壮骨胶囊治疗原发性骨质疏松症的临床研究
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摘要
目的：
本课题拟通过中医证候疗效评价、骨密度(BMD)比较、雌二醇(E2)、睾酮(T)、骨钙素(BGP)、血清碱性磷酸酶(ALP)、羟脯氨酸(HYP)、尿钙(U-Ca)、血清抗酒石酸酸性磷酸酶(TRAP)、甲状旁腺激素(PTH)、降钙素(CT)、血钙(S-Ca)及血磷(S-P)等指标的变化来观察壮骨胶囊治疗原发性骨质疏松症(POP)的临床疗效,进一步探讨POP的发病机理及补肝肾、强筋骨、健脾益气、活血化瘀防治POP的初步作用机制,对减轻患者痛苦,提高临床疗效及临床推广提供了思路。
方法：
1.随机、双盲、平行对照的实验方法：
所有合格受试者均来自湖北省襄阳市中医医院骨科门诊及住院部患者,共80例,随机、双盲分为治疗组(壮骨胶囊组)和对照组(西药乐力胶囊组),每组40例。
2.实验用药：
对照组选用乐力胶囊；治疗组选用壮骨胶囊,两种胶囊由制剂室统一包装外形,标为壮骨Ⅰ号,并编号。按照患者编号及相对应的药物编号给药：每次6粒,每日3次,餐后半小时服用,1个月为一个疗程,、治疗6个疗程后统计疗效。
3.观察指标：
治疗前对两组性别、年龄、病程、证型、基础疾病、临床积分等基础资料进行了比较,经统计学分析无显著性差异(P>0.05),说明两组具有可比性。治疗后根据中医证候疗效评价、骨密度(BMD)比较、雌二醇(E2)、睾酮(T)、骨钙素(BGP)、血清碱性磷酸酶(ALP)、羟脯氨酸(HYP)、尿钙(U-Ca)、血清抗酒石酸酸性磷酸酶(TRAP)、甲状旁腺激素(PTH)、降钙素(CT)、血钙(S-Ca)及血磷(S-P)等指标的变化来进行统计学分析,评价出药物的有效性。
4.统计分析：
实验结束后进行统计分析,采用spss13.0统计分析软件进行。等级资料用Ridit检验,计量资料数据均以x±s表示,显著性检验采用t检验,计数资料采用u检验及x2检验。P<0.05将被认为所检验的差别有统计学意义。
结果：
1.综合疗效比较：治疗组显效12例,有效26例,无效2例,总有效率95%；对照组显效7例,有效25例,无效8例,总有效率80%,经Ridit检验,P<0.05,说明两组临床综合疗效有显著性差异。
2.中医证候疗效比较：两组药物对原发型骨质疏松症患者中医证候的总有效率比较,有统计学意义(P<0.05),提示治疗组对中医证候的改善优于对照组。
3.对骨密度的影响：治疗组治疗后BMD较治疗前有所改善,有统计学意义(P<0.05)；对照组治疗前后BMD得到改善,也有显著性差异(P<0.05)；但治疗组BMD的增加明显优于对照组,两组对比后治疗组BMD有统计学意义(P<0.05)。此结论表明治疗组中补肝肾、强筋骨、健脾益气、活血化瘀的中药成分有增加BMD,防止骨量流失的作用。
4.对骨形成的影响：两组治疗后ALP、BGP得到明显改善,与治疗前比较有显著性差异(P<0.01)；对照组治疗后ALP、BGP得到改善,有统计学意义(P<0.05)。两组比较,治疗后治疗组在骨形成的改善方面优于对照组(P<0.05),说明治疗组有促进骨形成的作用。
5.对骨吸收的影响：两组治疗后U-Hyp/Cr、U-Ca/Cr、TRAP均明显下降,与治疗前比较有显著性差异(P<0.05)两组比较,治疗后治疗组在骨形成的改善方面优于对照组(P<0.05),说明治疗组有抑制骨吸收的作用。
6.对钙代谢的影响：两组治疗后CT、S-Ca均明显改善(P<0.05)。两组间比较,治疗组在增加肠钙吸收,提高血钙浓度方面优于对照组改善方面优于对照组(P<0.05)；两组治疗后PTH均明显下降,与治疗前比较有显著性差异(P<0.05)。两组比较,治疗组防止骨钙溶出方面优于对照组(P<0.05)；两组治疗后S-P无明显变化(P>0.05)说明两组对磷的代谢无明显影响。
7.对性激素的影响：治疗组治疗后E2、T较治疗前有所改善,有统计学意义(P<0.05)；对照组治疗前后E2、T无明显改善(P<0.05)；表明壮骨胶囊具有类性激素作用。
8.对安全指标的影响：两组患者血、尿、粪常规、肝肾功能、心电图均无明显异常。
结论：
研究表明,壮骨胶囊治疗POP治法是补肾壮骨、活血化瘀法,能明显改善中医证候、增加骨密度等指标,且临床使用安全无毒副作用,值得推广使用。
Objectives
This topic proposed by syndromes bone mineral density (BMD) effect assessment, compared, estradiol (E2), testosterone(T),osteocalcin (BGP), serum alkaline phosphatase (ALP), hydroxyproline (HYP), urinary calcium (U-Ca), plasma fight tartaric acid salt acidic phosphatase (TRAP), parathyroid hormone (PTH), of calcitonin (CT), blood calcium (S-Ca) and phosphate (S-P) index variation to observe bones capsule the treatment of primary osteoporosis (POP), and further explore the clinical curative effect of the pathogenesis and POP for strong bones and muscles, hepatorenal, spleen yiqi, promoting blood circulation to remove blood stasis control mechanism, the preliminary POP to relieve pain and improve clinical efficacy and clinical promotion offered the thought.
Methods
1. Randomized, double-blind, parallel comparison experimental methods:
All qualified participants are fromhubei xiangyang city outpatient department and the inpatient orthopaedic hospital of traditional, were 80 cases of patients, randomized, double-blind, divided into the treatment group (bones capsule group) and the control group (western medicine le force capsule group),40 cases in each group.
2. Experimental drugs:
The control group choose joy force capsule; The treatment group selection, two capsules bones capsule pharmaceutical preparation, unified packaging appearance by marking for bones, and Numbers. No.ⅠAccording to Numbers and corresponding with drug dosing:every time six Numbers to grain,3 times a day, eat hind half an hour take, 1 months for a period of treatment, after treated for 6 cycles statistical curative effect.
3. Outcome measures:
Before treatment with two groups of gender, age, duration, syndrome type, basic diseases, clinical integral and other basic material were compared by statistical analysis, no significant difference (P>0.05), explain two groups of comparable. After the treatment effect assessment according to syndromes bone mineral density (BMD), comparative, estradiol (E2), testosterone (T), osteocalcin (BGP), serum alkaline phosphatase (ALP), hydroxyproline (HYP), urinary calcium (U-Ca), plasma fight tartaric acid salt acidic phosphatase (TRAP), parathyroid hormone (PTH), of calcitonin (CT), blood calcium (S-Ca) and phosphate (S-P) index variation to assess the statistical analysis of the drug's effectiveness evaluation.
4. Statistical analysis:
After the end of experiment statistical analysis, using statistical analysis software spssl3.0. Level Ridit inspection, measuring data use data are in s said significant test using t-test, counting material adopt u inspection and x2 inspection. P<0.05 will be considered by the testing of a statistically significant difference.
Results
1. The total curative effect comparison:treatment group powerfully in 12 cases, effective 26 cases, invalid 2 cases failure; the total effective 95%; The control group,10 cases were effective got 27 cases, invalid 3 cases failure; the total effective Ridit inspection, the joys, P>0.01, explain two groups of clinical comprehensive effect no significant differences.
2. Compare syndromes curative effect of two groups drugs original hairstyle osteoporosis patients total effective syndromes are statistically significant comparative, (P<0.05), indicating that the treatment group to improve syndromes than control group.
3. The effect on bone mineral density BMD after treatment:treatment group than before treatment improved, a statistically significant (P<0.05). The control group BMD improved after treatment, also have significant difference (P<0.05). But the increase of treatment group was better than control BMD, two groups in treatment group contrast BMD after a statistically significant (P<0.05). The conclusion shows that the treatment group for strong bones and muscles in the kidney, and enriching qi, promoting blood circulation to remove blood stasis of traditional Chinese medicine composition have increased BMD, prevent bone loss function.
4. The influence of bone formation, the two groups after treating ALP, improved obviously BGP before treatment, and with significant difference (P<0.01); The control group after treatment improved BGP, ALP was statistically significant (P<0.05). Two groups of comparisons, the treatment group in the improvement of bone formation than in control group (P<0.05), indicating that the treatment group have promote bone formation action.
5. The influence of bone resorption, two groups after treating U-Hyp/Cr, U-Ca/Cr, TRAP, and were significantly drop before treatment with significant difference (P<0.05) two groups of comparisons, the treatment group in the improvement of bone formation than in control group (P<0.05), indicating that the treatment group have inhibit bone absorption effect.
6. The effect of calcium metabolism:two groups after treating CT, S-Ca were markedly improved (P<0.05). Comparison between the two groups in treatment group increased calcium uptake, improve bowel blood calcium concentration improved better than control group in better than control group (P<0.05). Both groups were obviously decreased after treatment with PTH before treatment, with significant difference (P<0.05). Two groups of comparisons, the treatment group prevent bone calcium dissloution better than the control group (P<0.05). The two groups after treating S-P (P> 0.05) not significantly affect the metabolism of phosphorus.
7. The influence of sex hormones two groups after treatment were more treatment,T, E2 improved before, but this was not statistically significant (P>0.05).
8. The influence of safety index:two groups of patients blood and urine and kidney function, conventional, dung electrocardiogram (ecg) were not significantly abnormal.
Conclusion
Research shows that bones capsule for POP alopecia kidney bones, is to remove stasis, can significantly improve syndromes, increase in bone density, and clinical use indices such as non-toxic side effects, is worth popularizing.
本课题拟通过中医证候疗效评价、骨密度(BMD)比较、雌二醇(E2)、睾酮(T)、骨钙素(BGP)、血清碱性磷酸酶(ALP)、羟脯氨酸(HYP)、尿钙(U-Ca)、血清抗酒石酸酸性磷酸酶(TRAP)、甲状旁腺激素(PTH)、降钙素(CT)、血钙(S-Ca)及血磷(S-P)等指标的变化来观察壮骨胶囊治疗原发性骨质疏松症(POP)的临床疗效,进一步探讨POP的发病机理及补肝肾、强筋骨、健脾益气、活血化瘀防治POP的初步作用机制,对减轻患者痛苦,提高临床疗效及临床推广提供了思路。
方法：
1.随机、双盲、平行对照的实验方法：
所有合格受试者均来自湖北省襄阳市中医医院骨科门诊及住院部患者,共80例,随机、双盲分为治疗组(壮骨胶囊组)和对照组(西药乐力胶囊组),每组40例。
2.实验用药：
对照组选用乐力胶囊；治疗组选用壮骨胶囊,两种胶囊由制剂室统一包装外形,标为壮骨Ⅰ号,并编号。按照患者编号及相对应的药物编号给药：每次6粒,每日3次,餐后半小时服用,1个月为一个疗程,、治疗6个疗程后统计疗效。
3.观察指标：
治疗前对两组性别、年龄、病程、证型、基础疾病、临床积分等基础资料进行了比较,经统计学分析无显著性差异(P>0.05),说明两组具有可比性。治疗后根据中医证候疗效评价、骨密度(BMD)比较、雌二醇(E2)、睾酮(T)、骨钙素(BGP)、血清碱性磷酸酶(ALP)、羟脯氨酸(HYP)、尿钙(U-Ca)、血清抗酒石酸酸性磷酸酶(TRAP)、甲状旁腺激素(PTH)、降钙素(CT)、血钙(S-Ca)及血磷(S-P)等指标的变化来进行统计学分析,评价出药物的有效性。
4.统计分析：
实验结束后进行统计分析,采用spss13.0统计分析软件进行。等级资料用Ridit检验,计量资料数据均以x±s表示,显著性检验采用t检验,计数资料采用u检验及x2检验。P<0.05将被认为所检验的差别有统计学意义。
结果：
1.综合疗效比较：治疗组显效12例,有效26例,无效2例,总有效率95%；对照组显效7例,有效25例,无效8例,总有效率80%,经Ridit检验,P<0.05,说明两组临床综合疗效有显著性差异。
2.中医证候疗效比较：两组药物对原发型骨质疏松症患者中医证候的总有效率比较,有统计学意义(P<0.05),提示治疗组对中医证候的改善优于对照组。
3.对骨密度的影响：治疗组治疗后BMD较治疗前有所改善,有统计学意义(P<0.05)；对照组治疗前后BMD得到改善,也有显著性差异(P<0.05)；但治疗组BMD的增加明显优于对照组,两组对比后治疗组BMD有统计学意义(P<0.05)。此结论表明治疗组中补肝肾、强筋骨、健脾益气、活血化瘀的中药成分有增加BMD,防止骨量流失的作用。
4.对骨形成的影响：两组治疗后ALP、BGP得到明显改善,与治疗前比较有显著性差异(P<0.01)；对照组治疗后ALP、BGP得到改善,有统计学意义(P<0.05)。两组比较,治疗后治疗组在骨形成的改善方面优于对照组(P<0.05),说明治疗组有促进骨形成的作用。
5.对骨吸收的影响：两组治疗后U-Hyp/Cr、U-Ca/Cr、TRAP均明显下降,与治疗前比较有显著性差异(P<0.05)两组比较,治疗后治疗组在骨形成的改善方面优于对照组(P<0.05),说明治疗组有抑制骨吸收的作用。
6.对钙代谢的影响：两组治疗后CT、S-Ca均明显改善(P<0.05)。两组间比较,治疗组在增加肠钙吸收,提高血钙浓度方面优于对照组改善方面优于对照组(P<0.05)；两组治疗后PTH均明显下降,与治疗前比较有显著性差异(P<0.05)。两组比较,治疗组防止骨钙溶出方面优于对照组(P<0.05)；两组治疗后S-P无明显变化(P>0.05)说明两组对磷的代谢无明显影响。
7.对性激素的影响：治疗组治疗后E2、T较治疗前有所改善,有统计学意义(P<0.05)；对照组治疗前后E2、T无明显改善(P<0.05)；表明壮骨胶囊具有类性激素作用。
8.对安全指标的影响：两组患者血、尿、粪常规、肝肾功能、心电图均无明显异常。
结论：
研究表明,壮骨胶囊治疗POP治法是补肾壮骨、活血化瘀法,能明显改善中医证候、增加骨密度等指标,且临床使用安全无毒副作用,值得推广使用。
Objectives
This topic proposed by syndromes bone mineral density (BMD) effect assessment, compared, estradiol (E2), testosterone(T),osteocalcin (BGP), serum alkaline phosphatase (ALP), hydroxyproline (HYP), urinary calcium (U-Ca), plasma fight tartaric acid salt acidic phosphatase (TRAP), parathyroid hormone (PTH), of calcitonin (CT), blood calcium (S-Ca) and phosphate (S-P) index variation to observe bones capsule the treatment of primary osteoporosis (POP), and further explore the clinical curative effect of the pathogenesis and POP for strong bones and muscles, hepatorenal, spleen yiqi, promoting blood circulation to remove blood stasis control mechanism, the preliminary POP to relieve pain and improve clinical efficacy and clinical promotion offered the thought.
Methods
1. Randomized, double-blind, parallel comparison experimental methods:
All qualified participants are fromhubei xiangyang city outpatient department and the inpatient orthopaedic hospital of traditional, were 80 cases of patients, randomized, double-blind, divided into the treatment group (bones capsule group) and the control group (western medicine le force capsule group),40 cases in each group.
2. Experimental drugs:
The control group choose joy force capsule; The treatment group selection, two capsules bones capsule pharmaceutical preparation, unified packaging appearance by marking for bones, and Numbers. No.ⅠAccording to Numbers and corresponding with drug dosing:every time six Numbers to grain,3 times a day, eat hind half an hour take, 1 months for a period of treatment, after treated for 6 cycles statistical curative effect.
3. Outcome measures:
Before treatment with two groups of gender, age, duration, syndrome type, basic diseases, clinical integral and other basic material were compared by statistical analysis, no significant difference (P>0.05), explain two groups of comparable. After the treatment effect assessment according to syndromes bone mineral density (BMD), comparative, estradiol (E2), testosterone (T), osteocalcin (BGP), serum alkaline phosphatase (ALP), hydroxyproline (HYP), urinary calcium (U-Ca), plasma fight tartaric acid salt acidic phosphatase (TRAP), parathyroid hormone (PTH), of calcitonin (CT), blood calcium (S-Ca) and phosphate (S-P) index variation to assess the statistical analysis of the drug's effectiveness evaluation.
4. Statistical analysis:
After the end of experiment statistical analysis, using statistical analysis software spssl3.0. Level Ridit inspection, measuring data use data are in s said significant test using t-test, counting material adopt u inspection and x2 inspection. P<0.05 will be considered by the testing of a statistically significant difference.
Results
1. The total curative effect comparison:treatment group powerfully in 12 cases, effective 26 cases, invalid 2 cases failure; the total effective 95%; The control group,10 cases were effective got 27 cases, invalid 3 cases failure; the total effective Ridit inspection, the joys, P>0.01, explain two groups of clinical comprehensive effect no significant differences.
2. Compare syndromes curative effect of two groups drugs original hairstyle osteoporosis patients total effective syndromes are statistically significant comparative, (P<0.05), indicating that the treatment group to improve syndromes than control group.
3. The effect on bone mineral density BMD after treatment:treatment group than before treatment improved, a statistically significant (P<0.05). The control group BMD improved after treatment, also have significant difference (P<0.05). But the increase of treatment group was better than control BMD, two groups in treatment group contrast BMD after a statistically significant (P<0.05). The conclusion shows that the treatment group for strong bones and muscles in the kidney, and enriching qi, promoting blood circulation to remove blood stasis of traditional Chinese medicine composition have increased BMD, prevent bone loss function.
4. The influence of bone formation, the two groups after treating ALP, improved obviously BGP before treatment, and with significant difference (P<0.01); The control group after treatment improved BGP, ALP was statistically significant (P<0.05). Two groups of comparisons, the treatment group in the improvement of bone formation than in control group (P<0.05), indicating that the treatment group have promote bone formation action.
5. The influence of bone resorption, two groups after treating U-Hyp/Cr, U-Ca/Cr, TRAP, and were significantly drop before treatment with significant difference (P<0.05) two groups of comparisons, the treatment group in the improvement of bone formation than in control group (P<0.05), indicating that the treatment group have inhibit bone absorption effect.
6. The effect of calcium metabolism:two groups after treating CT, S-Ca were markedly improved (P<0.05). Comparison between the two groups in treatment group increased calcium uptake, improve bowel blood calcium concentration improved better than control group in better than control group (P<0.05). Both groups were obviously decreased after treatment with PTH before treatment, with significant difference (P<0.05). Two groups of comparisons, the treatment group prevent bone calcium dissloution better than the control group (P<0.05). The two groups after treating S-P (P> 0.05) not significantly affect the metabolism of phosphorus.
7. The influence of sex hormones two groups after treatment were more treatment,T, E2 improved before, but this was not statistically significant (P>0.05).
8. The influence of safety index:two groups of patients blood and urine and kidney function, conventional, dung electrocardiogram (ecg) were not significantly abnormal.
Conclusion
Research shows that bones capsule for POP alopecia kidney bones, is to remove stasis, can significantly improve syndromes, increase in bone density, and clinical use indices such as non-toxic side effects, is worth popularizing.
引文
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[40]翁维良,王怡,马惠敏等.20种活血药对血液黏滞性作用的比较观察[J].中医杂志,1984,(2)：69.
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[1]王和鸣,汪宝军,王竹风,等.福建省中老年人骨密度的流行病学调查.中国骨质疏松杂志,2004,10(4)：535-537.
[2]National osteoporosis foundation. Osteoporosis:review of the evidence for prevention, diagnosis and treatment and cost-effectiveness analysis. Introduction. Osteopoosis International.1998,(Suppl):79-80.
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[11]曾炎辉,张泽攻,林水城,等.绝经后骨质疏松症患肯骨代谢生化指标检测及淫羊藿作用初探[J].国际医药卫生导报,2005,11(6)：24.
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[14]朱太咏,石印玉,张戈,等.补肾益精方提高卵巢切除大鼠骨质疏松模型松质骨骨质量的实验研究.中国中西医结合杂志.2001,21(9)：688-692.
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[13]刘卞生,张思雄.实用临床老年学[M].北京：中国医药出版社, 2001：533.
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[15]周琦,周建烈.最新“美国防治骨质疏松症医师指南”解读[J].中国骨质疏松杂志,2008,14(5)：23-25.
[16]蒋位庄,王和鸣.中医骨病学[M].北京：人民卫生出版社2002,294-301.
[17]Schalrer C, Iaxbin J, Troisi R,et al. Menopausal estrogen and estrogen-pmges-tin replacement therapy and breast cancer risk. J AMA.2000.283:485-491.
[18]刘英,陈冉红.鲑鱼降钙素致腹部绞痛与心律失92例.药物不良反应杂志[J].2007,9：282
[19]张红莲,王雅楠,王建华.补骨脂的化学成分及药理活性研究概况[J]天然产物研究与开发,2010,22(5)：317-318
[20]Niu JZet 02. Phytoestrogenic activity of five kinds of Chinese herbal medicines including fructus psoraleae. J Beijing Univ Tradit Chin Med,2008.31:676-681.
[21]Shou QY, et 01. Study on the effective constituents Research & Clin Pharm,2007,18:425-327.
[22]Xiong Z, Wang D, Xu Y, et al. Osteoblastic differentiation bioessay and its application to investigating the activity of fractions and colmpounds from Psoralea corylifolia L. Phannazie,2003,58(12):925.
[23]张润荃,史凤芹,庞淑珍,等.补骨脂对分离破骨细胞作用的研究.现代口腔医学杂志,1995,9(3)：136.
[24]程志安,吴燕峰,黄智清,等.续断对成骨细胞增殖分化、凋亡和细胞周期的影响[J].中医正骨,2004,16(12)：1-3.
[25]纪顺心,吴雪琴,李崇芳.中药续断对大鼠实验性骨损伤愈合作用的观察[J].中草药,1997,28(2)：98—99.
[26]Oh KO, Kim SW, Kim JY, et al. Efkct () f Rehmannia glutinosa Libosch extracts on bone metaboIism[J].Clin Chim Acta.2003,334:185-95.
[27]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.
[28]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(原中国医药学报),2005,20(3)：161-162.
[29]Sun J S, Chun YL, Dong GC, et al. The effect of Gu Sui Bu(Ⅰ)on bonecell activities. Biomaterials,2002,23(16):3377-3385.
[30]蔡春水,肖平,张毅等.骨碎补总黄酮对巨噬细胞分泌细胞因子TNF-α、IL-6水平的影响[J].中国矫形外科杂志,2006,14(15)：1185-1187.
[31]全宏勋.黄芪抗辐射作用的临床研究[J].中草药,1993,24(8)：423.
[32]李朝阳,吴铁,黄连芳,等.黄芪水提液与已烯雌酚对去卵巢大鼠骨代谢的影响[J].中草药,1998,29(1)：27.
[33]毛万芳,刘远旭,王富.抗衰老中药刺五加作用之探源[J].中外健康文摘.2010,7(27)：73-75.
[34]Usui T. Ikeda Y. Tagami T, et al. The phytodaemieal lindleyin,isolated from the Rhei rhizome,mediates honmnal effects through estrogen receptors. J Endocrinal,2002, 175(2):288.
[35]史凤芹,于世凤,张润荃等.大黄对破骨细胞性骨吸收作用的研究[J].现代口腔医学杂志,1995,9(4)：193.
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[38]顾云,孟娟茹.介绍一种简易的抗血栓药物体内筛选法[J].中国药理学通报,1991,7(4)：317.
[39]冈本彰佑.数种生药对纤维溶酶系的作用及其解析[J].国外医药.中医中药分册,1984(1)：54.
[40]翁维良,王怡,马惠敏等.20种活血药对血液黏滞性作用的比较观察[J].中医杂志,1984,(2)：69.
[41]李隆敏,周樱,邵幸署等.丹参酮防治绝经后骨质疏松[J].中国骨质疏松杂志.1996,2(1)78.
[42]崔燎,邹宜,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松所致大鼠付质疏松[J].中国药理学通报,2004,20(3)：286
[43]郑高利,张信岳.葛根异黄酮刘去卵巢大鼠骨矿密度和骨密度的影响[J].中草药,2001,32(5)：4 22.
[44]杨卫红,周建烈.补充钙和维生素D预防骨质疏松性骨折疗效述评[J].中国骨质疏松杂志,2008,14(11)：797-826.
[45]赵治友,邬亚军.骨质疏松症的中医辨证思路与治法研究[J].浙江中医药大学学报,2007,3(275)：2.
[46]刘和娣, 李思, 刘昆, 等. 补肾中药对骨质疏松大鼠CaBP-D9K基因及表达的影响[J].中国骨质疏松杂志,1996,2(3)：62.
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