups and there was no any side effect in the two groups.
Conclusion
Based on the treatment through kidney, the decoction of Jingui Shenqi pills combined with western medicines had better therapeutic effects than the western medicine used only. Especially prevention and treatment through kidney had specific improvement in the bone turnover, bone metabolism, bone mineral density, and so on. The combination of the decoction with western medicines has better clinical effects and safety in preventing and treating GIO in SLE.
引文
[1]安胜军,李恩,等.雌激素受体基因多态性与女性绝经后骨质疏松症中医辨证分型关系的研究[J].中国中西医结合杂志,2000,20(12):907.
[2]周修通.“龟鹿二仙汤”治疗骨质疏松症病例临床观察[J].江苏中医,2001,22(6):28.
[3]谢林,姚共和,郭振球,等.健脾养胃法治疗骨质疏松症初探[J].湖南中医学院学报,1996,16(4)：7-9.
[4]王玲玲,刘跃光,李祥炜,等.绝经后骨质丢失病因病机的中医学分析[J].南京中医药大学学报,1999,15(6)：324-325.
[5]刘秋生.原发性骨质疏松症中医病机初探[J].光明医,2000,5(5)：5-6.
[6]卢心宇.辨证治疗老年性骨质疏松症[J].福建中医学院学报,1994,(1)：25-26.
[7]眭承志,范燕妮.老年性骨质疏松血瘀病机的微观分子生物学研究[J].中国骨质疏松杂志,2010,16(5)：325-330.
[8]张荣华,朱晓峰,等.脾肾两虚兼血瘀与原发性骨质疏松关系的探讨[J].四川中医,2003,21(5):11-12.
[9]郭芳.益肾养肝法治疗骨质疏松症患者30例临床观察[J].现代诊断与治疗,2003,14(5)：269-269.
[10]刘峰,梁翔,彭太平,等.中医药辨证治疗骨质疏松症128例[J].实用中西医结合临床,2005,5(4)： 52.
[11]张华,朱洪民,宁显明,等.原发性骨质疏松症病因病机探析[J].国医论坛,2001,16(2)：24-25.
[12]罗毅文,刘海全,李爽,等.骨质疏松症的中医治则[J].中国临床康复,2003,7(30):4170.
[13]朱运平.骨质疏松症从脾肾论治及相关机理探讨[J].中医药临床杂志,2004,16(6)：589-590.
[14]黄绍卫,吴浩祥,等.浅谈骨质疏松症的病机与经方治疗[J].中医药导报,2006,12(12)：13-14.
[15]陈丽琛,唐年亚,邱幸凡,等.骨质疏松症的病因病机及其防治探讨[J].山西中医,2007,23(1)：4-6.
[16]许建安,杨挺,邸振福.壮骨益髓汤治疗原发性骨质疏松症疗效观察[J].中医正骨,2000,12(5): 17-18.
[17]许正发,代玉金.右归丸治疗骨质疏松96例[J].国医论坛,2012,17(2)：50.
[18]孙湘.加味左归丸治疗骨质疏松症腰背痛临床疗效观察[J].中国中医骨伤科杂志,2001,10(5)：36-37.
[19]胡文,刘荷梅,等.青娥丸对实验性骨质疏松代谢的调节作用[J].中国临床药学杂志,2002,10(5)：36-37.
[20]崔巍.拟壮骨通痹汤治疗绝经后骨质疏松性骨痛临床观察[J].实用中西医结合杂志,2002,2(4)：30-31.
[21]王运泽,王建萍,李秀珍,等.益肾补骨片治疗老年性骨质疏松症临床研究[J].山东中医杂 志,2000,19(10)：590-591.
[22]朱小华,赵仓焕,等.从脾胃论治骨质疏松症[J].新中医,2004,36(12):3-4.
[23]钱会南.中医脾本质现代研究概况[J].中国中医药信息杂志,2002,9(7):85-87.
[24]朱凌凌,童瑶,陈慧娟,等.脾的中西医学比较研究[J].浙江中医杂志,2006,41(1):1-6.
[25]邵敏,黄宏兴,庄洪,等.骨康防治骨质疏松拆方的初步研究[J].中国中医骨伤科杂志,2000,8(2)：7-11.
[26]水正,水森,等.益肾祛疲法治疗老年骨质疏松症[J].上海预防医学杂志,1995,7(5):230.
[27]李芳芳,李恩,冬晓旭,等.补肾健脾和活血化瘀方药对去卵巢大鼠骨质疏松的比较性研究[J],中国骨质疏松杂志,1998,4(1):529.
[28]张俊中,蔡余力.补肾益气活血法治疗绝经后骨质疏松的实验研究[J].中国骨伤,2002,15(4)：217-219.
[29]谭清武,陈俊文.补肾健脾活血方药对老年骨质疏松大鼠血清IL-6的影响[J].中国中医药科技,2002,9(6)：331-339.
[30]张丽.隔物灸调节老年骨密度的研究[J].中医函授通讯,1997,16(1)：35.
[31]刘献祥,吴明霞.针灸对原发性骨质疏松症影响的实验和临床研究[J].中国骨伤,2000,13(9)：519-521.
[32]艾双春,路雪婧,廖方正,等.神阙穴贴药对原发性骨质疏松症超声穿透速度的影响[J].中国针灸,2003,23(1)：17-18.
[33]赵婷婷,严碧歌,等.超声诊断松质骨的研究进展[J].海南医学院学报,2009,15(9)：1179-1181.
[34]杨沛彦,苏友新,许书亮,等.中国人原发性骨质疏松症患病率及影响因素的研究进展[J].中国临床康复,2002,6(10)：2904-2905.
[35]何伟,张俐,王维佳,等.骨病临床研究[M].北京：北京科学技术出版社,2006：323-335.
[36]Kanis JA, Johnello, Oden A, et al.Ten year probilities of osteoporotic fractures according to BMD and diagnostic shreshods[J]. Osteoporos Int,2001,12(12):989-995.
[37]Keil DP, Demissie S, Dupuis J, et al. Genome-wide association with bone mass and geomety in the Framingham Heart Study[J].BMC Med Genet,8 Suppl 1:S14
[38]Richards JB, Rivadeneira F, Inouye M, et al. Bone mineral desity, osteoporosis and osteoporotic fracture:a genome-wide association study[J]. Lancet,200i,371(9623): 1505-1512.
[39]Wong PK, Christie JJ, Wark JD. The effects of smoking on bone health[J]. Clin Sci(Lond),2007;113(5):233-241.
[40]Parkhouse WS,Coup land DC, L I C,et al.IGF-1 bio2 availability is increased by resistance training in older women with lowbone mineral density[J]. Mech Ageing Dev,2000;113(2):75-83.
[41]Saitoglu M, Ardicoglu 0, Ozqocmen S, et al. Osteoporosis risk factors and association with somatotypes in males[J]. Arch Med Res,2007;38(7):746-751.
[42]黄武,刘幼硕,等.老年性骨质疏松症的诊断及治疗要点[J].中华老年医学杂志,2005,24(12)：939-941.
[43]QINL, LIZA J, RAGGATT, et al. Parathyroid hormone:a double-edged sword for bone metabolism [J]. Trends Endocrinology Metabolism,2004; 15(2):60-65.
[44]NEER R M, AENAUD C D, ZANCHETTA J R, et al.Effect of parathyroid hormone(1-34) on fractures and bonemineral density in postmenopausal women with osteoporosis[J]. N Engl J Med,2001;344(10):1434-1441.
[45]Wallach S, Farley JR, Baylink DJ, et al. Effects of calcitonin on bone quality and osteoblastic function[J]. Calcif Tissue Int,1993;52(5):335-339.
[46]冉博,武宇赤,哈斯,等.原发性骨质疏松症的病因研究进展[J].内蒙古医学院学报,2008,12(30)：157-160.
[47]SchoppetM, PreissnerKT, HofbauerLC. Rank ligand and osteoprotegerin paracrine regulators of bone metabolism and vascular function[J].J Arterioscler Thromb Vase Biol,2002;22(4):549-553.
[48]Cao J, Venton L, Sakata T, et al. Expression of rand and OPG correlates with age-rlated bone loss in male C57BL/6 mice[J].JB one RES,2003;18(2):270-272.
[49]Kostenuik PJ, Morony S, Capparelli C, et al. OPG and PTH-(1-34)have additive effects on bone density and mechanical strength in osteopenic ovariectomized rats[J].Endocrinology,2001;142(10):4295-4304.
[50]Carani C, Oin K, Simoni M, et al. Effect of testosterone and estradiol in a man witharomatase deficiency:Briefrepoet[J]. N Engl J Med,1997, (337):91-95.
[51]Lubahn DB, Meyer JS, Golding TS, et al. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene[J].Proc Natl Acad Sci,USA,1993, (90):11162.
[52]Roger B, et al. Androgens and sketletal homeostasis in men. Osteoporosis up date[C]. Third International congress on Osteoporosis,1992.32.
[53]Alu E. The Localization of androgen receptors in human bone[J].J Clin Endocrinol Mctab,1997, (82):3493.
[54]Horowate MC. Cytokines and estrogen in bone:anti-osteoporosis[J]. Science, 1993, (26):626.
[55]孙磊.骨再建局部调节因子与骨质疏松[J].国外医学.老年分册,1999,20(2)：52-55.
[56]Pabio F, Copas ES, Harman SM, et al. Serum IGF-bingding 23 is related to IGF-1, but not to spontaneous GH release in healthy old men[J]. Endocrine Rev,1990, (11):558.
[57]庄辉.酒精性肝病的流行病学[J].中华肝脏病杂志,2003,11(11)：689.
[58]Turner RT. Skeletal response to alcohol[J]. Alcohol Clin Exp Res,2000,24(11): 1693-1701.
[59]Maran A, Zhang M, Spelsberg, TC, et al. The dose response effects of ethanol on the human fetal osteoblastic celline[J].J Bone Miner Res,2001,16(2)L270-276.
[60]Gong Z, Wezeman FH, Inhibitory effect of alcohol on osteogenic differentiation ih human bone marrow-derived mesenchymal stem cell[J]. Alcohol Clin Exp Res,2004,28:468-479.
[61]李杰,李月白,王义生,等.酒精对骨髓基质细胞成脂与成骨分化的影响中华骨科杂志[J].中华骨科杂志,2003,23：493-495.
[62]陈金标,秦林林,李光伟,等.386例健康男性骨密度与吸烟的关系[J].中华预防医学杂志,2001,35(3)：149-151.
[63]战行程.熬夜吸烟是“疲马加鞭”[J].今日科苑,2006, (3)：48.
[64]夏维波骨.质疏松症的防治[J].中国全科医学,2010,13(1B)：118-120.
[65]Cosman R, Lindsay R. Therapeutic potential of parathyroid hormone[J]. Curr Osteoporos Rep,2004,2:5-11.
[66]Dempser DW,Cosman F, Kurland ES, et al. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis:a paired biopsy study[J].J BoneMiner Res,2001,16:1846-1853.
[67]Celiker R, Arslan S. Comparison of serum insulin-like growth factor-1 and growth hormone level sinosteoporotic and non-osteoporotic postmenapausal women[J]. Rheumatol Int,2000,19:205-208.
[68]李文平,吴祥根,全东琴,等.骨质疏松症的药物治疗进展[J].解放军药学学报,2007,23(6)：444-447.
[69]Silvestrini G, Mocetti P, BallantiP et al. Cytochemical demonstration of the glucocorticoid receptor in skeletal cells of the rat. Endocr Res,1999,25:117.
[70]Weinstein RS, Jika RL, Parfitt AM et al. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest,1998,102:274.
[71]张波,姚小丹.糖皮质激素所致骨质疏松的研究现状及治疗[J].肾脏病与透析。肾移植杂志,2002,11(4)：368-373.
[72]Smith E,Redman RA, Logg CR et al.Glucocorticoids inhibit developmental stage-specific osteoblast cell cycle. Dissociation of cyclin A-cyclin-de pendent kinase 2 from E2F4-p130 complexes. J Biol Che m,2000,275:19992.
[73]Silvestrini G, Mocetti P, BallantiP et al. Cytochemical demonstration of the glucocorticoid receptor in skeletal cells of the rat. Endocr Res,1999,25:117.
[74]Swolin D, Brantsing C, Matej ka G et al. Cortis ol decreases IGF-1 mRNA levels in human osteoblast like cells. J Endocrinol,1996,149:397.
[75]Kumar R. Glucocorticoid-induced osteoporosis. Curr Opin Nephrol Hypertens,2001, 10:589.
[76]Bergendahl M, Veldhuis JD. Altered pulsatile gonadot ropin signaling in nutritional deficiency in the male. Trends Endocrionol Metab,1995,6:145
[77]Cosman F, Nieves J, Herbert J et al.High-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skelet on. J Bone Min Res,1994,9:1097.
[78]Reid IR, Watt ie DJ, Evans MD et al. Testosterone therapy in glucocorticoid-treated men. Arch Int Med,1996,156:1173
[79]Grecu EO, Weinshelbaum A, Simmons R. Effective therapy of glucocorticoid-induced osteoporosis with medroxyprogesterone actate. Calcif Tissue Int,1990,46:294
[80]Gruber CJ, Tschugguel W, Schneeberger C et al. Production and actions of estrogens. N Engl J Med,2002,346:340
[81]Buckley LM,Leib ES, Cartuaro KS et al. Calcium and vitami n D3 supple-mentation prevents bone loss in the spine secondry to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double blind, placebo-controlled rial.Ann Int ern Med,1996,125:961
[82]Sa mbrook P, Bi rmingham J, Kell y P et al. Prevent ion of cort icosteroid osteoporosis. A comparis on of calci um, calcitri ol, and calct i oni n. N Engl J Med, 1993,328:1747
[83]Lakotos P, Nagy Z, Kis s L et al. Prevent i on of corticosteroid-i nduced osteoporosis by alfacalcidol. Z Rheumatol,2000,59(Suppl 1):48
[84]Sambrook P.Henderson NK, Keogh A et al. Effect of calcitrion on bone loss after cardiac or lung transplantation. J Bone Min Res,2000,15:1818
[85]Lane NE, Sanchez S,Modi n GW et al. Parathyroid hormone treatment can reverse corticosteroid induced osteoporosis. Results of a randomized controlled clinical t rial. J Clin Invest,1998,102:1627
[86]Fan SL-S, Cunnningham J. Bisphosphonates in renal osteodystrophy. Curr Opin Nephrol Ilypert ens,2001,10:581
[87]Struys A, Snelder AA,Mulder H. Cyclical etidronate reverses bone loss of the spine and proximal femur in pat ie'nt swith establis hed corticoteroid-induced ostoporosi s. Am J Med,1995,99:235
[88]Skingle SJ,Moore DJ, Crisp AJ. Cyclical etidronate increases lumbar spine bone density in patients on long-term glucocorticosteroid therapy. Int J Clin Pract,1997, 51:364
[89]Adachi JD, Bensen WG, Brown J et al. Intermittent etidronate therapy to prevent corticosteroi d -induced osteoporosis. N Engl J Med,1997,337:382
[90]Bousten Y, Jamart J, Es selinck W. Primary prevent ion of glucocorticoid-induced osteoporos is with intermittent intravenous pamidronate:a randomized trial. Calcif Tissue Int,1997,61:266
[91]Saag KG, Emkey R, Sc hnitzer TJ e t al. Alendronate for the prevent-ion andtreatment of glucocorticoid -induced osteoporosis. N Engl J Med,1998,339:292
[92]Reid DM, Hughes RA, Laan RF et al. Efficacy and safety of daily ri se -dronate in the treatment of corticosteroid-induced osteoporosi s in men and women:a randomized trial. European Corticos teroid-Induced Osteoporosis Treatment Study. J Bone Min Res, 2000,15:1006
[93]Markowitz GS, Appel GB, Fine PL et al. Collapsing focal segmental glomerulosclerosis following t reatment with high-dose pamidronate. J Am Soc Nephrol,2001,12:1164.
[94]陈凯,姜春燕.中药减轻糖皮质激素副作用的研究[J].中华中医药杂志,2005,20(10)：636
[95]金明柱,郑洪新.中医药干预糖皮质激素副作用的研究[J].辽宁中医药大学学报,2007,9(2)： 23
[96]李雷.肾病综合征激素副作用的中医辨治[J].河南中医,2005,25(10)：36
[97]张美莲.加昧六味地黄汤可减少激素的副作用[J].山西医药杂志,2007,36(6)： 574
[98]黄访英.分阶段应用中药减轻激素治疗肾病综合征副作用的临证体会[J].中国中西医结合肾病杂志,2004,5(3)：174
[99]钟卓衡卢娟娟,蔡楚丹.中西医结合治疗原发性肾病综合征疗效及激素副作用观察[J].中国中西医结合肾病杂志,2002,3(2)：91
[100]王岸俊. 中药对肾病综合征应用激素所致副作用的影响[J].湖北中医杂志,2001,23(3) ： 6
[101]郜枫,周贤桂.中药对肾病综合征激素疗法副作用的疗效观察[J].湖北民族学院学报·医学版,2001,18(4)：28
[102]刘杭卫.中药拮抗皮质激素副作用58例分析[J].中国现代应用药学,2001,18(2)：165
[103]彭洁,包海燕,卢海东.中药治疗糖皮质激素副作用58例[J].中国医学研究与临床,2007,5(1) ： 48
[104]李英侠,董卫.原发性肾病综合征78例中药纠正激素副作用的疗效观察. 山西医药杂志,2007,36(5)：466
[105]谢明映. 肾病方防治。 肾病综合征激素疗法副作用临床观察[J].四川中医,2002, 20(5) ： 39
[106]刘竹生,陈贤黄雪萍.益肾汤防治激素副作用临床分析[J]。实用中医药杂志,2007,23(3)：141
[107]张杰. 麦味地黄汤加味治疗激素副作用5例[J].江西中医药,2002,33(5)： 48
[108]朱起之,赵树进.知母皂甙对糖皮质激素副作用的影响[J].实用医学杂志,2001,17(7)：583
[109]顾锡炳,陈浩坤,刘海肃,等.大剂量强力宁防止糖皮质激素治疗重型肝炎主要副作用的临床观察[J].现代医药卫生,2001,17(4)：265.
[110]沈自尹.有关证与神经内分泌免疫网络的研究[J].中医药学刊,2003,21(1):10
[111]董竞成,蔡定芳.肾虚与科学[M].北京：人民卫生出版社,2007:262
[112]黄建华,沈自尹,刘小雨,等. 淫羊藿总黄酮拮抗皮质酮大鼠肾上腺皮质细胞凋亡的研究[J].中医药学刊,2006,24(9)：1664.
[113]吴铁,崔燎,张志平,等.淫羊霍对抗肾上腺皮质激素不良反应的实验研究[J].中国中药杂志,1996,21(12)：748—751.
[114]吴剑静,温利平,吴云刚,等.仙灵骨葆胶囊治疗糖皮质激素性骨质疏松的临床疗效观察[J].中国骨伤,2009,22(3)：193—195
[115]刘梅洁. 滋补肾阴法对糖皮质激素所致骨质疏松大鼠Wn t信号传导的影响[D].北京：中国中医科学院,2009.
[116]沈培芝,陈东煜,张戈,等.补肾方防治地塞米松致雄性大鼠骨质疏松及其生化机制探讨[J].中国中西医结合杂志,1998,18(5)：290-292.
[117]康天济,蒋爱丽. 补肾实骨汤治疗糖皮质激素性骨质疏松的实验研究[J]. 中医药学报,2009,37(4)：32-35
[118]刘玲萍,李捷,孙平,等.补肾壮骨中药对糖皮质激素诱发骨质疏松大鼠的干预作用[J].中药材,2010,33(4)：593-595.
[119]吴剑静,温利平,吴云刚,等.仙灵骨葆胶囊治疗糖皮质激素性骨质疏松症的临床疗效观察[J]中国骨伤,2009,22(3)：193-195
[120]崔燎,邹丽宜,刘钰瑜,等.丹参水提物和丹参素促进成骨细胞活性和防治泼尼松所致大鼠骨质疏松[J].中国药理学通报,2004,20(3)：286-291
[121]肖柳斌,刘国雄,王晖,等.丹参水提液对抗大鼠泼尼松性骨质疏松的作用研究[J]中国临床药理学与治疗学,2008,13(1)：94-98.
[122]苏开鑫,谢华,王宏芬,等.牡蛎肉提取物对类固醇性骨质疏松大鼠骨代谢的影响[J].中国自然医学杂志,2009,11(2)：97-99
[123]Shi XM, Blair HC, Yang X, et al. Tandemrepeat of C/EBP binding sites mediates PPARr2 gene transcription in glucocorticoid-induced adipocyte differentiation[J]. J Cell Biochem,2000,76:518-527.
[124]金明柱,郑洪新.糖皮质邀素诱导肾虚骨质疏松症大鼠骨组织PPAR r2与TGF-β1/Smads的m R N A及蛋白表达[D].辽宁中医药大学,2007
[125]Canalis E, Mazziotti G,Giustina A, et al. Glucocorticoid-induced osteoporosis:pathophysiology and therapy[J]. Osteoporos Int,2007,18:1319-1328.
[126]]周乐,崔燎,吴铁,等.淫羊藿对。肾阳虚雄性大鼠肾脏和股骨BMP-7表达的影响[J].中国骨质疏松杂志,2008,14(2)：90-94
[127]Wang FS, Ko JY, Yeh DW, et al. Modulation of Dick-kopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss[J]. Endocrinology,2008,149:1793-1801.
[128]刘梅洁,鞠大宏.滋补肾阴法对糖皮质激素所致骨质疏松大鼠Wn t信号传导的影响[D].中国中医科学院,2009
[129]刘尚全,杨颖,周丽斌,等.淫羊藿苷逆转地塞米松抑制成骨细胞分化及其机制[J].中华内分泌代谢杂志,2006,22(3)：218-221
[130]高曦,于雪峰.健骨冲剂防治糖皮质激素性骨质疏松的实验研究[D].黑龙江中医药大学,2007
[131]高曦,李洪涛,娄宏君,等.骨蚀灵胶囊对糖皮质激素性骨质疏松症Ⅰ型胶原m R N A表达影响的实验研究[J].中国临床保健杂志,2010,13(4)：377-379
[132]夏雄智,樊粤光.补肾法对激素干预成骨样细胞作用的差异蛋白初步分析及相关研究[D].广州中医药大学,2007.
[133]Hofbauer LC,Gori F, Riggs BL. Stimulation of osteoprotegerin ligand and inhibition of osteioprotegerin production by glucocorticoids in human osteoblastic lineage cells:potential paracrine mechanisms of glucocorticoid-induced osteoporosis[J]. Endocrinology,1999,140:4382-4389.
[134]Kondo T, Ktiazawa R, Yamaguchi A, et al. Dexamethasone promotes osteoclastogenesis by inhibiting osteoprotegerin through multiple levels[J]. J Cell Biochem,2008,103:335-345.
[135]Hofbauer LC, Zeitz U, Schoppet M, et al. Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL[J].ArthritiRheum,2009,60:1427-1437.
[136]王建伟,马勇,尹恒.金匮肾气丸联用葡萄糖酸钙对原发性骨质疏松症疼痛临床疗效观察[J].辽宁中医药大学学报,2012,14(2)：5-6.
[137]王建伟,郭杨,周信,等.金匮肾气丸联用葡萄糖酸钙对去势大鼠骨微结构的影响[J]).中国老年学杂志,2012,32：313-315.
[138]Pons F, Peris P, Guanabens N, et al. The effect of system i c lupus erythematosus and long-ter m steroid therapy on bone mass in premenopausal women. Br JRheum,1995,34 742-746
[139]Lahita R G., System ic lupus ery thematosus. Second Ed. NewYork:Church i1,1992:922~923.
[140]Barbara P L, Law rence G R. Glucocorticoid induced osteoporosis pathogenesis and management. Amn Intern M ed,1990,112:352~359
[141]李恩,孔德娟,杨学辉,等.补肾方药对骨质疏松防治的实验研究[J].中国骨质疏松杂志,2002,8(2)：166-170.
[142]刘和娣,李星海,林富山,等.补肾中药对骨质疏松大鼠多指标及骨形态计量学的影响[J].中国老年学杂志,2002,22:512-513.
[143]杜靖远,胡光亮,夏志道,等.补肾密骨液对体外培养新生大鼠颅骨成骨细胞增殖的影响[J].中华实验外科杂志,1998,15(5)：465
[144]沈霖,杜靖远,赵海波.补肾法对IL-1诱导的破骨细胞性骨吸收及破骨细胞MMP-9的影响[J].中医正骨,1999,11(7)：3
[145]沈霖,杜靖远,常晖,等.补肾方对成骨细胞生长因子TGF-β 1m RNA表达的影响[J].中医正骨,2001,13(5)：3
[146]崔家鹏,郑洪新,刘景峰,等.补肾中药对肾虚骨质疏松症大鼠红细胞膜PKC, Ca2+-Mg2+-AT P酶活性影响的实验研究[J].中国骨质疏松杂志,1997,3(3)：66.
[147]张莹雯,陈友香,夏振信.金匮肾气丸对老年雌性大鼠一氧化氮、性激素的影响[J].中成药,2003：25(3)：252-253.
[148]马勇,王建伟,周玲玲,等.金匮肾气丸联合葡萄糖酸钙对去势大鼠骨代谢的影响[J].中国老年学杂志,2012,32：4227-4228.
[149]赵春江.金匮肾气丸与六味地黄丸异同[J].四川中医,2011,29(12): 118-119.
[150]陈涛.山茱萸水提液对骨质疏松模型小鼠骨形态学影响[J].天津药学,2003,15(4):5-6.
[151]杨茗,季晖,张树平,等.知母皂苷元对成骨细胞活性和破骨细胞分化及功能的影响[J].中国药物大学学报,2009,40(6)：544-546.
[152]Nian H, Qin L, Chen W, et al. Protective effect of steroidal saponins from rhizome of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats[J]. Acta Pharmacol Sinica,2006,27(6):728.
[153]Qin L, Han T, Zhang Q, et al. Antiosteoporotic chemical constituents from Er-Xian Decoction, a tr- aditional Chinese herbal formula [J]. J Ethnopharmacol,2008,118(2): 271.
[154]丁茜,张凤秋.淫羊藿苷对人牙周膜细胞表达核因子kB受体激活蛋白配体和护骨因子的影响[L].中华口腔医学杂志,2013,48(2)：68-71.
[155]高峰,莫新民,李劲平.淫羊藿苷治疗去势大鼠骨质疏松症基因表达谱分析[J].中国中医药信息杂志,2013,20(2)：43-45.
[156]吕明波,刘兴炎,葛宝丰,等.淫羊藿苷对破骨细胞活性的影响[J].中国骨伤,2007,20(8)：529-531.
[157]杨肖红,张昆.淫羊藿对糖尿病骨质疏松患者骨保护素水平的影响[J].山东医药,2010,50(49)：66-67.
[158]郭海玲,赵咏芳,王翔,等.淫羊藿苷对人成骨细胞增殖及OPG蛋白表达的实验研究[J].中国骨伤,2011,24(7)：585-588.
[159]杨荣平,寿清耀,涂永勤,等.补骨脂提取物对体外培养新生大鼠颅骨成骨细胞的影响[J].中药新药与临床药理,2007,18(1)：32-34.
[160]眭承志.骨碎补总黄酮治疗骨质疏松症作用机理实验研究进[J].中华中医药学刊,2010,28(6):1272-1274.
[2]周修通.“龟鹿二仙汤”治疗骨质疏松症病例临床观察[J].江苏中医,2001,22(6):28.
[3]谢林,姚共和,郭振球,等.健脾养胃法治疗骨质疏松症初探[J].湖南中医学院学报,1996,16(4)：7-9.
[4]王玲玲,刘跃光,李祥炜,等.绝经后骨质丢失病因病机的中医学分析[J].南京中医药大学学报,1999,15(6)：324-325.
[5]刘秋生.原发性骨质疏松症中医病机初探[J].光明医,2000,5(5)：5-6.
[6]卢心宇.辨证治疗老年性骨质疏松症[J].福建中医学院学报,1994,(1)：25-26.
[7]眭承志,范燕妮.老年性骨质疏松血瘀病机的微观分子生物学研究[J].中国骨质疏松杂志,2010,16(5)：325-330.
[8]张荣华,朱晓峰,等.脾肾两虚兼血瘀与原发性骨质疏松关系的探讨[J].四川中医,2003,21(5):11-12.
[9]郭芳.益肾养肝法治疗骨质疏松症患者30例临床观察[J].现代诊断与治疗,2003,14(5)：269-269.
[10]刘峰,梁翔,彭太平,等.中医药辨证治疗骨质疏松症128例[J].实用中西医结合临床,2005,5(4)： 52.
[11]张华,朱洪民,宁显明,等.原发性骨质疏松症病因病机探析[J].国医论坛,2001,16(2)：24-25.
[12]罗毅文,刘海全,李爽,等.骨质疏松症的中医治则[J].中国临床康复,2003,7(30):4170.
[13]朱运平.骨质疏松症从脾肾论治及相关机理探讨[J].中医药临床杂志,2004,16(6)：589-590.
[14]黄绍卫,吴浩祥,等.浅谈骨质疏松症的病机与经方治疗[J].中医药导报,2006,12(12)：13-14.
[15]陈丽琛,唐年亚,邱幸凡,等.骨质疏松症的病因病机及其防治探讨[J].山西中医,2007,23(1)：4-6.
[16]许建安,杨挺,邸振福.壮骨益髓汤治疗原发性骨质疏松症疗效观察[J].中医正骨,2000,12(5): 17-18.
[17]许正发,代玉金.右归丸治疗骨质疏松96例[J].国医论坛,2012,17(2)：50.
[18]孙湘.加味左归丸治疗骨质疏松症腰背痛临床疗效观察[J].中国中医骨伤科杂志,2001,10(5)：36-37.
[19]胡文,刘荷梅,等.青娥丸对实验性骨质疏松代谢的调节作用[J].中国临床药学杂志,2002,10(5)：36-37.
[20]崔巍.拟壮骨通痹汤治疗绝经后骨质疏松性骨痛临床观察[J].实用中西医结合杂志,2002,2(4)：30-31.
[21]王运泽,王建萍,李秀珍,等.益肾补骨片治疗老年性骨质疏松症临床研究[J].山东中医杂 志,2000,19(10)：590-591.
[22]朱小华,赵仓焕,等.从脾胃论治骨质疏松症[J].新中医,2004,36(12):3-4.
[23]钱会南.中医脾本质现代研究概况[J].中国中医药信息杂志,2002,9(7):85-87.
[24]朱凌凌,童瑶,陈慧娟,等.脾的中西医学比较研究[J].浙江中医杂志,2006,41(1):1-6.
[25]邵敏,黄宏兴,庄洪,等.骨康防治骨质疏松拆方的初步研究[J].中国中医骨伤科杂志,2000,8(2)：7-11.
[26]水正,水森,等.益肾祛疲法治疗老年骨质疏松症[J].上海预防医学杂志,1995,7(5):230.
[27]李芳芳,李恩,冬晓旭,等.补肾健脾和活血化瘀方药对去卵巢大鼠骨质疏松的比较性研究[J],中国骨质疏松杂志,1998,4(1):529.
[28]张俊中,蔡余力.补肾益气活血法治疗绝经后骨质疏松的实验研究[J].中国骨伤,2002,15(4)：217-219.
[29]谭清武,陈俊文.补肾健脾活血方药对老年骨质疏松大鼠血清IL-6的影响[J].中国中医药科技,2002,9(6)：331-339.
[30]张丽.隔物灸调节老年骨密度的研究[J].中医函授通讯,1997,16(1)：35.
[31]刘献祥,吴明霞.针灸对原发性骨质疏松症影响的实验和临床研究[J].中国骨伤,2000,13(9)：519-521.
[32]艾双春,路雪婧,廖方正,等.神阙穴贴药对原发性骨质疏松症超声穿透速度的影响[J].中国针灸,2003,23(1)：17-18.
[33]赵婷婷,严碧歌,等.超声诊断松质骨的研究进展[J].海南医学院学报,2009,15(9)：1179-1181.
[34]杨沛彦,苏友新,许书亮,等.中国人原发性骨质疏松症患病率及影响因素的研究进展[J].中国临床康复,2002,6(10)：2904-2905.
[35]何伟,张俐,王维佳,等.骨病临床研究[M].北京：北京科学技术出版社,2006：323-335.
[36]Kanis JA, Johnello, Oden A, et al.Ten year probilities of osteoporotic fractures according to BMD and diagnostic shreshods[J]. Osteoporos Int,2001,12(12):989-995.
[37]Keil DP, Demissie S, Dupuis J, et al. Genome-wide association with bone mass and geomety in the Framingham Heart Study[J].BMC Med Genet,8 Suppl 1:S14
[38]Richards JB, Rivadeneira F, Inouye M, et al. Bone mineral desity, osteoporosis and osteoporotic fracture:a genome-wide association study[J]. Lancet,200i,371(9623): 1505-1512.
[39]Wong PK, Christie JJ, Wark JD. The effects of smoking on bone health[J]. Clin Sci(Lond),2007;113(5):233-241.
[40]Parkhouse WS,Coup land DC, L I C,et al.IGF-1 bio2 availability is increased by resistance training in older women with lowbone mineral density[J]. Mech Ageing Dev,2000;113(2):75-83.
[41]Saitoglu M, Ardicoglu 0, Ozqocmen S, et al. Osteoporosis risk factors and association with somatotypes in males[J]. Arch Med Res,2007;38(7):746-751.
[42]黄武,刘幼硕,等.老年性骨质疏松症的诊断及治疗要点[J].中华老年医学杂志,2005,24(12)：939-941.
[43]QINL, LIZA J, RAGGATT, et al. Parathyroid hormone:a double-edged sword for bone metabolism [J]. Trends Endocrinology Metabolism,2004; 15(2):60-65.
[44]NEER R M, AENAUD C D, ZANCHETTA J R, et al.Effect of parathyroid hormone(1-34) on fractures and bonemineral density in postmenopausal women with osteoporosis[J]. N Engl J Med,2001;344(10):1434-1441.
[45]Wallach S, Farley JR, Baylink DJ, et al. Effects of calcitonin on bone quality and osteoblastic function[J]. Calcif Tissue Int,1993;52(5):335-339.
[46]冉博,武宇赤,哈斯,等.原发性骨质疏松症的病因研究进展[J].内蒙古医学院学报,2008,12(30)：157-160.
[47]SchoppetM, PreissnerKT, HofbauerLC. Rank ligand and osteoprotegerin paracrine regulators of bone metabolism and vascular function[J].J Arterioscler Thromb Vase Biol,2002;22(4):549-553.
[48]Cao J, Venton L, Sakata T, et al. Expression of rand and OPG correlates with age-rlated bone loss in male C57BL/6 mice[J].JB one RES,2003;18(2):270-272.
[49]Kostenuik PJ, Morony S, Capparelli C, et al. OPG and PTH-(1-34)have additive effects on bone density and mechanical strength in osteopenic ovariectomized rats[J].Endocrinology,2001;142(10):4295-4304.
[50]Carani C, Oin K, Simoni M, et al. Effect of testosterone and estradiol in a man witharomatase deficiency:Briefrepoet[J]. N Engl J Med,1997, (337):91-95.
[51]Lubahn DB, Meyer JS, Golding TS, et al. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene[J].Proc Natl Acad Sci,USA,1993, (90):11162.
[52]Roger B, et al. Androgens and sketletal homeostasis in men. Osteoporosis up date[C]. Third International congress on Osteoporosis,1992.32.
[53]Alu E. The Localization of androgen receptors in human bone[J].J Clin Endocrinol Mctab,1997, (82):3493.
[54]Horowate MC. Cytokines and estrogen in bone:anti-osteoporosis[J]. Science, 1993, (26):626.
[55]孙磊.骨再建局部调节因子与骨质疏松[J].国外医学.老年分册,1999,20(2)：52-55.
[56]Pabio F, Copas ES, Harman SM, et al. Serum IGF-bingding 23 is related to IGF-1, but not to spontaneous GH release in healthy old men[J]. Endocrine Rev,1990, (11):558.
[57]庄辉.酒精性肝病的流行病学[J].中华肝脏病杂志,2003,11(11)：689.
[58]Turner RT. Skeletal response to alcohol[J]. Alcohol Clin Exp Res,2000,24(11): 1693-1701.
[59]Maran A, Zhang M, Spelsberg, TC, et al. The dose response effects of ethanol on the human fetal osteoblastic celline[J].J Bone Miner Res,2001,16(2)L270-276.
[60]Gong Z, Wezeman FH, Inhibitory effect of alcohol on osteogenic differentiation ih human bone marrow-derived mesenchymal stem cell[J]. Alcohol Clin Exp Res,2004,28:468-479.
[61]李杰,李月白,王义生,等.酒精对骨髓基质细胞成脂与成骨分化的影响中华骨科杂志[J].中华骨科杂志,2003,23：493-495.
[62]陈金标,秦林林,李光伟,等.386例健康男性骨密度与吸烟的关系[J].中华预防医学杂志,2001,35(3)：149-151.
[63]战行程.熬夜吸烟是“疲马加鞭”[J].今日科苑,2006, (3)：48.
[64]夏维波骨.质疏松症的防治[J].中国全科医学,2010,13(1B)：118-120.
[65]Cosman R, Lindsay R. Therapeutic potential of parathyroid hormone[J]. Curr Osteoporos Rep,2004,2:5-11.
[66]Dempser DW,Cosman F, Kurland ES, et al. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis:a paired biopsy study[J].J BoneMiner Res,2001,16:1846-1853.
[67]Celiker R, Arslan S. Comparison of serum insulin-like growth factor-1 and growth hormone level sinosteoporotic and non-osteoporotic postmenapausal women[J]. Rheumatol Int,2000,19:205-208.
[68]李文平,吴祥根,全东琴,等.骨质疏松症的药物治疗进展[J].解放军药学学报,2007,23(6)：444-447.
[69]Silvestrini G, Mocetti P, BallantiP et al. Cytochemical demonstration of the glucocorticoid receptor in skeletal cells of the rat. Endocr Res,1999,25:117.
[70]Weinstein RS, Jika RL, Parfitt AM et al. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest,1998,102:274.
[71]张波,姚小丹.糖皮质激素所致骨质疏松的研究现状及治疗[J].肾脏病与透析。肾移植杂志,2002,11(4)：368-373.
[72]Smith E,Redman RA, Logg CR et al.Glucocorticoids inhibit developmental stage-specific osteoblast cell cycle. Dissociation of cyclin A-cyclin-de pendent kinase 2 from E2F4-p130 complexes. J Biol Che m,2000,275:19992.
[73]Silvestrini G, Mocetti P, BallantiP et al. Cytochemical demonstration of the glucocorticoid receptor in skeletal cells of the rat. Endocr Res,1999,25:117.
[74]Swolin D, Brantsing C, Matej ka G et al. Cortis ol decreases IGF-1 mRNA levels in human osteoblast like cells. J Endocrinol,1996,149:397.
[75]Kumar R. Glucocorticoid-induced osteoporosis. Curr Opin Nephrol Hypertens,2001, 10:589.
[76]Bergendahl M, Veldhuis JD. Altered pulsatile gonadot ropin signaling in nutritional deficiency in the male. Trends Endocrionol Metab,1995,6:145
[77]Cosman F, Nieves J, Herbert J et al.High-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skelet on. J Bone Min Res,1994,9:1097.
[78]Reid IR, Watt ie DJ, Evans MD et al. Testosterone therapy in glucocorticoid-treated men. Arch Int Med,1996,156:1173
[79]Grecu EO, Weinshelbaum A, Simmons R. Effective therapy of glucocorticoid-induced osteoporosis with medroxyprogesterone actate. Calcif Tissue Int,1990,46:294
[80]Gruber CJ, Tschugguel W, Schneeberger C et al. Production and actions of estrogens. N Engl J Med,2002,346:340
[81]Buckley LM,Leib ES, Cartuaro KS et al. Calcium and vitami n D3 supple-mentation prevents bone loss in the spine secondry to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double blind, placebo-controlled rial.Ann Int ern Med,1996,125:961
[82]Sa mbrook P, Bi rmingham J, Kell y P et al. Prevent ion of cort icosteroid osteoporosis. A comparis on of calci um, calcitri ol, and calct i oni n. N Engl J Med, 1993,328:1747
[83]Lakotos P, Nagy Z, Kis s L et al. Prevent i on of corticosteroid-i nduced osteoporosis by alfacalcidol. Z Rheumatol,2000,59(Suppl 1):48
[84]Sambrook P.Henderson NK, Keogh A et al. Effect of calcitrion on bone loss after cardiac or lung transplantation. J Bone Min Res,2000,15:1818
[85]Lane NE, Sanchez S,Modi n GW et al. Parathyroid hormone treatment can reverse corticosteroid induced osteoporosis. Results of a randomized controlled clinical t rial. J Clin Invest,1998,102:1627
[86]Fan SL-S, Cunnningham J. Bisphosphonates in renal osteodystrophy. Curr Opin Nephrol Ilypert ens,2001,10:581
[87]Struys A, Snelder AA,Mulder H. Cyclical etidronate reverses bone loss of the spine and proximal femur in pat ie'nt swith establis hed corticoteroid-induced ostoporosi s. Am J Med,1995,99:235
[88]Skingle SJ,Moore DJ, Crisp AJ. Cyclical etidronate increases lumbar spine bone density in patients on long-term glucocorticosteroid therapy. Int J Clin Pract,1997, 51:364
[89]Adachi JD, Bensen WG, Brown J et al. Intermittent etidronate therapy to prevent corticosteroi d -induced osteoporosis. N Engl J Med,1997,337:382
[90]Bousten Y, Jamart J, Es selinck W. Primary prevent ion of glucocorticoid-induced osteoporos is with intermittent intravenous pamidronate:a randomized trial. Calcif Tissue Int,1997,61:266
[91]Saag KG, Emkey R, Sc hnitzer TJ e t al. Alendronate for the prevent-ion andtreatment of glucocorticoid -induced osteoporosis. N Engl J Med,1998,339:292
[92]Reid DM, Hughes RA, Laan RF et al. Efficacy and safety of daily ri se -dronate in the treatment of corticosteroid-induced osteoporosi s in men and women:a randomized trial. European Corticos teroid-Induced Osteoporosis Treatment Study. J Bone Min Res, 2000,15:1006
[93]Markowitz GS, Appel GB, Fine PL et al. Collapsing focal segmental glomerulosclerosis following t reatment with high-dose pamidronate. J Am Soc Nephrol,2001,12:1164.
[94]陈凯,姜春燕.中药减轻糖皮质激素副作用的研究[J].中华中医药杂志,2005,20(10)：636
[95]金明柱,郑洪新.中医药干预糖皮质激素副作用的研究[J].辽宁中医药大学学报,2007,9(2)： 23
[96]李雷.肾病综合征激素副作用的中医辨治[J].河南中医,2005,25(10)：36
[97]张美莲.加昧六味地黄汤可减少激素的副作用[J].山西医药杂志,2007,36(6)： 574
[98]黄访英.分阶段应用中药减轻激素治疗肾病综合征副作用的临证体会[J].中国中西医结合肾病杂志,2004,5(3)：174
[99]钟卓衡卢娟娟,蔡楚丹.中西医结合治疗原发性肾病综合征疗效及激素副作用观察[J].中国中西医结合肾病杂志,2002,3(2)：91
[100]王岸俊. 中药对肾病综合征应用激素所致副作用的影响[J].湖北中医杂志,2001,23(3) ： 6
[101]郜枫,周贤桂.中药对肾病综合征激素疗法副作用的疗效观察[J].湖北民族学院学报·医学版,2001,18(4)：28
[102]刘杭卫.中药拮抗皮质激素副作用58例分析[J].中国现代应用药学,2001,18(2)：165
[103]彭洁,包海燕,卢海东.中药治疗糖皮质激素副作用58例[J].中国医学研究与临床,2007,5(1) ： 48
[104]李英侠,董卫.原发性肾病综合征78例中药纠正激素副作用的疗效观察. 山西医药杂志,2007,36(5)：466
[105]谢明映. 肾病方防治。 肾病综合征激素疗法副作用临床观察[J].四川中医,2002, 20(5) ： 39
[106]刘竹生,陈贤黄雪萍.益肾汤防治激素副作用临床分析[J]。实用中医药杂志,2007,23(3)：141
[107]张杰. 麦味地黄汤加味治疗激素副作用5例[J].江西中医药,2002,33(5)： 48
[108]朱起之,赵树进.知母皂甙对糖皮质激素副作用的影响[J].实用医学杂志,2001,17(7)：583
[109]顾锡炳,陈浩坤,刘海肃,等.大剂量强力宁防止糖皮质激素治疗重型肝炎主要副作用的临床观察[J].现代医药卫生,2001,17(4)：265.
[110]沈自尹.有关证与神经内分泌免疫网络的研究[J].中医药学刊,2003,21(1):10
[111]董竞成,蔡定芳.肾虚与科学[M].北京：人民卫生出版社,2007:262
[112]黄建华,沈自尹,刘小雨,等. 淫羊藿总黄酮拮抗皮质酮大鼠肾上腺皮质细胞凋亡的研究[J].中医药学刊,2006,24(9)：1664.
[113]吴铁,崔燎,张志平,等.淫羊霍对抗肾上腺皮质激素不良反应的实验研究[J].中国中药杂志,1996,21(12)：748—751.
[114]吴剑静,温利平,吴云刚,等.仙灵骨葆胶囊治疗糖皮质激素性骨质疏松的临床疗效观察[J].中国骨伤,2009,22(3)：193—195
[115]刘梅洁. 滋补肾阴法对糖皮质激素所致骨质疏松大鼠Wn t信号传导的影响[D].北京：中国中医科学院,2009.
[116]沈培芝,陈东煜,张戈,等.补肾方防治地塞米松致雄性大鼠骨质疏松及其生化机制探讨[J].中国中西医结合杂志,1998,18(5)：290-292.
[117]康天济,蒋爱丽. 补肾实骨汤治疗糖皮质激素性骨质疏松的实验研究[J]. 中医药学报,2009,37(4)：32-35
[118]刘玲萍,李捷,孙平,等.补肾壮骨中药对糖皮质激素诱发骨质疏松大鼠的干预作用[J].中药材,2010,33(4)：593-595.
[119]吴剑静,温利平,吴云刚,等.仙灵骨葆胶囊治疗糖皮质激素性骨质疏松症的临床疗效观察[J]中国骨伤,2009,22(3)：193-195
[120]崔燎,邹丽宜,刘钰瑜,等.丹参水提物和丹参素促进成骨细胞活性和防治泼尼松所致大鼠骨质疏松[J].中国药理学通报,2004,20(3)：286-291
[121]肖柳斌,刘国雄,王晖,等.丹参水提液对抗大鼠泼尼松性骨质疏松的作用研究[J]中国临床药理学与治疗学,2008,13(1)：94-98.
[122]苏开鑫,谢华,王宏芬,等.牡蛎肉提取物对类固醇性骨质疏松大鼠骨代谢的影响[J].中国自然医学杂志,2009,11(2)：97-99
[123]Shi XM, Blair HC, Yang X, et al. Tandemrepeat of C/EBP binding sites mediates PPARr2 gene transcription in glucocorticoid-induced adipocyte differentiation[J]. J Cell Biochem,2000,76:518-527.
[124]金明柱,郑洪新.糖皮质邀素诱导肾虚骨质疏松症大鼠骨组织PPAR r2与TGF-β1/Smads的m R N A及蛋白表达[D].辽宁中医药大学,2007
[125]Canalis E, Mazziotti G,Giustina A, et al. Glucocorticoid-induced osteoporosis:pathophysiology and therapy[J]. Osteoporos Int,2007,18:1319-1328.
[126]]周乐,崔燎,吴铁,等.淫羊藿对。肾阳虚雄性大鼠肾脏和股骨BMP-7表达的影响[J].中国骨质疏松杂志,2008,14(2)：90-94
[127]Wang FS, Ko JY, Yeh DW, et al. Modulation of Dick-kopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss[J]. Endocrinology,2008,149:1793-1801.
[128]刘梅洁,鞠大宏.滋补肾阴法对糖皮质激素所致骨质疏松大鼠Wn t信号传导的影响[D].中国中医科学院,2009
[129]刘尚全,杨颖,周丽斌,等.淫羊藿苷逆转地塞米松抑制成骨细胞分化及其机制[J].中华内分泌代谢杂志,2006,22(3)：218-221
[130]高曦,于雪峰.健骨冲剂防治糖皮质激素性骨质疏松的实验研究[D].黑龙江中医药大学,2007
[131]高曦,李洪涛,娄宏君,等.骨蚀灵胶囊对糖皮质激素性骨质疏松症Ⅰ型胶原m R N A表达影响的实验研究[J].中国临床保健杂志,2010,13(4)：377-379
[132]夏雄智,樊粤光.补肾法对激素干预成骨样细胞作用的差异蛋白初步分析及相关研究[D].广州中医药大学,2007.
[133]Hofbauer LC,Gori F, Riggs BL. Stimulation of osteoprotegerin ligand and inhibition of osteioprotegerin production by glucocorticoids in human osteoblastic lineage cells:potential paracrine mechanisms of glucocorticoid-induced osteoporosis[J]. Endocrinology,1999,140:4382-4389.
[134]Kondo T, Ktiazawa R, Yamaguchi A, et al. Dexamethasone promotes osteoclastogenesis by inhibiting osteoprotegerin through multiple levels[J]. J Cell Biochem,2008,103:335-345.
[135]Hofbauer LC, Zeitz U, Schoppet M, et al. Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL[J].ArthritiRheum,2009,60:1427-1437.
[136]王建伟,马勇,尹恒.金匮肾气丸联用葡萄糖酸钙对原发性骨质疏松症疼痛临床疗效观察[J].辽宁中医药大学学报,2012,14(2)：5-6.
[137]王建伟,郭杨,周信,等.金匮肾气丸联用葡萄糖酸钙对去势大鼠骨微结构的影响[J]).中国老年学杂志,2012,32：313-315.
[138]Pons F, Peris P, Guanabens N, et al. The effect of system i c lupus erythematosus and long-ter m steroid therapy on bone mass in premenopausal women. Br JRheum,1995,34 742-746
[139]Lahita R G., System ic lupus ery thematosus. Second Ed. NewYork:Church i1,1992:922~923.
[140]Barbara P L, Law rence G R. Glucocorticoid induced osteoporosis pathogenesis and management. Amn Intern M ed,1990,112:352~359
[141]李恩,孔德娟,杨学辉,等.补肾方药对骨质疏松防治的实验研究[J].中国骨质疏松杂志,2002,8(2)：166-170.
[142]刘和娣,李星海,林富山,等.补肾中药对骨质疏松大鼠多指标及骨形态计量学的影响[J].中国老年学杂志,2002,22:512-513.
[143]杜靖远,胡光亮,夏志道,等.补肾密骨液对体外培养新生大鼠颅骨成骨细胞增殖的影响[J].中华实验外科杂志,1998,15(5)：465
[144]沈霖,杜靖远,赵海波.补肾法对IL-1诱导的破骨细胞性骨吸收及破骨细胞MMP-9的影响[J].中医正骨,1999,11(7)：3
[145]沈霖,杜靖远,常晖,等.补肾方对成骨细胞生长因子TGF-β 1m RNA表达的影响[J].中医正骨,2001,13(5)：3
[146]崔家鹏,郑洪新,刘景峰,等.补肾中药对肾虚骨质疏松症大鼠红细胞膜PKC, Ca2+-Mg2+-AT P酶活性影响的实验研究[J].中国骨质疏松杂志,1997,3(3)：66.
[147]张莹雯,陈友香,夏振信.金匮肾气丸对老年雌性大鼠一氧化氮、性激素的影响[J].中成药,2003：25(3)：252-253.
[148]马勇,王建伟,周玲玲,等.金匮肾气丸联合葡萄糖酸钙对去势大鼠骨代谢的影响[J].中国老年学杂志,2012,32：4227-4228.
[149]赵春江.金匮肾气丸与六味地黄丸异同[J].四川中医,2011,29(12): 118-119.
[150]陈涛.山茱萸水提液对骨质疏松模型小鼠骨形态学影响[J].天津药学,2003,15(4):5-6.
[151]杨茗,季晖,张树平,等.知母皂苷元对成骨细胞活性和破骨细胞分化及功能的影响[J].中国药物大学学报,2009,40(6)：544-546.
[152]Nian H, Qin L, Chen W, et al. Protective effect of steroidal saponins from rhizome of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats[J]. Acta Pharmacol Sinica,2006,27(6):728.
[153]Qin L, Han T, Zhang Q, et al. Antiosteoporotic chemical constituents from Er-Xian Decoction, a tr- aditional Chinese herbal formula [J]. J Ethnopharmacol,2008,118(2): 271.
[154]丁茜,张凤秋.淫羊藿苷对人牙周膜细胞表达核因子kB受体激活蛋白配体和护骨因子的影响[L].中华口腔医学杂志,2013,48(2)：68-71.
[155]高峰,莫新民,李劲平.淫羊藿苷治疗去势大鼠骨质疏松症基因表达谱分析[J].中国中医药信息杂志,2013,20(2)：43-45.
[156]吕明波,刘兴炎,葛宝丰,等.淫羊藿苷对破骨细胞活性的影响[J].中国骨伤,2007,20(8)：529-531.
[157]杨肖红,张昆.淫羊藿对糖尿病骨质疏松患者骨保护素水平的影响[J].山东医药,2010,50(49)：66-67.
[158]郭海玲,赵咏芳,王翔,等.淫羊藿苷对人成骨细胞增殖及OPG蛋白表达的实验研究[J].中国骨伤,2011,24(7)：585-588.
[159]杨荣平,寿清耀,涂永勤,等.补骨脂提取物对体外培养新生大鼠颅骨成骨细胞的影响[J].中药新药与临床药理,2007,18(1)：32-34.
[160]眭承志.骨碎补总黄酮治疗骨质疏松症作用机理实验研究进[J].中华中医药学刊,2010,28(6):1272-1274.
© 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 |