Effects of Puerarin on Bone Density in Rats and Mice: A Meta-analysis

doi:10.12300/j.issn.1674-5817.2023.127

Abstract

Abstract:

Objective To evaluate the effects of puerarin on bone density in rats and mice through a meta-analysis. Methods The databases, including CNKI, SinoMed, Wanfang data, VIP, PubMed, EMBase, Web of Science, the Cochrane Library, and Scopus from their inception to November 6, 2023, were searched for literature on the effects of puerarin treatment on bone density in rats and mice. Inclusion criteria for the literature were randomized controlled trials with a placebo or blank control group; the subject animals were rats or mice; the intervention was puerarin; and the results included bone density measurements. Exclusion criteria included combination therapy with puerarin; lack of original research data; unpublished studies; and using mandible as the measurement site for bone density. Risks of bias were assessed using SYRCLE's RoB tool. Data analysis was conducted with Stata 16.0 and Rev Man 5.3 software. Results After applying the inclusion and exclusion criteria, a total of 429 records were identified and 42 articles covering 41 studies were ultimately included. 925 animals were involved and the data analysis results indicated that puerarin improved bone density in rats and mice compared to the control group: femur [37 studies, n=824, standardized mean difference （SMD)=2.12, 95% confidence interval (CI)=1.69-2.54, P < 0.000 1], lumbar spine (13 studies, n=271, SMD=2.25, 95% CI=1.49-3.01, P < 0.000 1), tibia (4 studies, n=95, SMD=0.94, 95% CI=0.05-1.83, P=0.04), and the whole body (4 studies, n=94, SMD=1.89, 95% CI=0.50-3.29, P=0.008), with all inter-group differences in bone density being statistically significant. Conclusion Puerarin can improve bone density in rats and mice. This study provides a valuable reference for clinical studies on the prevention and treatment of osteoporosis with puerarin.

Key words: Puerarin, Bone density, Meta-analysis, Rats, Mice

CLC Number:

Q95-22

Jinhua HU, Jingjie HAN, Min JIN, Bin HU, Yuefen LOU. Effects of Puerarin on Bone Density in Rats and Mice: A Meta-analysis[J]. Laboratory Animal and Comparative Medicine, 2024, 44(2): 149-161.

Figures/Tables 8

References 60

1	李斌斌, 于世凤. 葛根素调控骨代谢的体外实验研究[J]. 北京大学学报(医学版), 2003, 35(1):74-77. DOI: 10.19723/j.issn.1671-167x.2003.01.022 .
	LI B B, YU S F. Effect of puerarin on the bone metabolism in vitro [J]. J Beijing Med Univ, 2003, 35(1):74-77. DOI: 10.19723/j.issn.1671-167x.2003.01.022 .
2	TIYASATKULKOVIT W, CHAROENPHANDHU N, WONGDEE K, et al. Upregulation of osteoblastic differentiation marker mRNA expression in osteoblast-like UMR106 cells by puerarin and phytoestrogens from Pueraria mirifica [J]. Phytomedicine, 2012, 19(13):1147-1155. DOI: 10.1016/j.phymed.2012.07.010 .
3	SHAN Z M, CHENG N, HUANG R, et al. Puerarin promotes the proliferation and differentiation of MC3T3-E1 cells via microRNA-106b by targeting receptor activator of nuclear factor-κB ligand[J]. Exp Ther Med, 2018, 15(1):55-60. DOI: 10.3892/etm.2017.5405 .
4	TIYASATKULKOVIT W, MALAIVIJITNOND S, CHAROENPHANDHU N, et al. Pueraria mirifica extract and puerarin enhance proliferation and expression of alkaline phosphatase and type I collagen in primary baboon osteoblasts[J]. Phytomedicine, 2014, 21(12):1498-1503. DOI: 10.1016/j.phymed.2014.06.019 .
5	WANG N, WANG X L, CHENG W X, et al. Puerarin promotes osteogenesis and inhibits adipogenesis in vitro [J]. Chin Med, 2013, 8(1):17. DOI: 10.1186/1749-8546-8-17 .
6	LI H, CHEN B P, PANG G F, et al. Anti-osteoporotic activity of puerarin 6"-O-xyloside on ovariectomized mice and its potential mechanism[J]. Pharm Biol, 2016, 54(1):111-117. DOI: 10.3109/13880209.2015.1017885 .
7	LEE M R, KIM B, LEE Y J, et al. Ameliorative effects of Pueraria lobata extract on postmenopausal symptoms through promoting estrogenic activity and bone markers in ovariectomized rats[J]. Evid Based Complement Alternat Med, 2021, 2021:7924400. DOI: 10.1155/2021/7924400 .
8	ZHOU G N, AN Z P, ZHAO W J, et al. Sex differences in outcomes after stroke among patients with low total cholesterol levels: a large hospital-based prospective study[J]. Biol Sex Differ, 2016, 7:62. DOI: 10.1186/s13293-016-0109-3 .
9	GUO C J, XIE J J, HONG R H, et al. Puerarin alleviates streptozotocin (STZ)-induced osteoporosis in rats through suppressing inflammation and apoptosis via HDAC1/HDAC3 signaling[J]. Biomed Pharmacother, 2019, 115:108570. DOI: 10.1016/j.biopha.2019.01.031 .
10	KULCZYŃSKI B, GRAMZA-MICHAŁOWSKA A, SULIBURSKA J, et al. Puerarin—an isoflavone with beneficial effects on bone health[J]. Front Biosci (Landmark Ed), 2021, 26(12):1653-1667. DOI: 10.52586/5058 .
11	HOOIJMANS C R, ROVERS M M, DE VRIES R B M, et al. SYRCLE's risk of bias tool for animal studies[J]. BMC Med Res Methodol, 2014, 14:43. DOI: 10.1186/1471-2288-14-43 .
12	LI B, LIU M Y, WANG Y, et al. Puerarin improves the bone micro-environment to inhibit OVX-induced osteoporosis via modulating SCFAs released by the gut microbiota and repairing intestinal mucosal integrity[J]. Biomed Pharmacother, 2020, 132:110923. DOI: 10.1016/j.biopha. 2020.110923 .
13	LI B, WANG Y, GONG S Q, et al. Puerarin improves OVX-induced osteoporosis by regulating phospholipid metabolism and biosynthesis of unsaturated fatty acids based on serum metabolomics[J]. Phytomedicine, 2022, 102:154198. DOI: 10.1016/j.phymed.2022.154198 .
14	LI B B, LIU H, JIA S N. Puerarin enhances bone mass by promoting osteoblastogenesis and slightly lowering bone marrow adiposity in ovariectomized rats[J]. Biol Pharm Bull, 2014, 37(12):1919-1925. DOI: 10.1248/bpb.b14-00513 .
15	覃成禹, 周昊楠, 陈远明. 葛根素对绝经后骨质疏松大鼠不同部位骨骼的抗骨质疏松作用差异的研究[J]. 中华老年骨科与康复电子杂志, 2023, 9(1):23-27. DOI: 10.3877/cma.j.issn.2096-0263.2023.01.005 .
	QIN C Y, ZHOU H N, CHEN Y M. The difference of anti-osteoporosis effect of Puerarin on different parts of bone in postmenopausal osteoporosis rats[J]. Chin J Geriatr Orthop Rehabil Electron Ed, 2023, 9(1):23-27. DOI: 10.3877/cma.j.issn.2096-0263.2023.01.005 .
16	杨砥, 关智宇. 葛根素基于PPAR-γ/Axin2/Wnt信号通路对去卵巢骨质疏松大鼠的干预作用[J]. 中国老年学杂志, 2023, 43(13):3228-3232. DOI: 10.3969/j.issn.1005-9202.2023.13.041 .
	YANG D, GUAN Z Y. Intervention of puerarin on ovariectomized osteoporosis rats based on PPAR-γ/Axin2/wnt signal pathway[J]. Chin J Gerontol, 2023, 43(13):3228-3232. DOI: 10.3969/j.issn.1005-9202.2023.13.041 .
17	王国波, 罗波, 苟印尧, 等. 葛根素联合雌二醇对大鼠骨质疏松性骨折愈合的影响[J]. 中国临床药理学杂志, 2020, 36(14):2052-2055. DOI: 10.13699/j.cnki.1001-6821.2020.14.039 .
	WANG G B, LUO B, GOU Y R, et al. Effect of puerarin combined with estradiol on the healing of osteoporotic fracture in rats[J]. Chin J Clin Pharmacol, 2020, 36(14):2052-2055. DOI: 10.13699/j.cnki.1001-6821.2020.14.039 .
18	李海, 王金花, 黄海玲, 等. 葛根素联合雌二醇对去卵巢大鼠骨质疏松的治疗作用[J]. 中国老年学杂志, 2012, 32(18):3950-3952. DOI: 10.3969/j.issn.1005-9202.2012.18.039 .
	LI H, WANG J H, HUANG H L, et al. Effect of Puerarin combined estradiol on ovariectomized osteoporosis[J]. Chin J Gerontol, 2012, 32(18):3950-3952. DOI: 10.3969/j.issn.1005-9202.2012.18.039 .
19	梁恒, 邝志强, 王攀攀, 等. 葛根素通过BMP-2调节去卵巢大鼠骨代谢[J]. 广州医学院学报, 2012, 40(3):1-4.
	LIANG H, KUANG Z Q, WANG P P, et al. Puerarin regulates bone metabolism via bone morphogenic protein-2 in ovariectomized rats[J]. Acad J Guangzhou Med Coll, 2012, 40(3):1-4.
20	刘浩, 李斌斌. 葛根素预防雌激素缺乏性骨质疏松的机制探讨[J]. 中国比较医学杂志, 2012, 22(6):16-20. DOI: 10.3969/j.issn.1671-7856.2012.06.005 .
	LIU H, LI B B. Effect of puerarin on the osteoporosis resulted from ovariectomy in rats[J]. Chin J Comp Med, 2012, 22(6):16-20. DOI: 10.3969/j.issn.1671-7856.2012.06.005 .
21	黄海玲, 李海, 王金花, 等. 雌激素与不同剂量的葛根素联合对去卵巢大鼠骨质疏松的影响[J]. 中国妇幼保健, 2011, 26(33):5228-5231.
	HUANG H L, LI H, WANG J H, et al. Effect of estradiol combined with different doses of puerarin on osteoporosis of ovariectomized rats[J]. Matern Child Health Care China, 2011, 26(33):5228-5231.
22	葸慧荣, 李文苑, 杨芳芳, 等. 中药葛根素对青年大鼠峰值骨量的影响研究[J]. 中国骨质疏松杂志, 2018, 24(4):514-519. DOI: 10.3969/j.issn.1006-7108.2018.04.019 .
	XI H R, LI W Y, YANG F F, et al. Effect of Puerarin on peak bone mass in young rats[J]. Chin J Osteoporos, 2018, 24(4):514-519. DOI: 10.3969/j.issn.1006-7108.2018.04.019 .
23	葸慧荣, 杨芳芳, 高玉海, 等. 葛根素和白藜芦醇对青年大鼠峰值骨量的影响研究[J]. 中国骨伤, 2018, 31(7):635-641. DOI: 10.3969/j.issn.1003-0034.2018.07.010 .
	XI H R, YANG F F, GAO Y H, et al. Resveratrol and puerarin on peak bone mass in young rats[J]. China J Orthop Traumatol, 2018, 31(7):635-641. DOI: 10.3969/j.issn.1003-0034.2018.07.010 .
24	岳海振, 蔡军, 马新强, 等. 葛根素对绝经后骨质疏松大鼠骨代谢、骨密度及骨生物力学的影响[J]. 中国骨质疏松杂志, 2021, 27(1):77-81. DOI: 10.3969/j.issn.1006-7108.2021.01.017 .
	YUE H Z, CAI J, MA X Q, et al. Effect of puerarin on bone metabolism, bone mineral density, and bone biomechanics in postmenopausal osteoporosis rats[J]. Chin J Osteoporos, 2021, 27(1):77-81. DOI: 10.3969/j.issn.1006-7108.2021.01.017 .
25	李凯, 秦荣, 邵佳乐, 等. 葛根素对废用性骨质疏松大鼠模型的防治作用及机制研究[J]. 中国中药杂志, 2019, 44(3):535-540. DOI: 10.19540/j.cnki.cjcmm.20181012.003 .
	LI K, QIN R, SHAO J L, et al. Preventive effect and mechanism of puerarin on rat models of disuse osteoporosis[J]. China J Chin Mater Med, 2019, 44(3):535-540. DOI: 10.19540/j.cnki.cjcmm.20181012.003 .
26	李凯, 高玉海, 王玺, 等. 葛根素对尾吊大鼠发生废用性骨质疏松的防治作用[J]. 中华骨质疏松和骨矿盐疾病杂志, 2019, 12(1):50-57. DOI: 10.3969/j.issn.1674-2591.2019.01.007 .
	LI K, GAO Y H, WANG X, et al. Effects of puerarin on prevention of disuse osteoporosis in hindlimb suspension rats[J]. Chin J Osteoporos Bone Miner Res, 2019, 12(1):50-57. DOI: 10.3969/j.issn.1674-2591.2019.01.007 .
27	肖兰, 李靖. 有氧运动配合葛根素对去卵巢大鼠骨密度、血清细胞因子和骨代谢相关生化指标的影响[J]. 西安体育学院学报, 2009, 26(5):575-579, 601. DOI: 10.3969/j.issn.1001-747X.2009.05.017 .
	XIAO L, LI J. Effect of exercise training and puerarin on bone mineral density, cytokine, bone metabolism index in ovariectomized rats[J]. J Xi'an Phys Educ Univ, 2009, 26(5):575-579, 601. DOI: 10.3969/j.issn.1001-747X.2009.05.017 .
28	XIAO L, ZHONG M D, HUANG Y, et al. Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways[J]. Aging, 2020, 12(21):21706-21729. DOI: 10.18632/aging.103976 .
29	吕立桃, 范卫闯, 白登彦, 等. 葛根素对糖尿病性骨质疏松小鼠骨密度及氧化应激的影响[J]. 新中医, 2022, 54(21):7-12. DOI: 10.13457/j.cnki.jncm.2022.21.002 .
	LYU L T, FAN W C, BAI D Y, et al. Effect of puerarin on bone mineral density and oxidative stress in mice with diabetic osteoporosis[J]. N Chin Med, 2022, 54(21):7-12. DOI: 10.13457/j.cnki.jncm.2022.21.002 .
30	吕立桃, 范卫闯. 葛根素对去卵巢大鼠骨代谢平衡的影响[J]. 西部中医药, 2023, 36(7):27-30. DOI: 10.12174/j.issn.2096-9600.2023.07.06 .
	LYU L T, FAN W C. Influence of puerarin on bone metabolic equilibrium in ovariectomized rats[J]. West J Tradit Chin Med, 2023, 36(7):27-30. DOI: 10.12174/j.issn.2096-9600.2023.07.06 .
31	WANG P P, ZHU X F, YANG L, et al. Puerarin stimulates osteoblasts differentiation and bone formation through estrogen receptor, p38 MAPK, and Wnt/β-catenin pathways[J]. J Asian Nat Prod Res, 2012, 14(9):897-905. DOI: 10.1080/10286020.2012.702757 .
32	田泉, 汤旭磊, 白孟海, 等. 葛根素对去卵巢大鼠骨质疏松和血脂的作用[J]. 中华老年医学杂志, 2006, 25(7):543-545. DOI: 10.3760/j: issn: 0254-9026.2006.07.023 .
	TIAN Q, TANG X L, BAI M H, et al. Effects of puerarin on osteoporosis and blood lipids in ovariectomized rats[J]. Chin J Geriatr, 2006, 25(7):543-545. DOI: 10.3760/j: issn: 0254-9026.2006.07.023 .
33	周强, 付庭斌. 葛根素对去卵巢大鼠骨质疏松性骨折愈合的促进作用[J]. 中国临床康复, 2006, 10(27):45-47.
	ZHOU Q, FU T B. Effect of puerarin on the healing of osteoporotic fracture in ovariectomized rats[J]. Chin J Clin Rehabil, 2006, 10(27):45-47.
34	遇实, 季庆辉, 王婧, 等. 葛根素联合雌激素对PMOP大鼠治疗作用及机制实验研究[J]. 黑龙江医药科学, 2019, 42(4):213-215, 217.
	YU S, JI Q H, WANG J, et al. Experimental study on therapeutic effect and mechanism of puerarin combined with estrogen on PMOP rats[J]. Heilongjiang Med Pharm, 2019, 42(4):213-215, 217.
35	周胜虎, 刘兴炎, 王湘辉, 等. 葛根素对卵巢切除大鼠血清E2、腰椎BMD及骨髓细胞IL-6 mRNA表达的影响[J]. 中国骨质疏松杂志, 2010, 16(12):946-948. DOI: 10.3969/j.issn.1006-7108.2010.12.011 .
	ZHOU S H, LIU X Y, WANG X H, et al. Effects of puerarin on the level of serum E2, bone mineral density of the lumbar vertebrae, and the mRNA expression of interleukin 6 in ovariectomized rats[J]. Chin J Osteoporos, 2010, 16(12):946-948. DOI: 10.3969/j.issn.1006-7108.2010.12.011 .
36	曾锁林, 施熊兵. 葛根素对去势雌性大鼠骨质疏松症及PI3 KAKT信号转导通路的影响[J]. 河北医药, 2018, 40(23):3566-3569. DOI: 10.3969/j.issn.1002-7386.2018.23.010 .
	ZENG S L, SHI X B. Effects of puerarin on osteoporosis and PI3K/AKT signaling pathway in ovariectomized female rats[J]. Hebei Med J, 2018, 40(23):3566-3569. DOI: 10.3969/j.issn.1002-7386.2018.23.010 .
37	曾锁林, 施能兵, 刘异. 葛根素对激素性股骨头坏死大鼠骨组织及PI3K/Akt信号转导通路的影响[J]. 蚌埠医学院学报, 2019, 44(11):1441-1444. DOI: 10.13898/j.cnki.issn.1000-2200.2019.11.002 .
	ZENG S L, SHI N B, LIU Y. Effect of puerarin on the bone tissue and PI3K/Akt signal transduction pathway in rats with femoral head osteonecrosis induced by hormone[J]. J Bengbu Med Coll, 2019, 44(11):1441-1444. DOI: 10.13898/j.cnki.issn.1000-2200.2019.11.002 .
38	YUAN S Y, SHENG T, LIU L Q, et al. Puerarin prevents bone loss in ovariectomized mice and inhibits osteoclast formation in vitro [J]. Chin J Nat Med, 2016, 14(4):265-269. DOI: 10.1016/S1875-5364(16)30026-7 .
39	牛士贞, 牛通, 倪勇, 等. 葛根素注射液联合雌二醇注射液对大鼠骨质疏松性骨折愈合的影响[J]. 中国临床药理学杂志, 2019, 35(23):3077-3080. DOI: 10.13699/j.cnki.1001-6821.2019.23.034 .
	NIU S Z, NIU T, NI Y, et al. Effect of puerarin injection combined with estradiol injection on healing of osteoporotic fracture in rats[J]. Chin J Clin Pharmacol, 2019, 35(23):3077-3080. DOI: 10.13699/j.cnki.1001-6821.2019.23.034 .
40	黄彤, 金邦荃, 孙桂菊, 等. 葛根素对去卵巢大鼠骨密度和骨强度的改善[J]. 现代预防医学, 2010, 37(20):3894-3896.
	HUANG T, JIN B Q, SUN G J, et al. Effects of puerarin on osteoporosis of ovariectomized rats[J]. Mod Prev Med, 2010, 37(20):3894-3896.
41	TANG W K, XIAO L, GE G R, et al. Puerarin inhibits titanium particle-induced osteolysis and RANKL-induced osteoclastogenesis via suppression of the NF-κB signaling pathway[J]. J Cell Mol Med, 2020, 24(20):11972-11983. DOI: 10.1111/jcmm.15821 .
42	陈文明, 胡芯源. 葛根素联合阿仑膦酸钠对绝经后骨质疏松大鼠氧化应激、炎症反应及骨代谢的影响[J]. 中国骨质疏松杂志, 2021, 27(1):73-76, 100. DOI: 10.3969/j.issn.1006-7108.2021.01.016 .
	CHEN W M, HU X Y. Effect of puerarin combined with alendronate on oxidative stress, inflammation reaction, and bone metabolism in postmenopausal osteoporotic rats[J]. Chin J Osteoporos, 2021, 27(1):73-76, 100. DOI: 10.3969/j.issn.1006-7108.2021.01.016 .
43	YANG X, YANG Y, ZHOU S, et al. Puerarin stimulates osteogenic differentiation and bone formation through the ERK1/2 and p38-MAPK signaling pathways[J]. Curr Mol Med, 2018, 17(7):488-496. DOI: 10.2174/1566524018666171219101142 .
44	李旭炯, 张翠英. 葛根素对去卵巢大鼠骨密度及血清IL-6的影响[J]. 长治医学院学报, 2009, 23(1):13-15. DOI: 10.3969/j.issn.1006-0588.2009.01.005 .
	LI X J, ZHANG C Y. Effects of puerarin on bone mineral density and IL-6 in ovariectomized rats[J]. J Changzhi Med Coll, 2009, 23(1):13-15. DOI: 10.3969/j.issn.1006-0588.2009.01.005 .
45	许晓山, 庞正宝, 杨军, 等. 葛根素治疗去卵巢小鼠骨量丢失的疗效及对RANKL/RANK/OPG信号通路的影响[J]. 浙江医学, 2021, 43(5):471-474, 481. DOI: 10.12056/j.issn.1006-2785.2021.43.5.2020-2134 .
	XU X S, PANG Z B, YANG J, et al. Effict of puerarin on bone loss in ovariectomized mice and its effect on RANKL/RANK/OPG signaling pathway[J]. Zhejiang Med J, 2021, 43(5):471-474, 481. DOI: 10.12056/j.issn.1006-2785.2021.43.5.2020-2134 .
46	方晓燕, 李海, 顾建忠, 等. 山茶籽与葛根素对去卵巢大鼠骨质疏松的防治作用比较[J]. 中国老年学杂志, 2021, 41(2):343-345. DOI: 10.3969/j.issn.1005-9202.2021.02.034 .
	FANG X Y, LI H, GU J Z, et al. Comparison of effects of camellia seed and puerarin on osteoporosis in ovariectomized rats[J]. Chin J Gerontol, 2021, 41(2):343-345. DOI: 10.3969/j.issn.1005-9202.2021.02.034 .
47	黄延玲, 石凤英. 葛根素对去卵巢大鼠骨密度和骨代谢生化指标的影响[J]. 中国临床康复, 2004, 8(12):2307-2309.
	HUANG Y L, SHI F Y. Effects of puerarin on the bone mineral density and biochemical markers of bone metabolism in ovariectomized rats[J]. Chin J Clin Rehabil, 2004, 8(12):2307-2309.
48	高玉海, 杨芳芳, 游丽娟, 等. 淫羊藿苷与葛根素的复方药对生长期大鼠峰值骨量的影响[J]. 中华内分泌代谢杂志, 2019, 35(2):148-152. DOI: 10.3760/cma.j.issn.1000-6699.2019.02.011 .
	GAO Y H, YANG F F, YOU L J, et al. Effects of compound medicine of icariin and puerarin on peak bone mass in growing rats[J]. Chin J Endocrinol Metab, 2019, 35(2):148-152. DOI: 10.3760/cma.j.issn.1000-6699.2019.02.011 .
49	QIU Z C, LI L, HUANG Y Y, et al. Puerarin specifically disrupts osteoclast activation via blocking integrin-β3 Pyk2/Src/Cbl signaling pathway[J]. J Orthop Translat, 2022, 33:55-69. DOI: 10.1016/j.jot.2022.01.003 .
50	方志辉, 张天锋. 葛根素对骨质疏松大鼠成骨细胞增殖和活性的影响及其作用机制[J]. 广西医学, 2020, 42(20):2680-2684. DOI: 10.11675/j.issn.0253-4304.2020.20.16 .
	FANG Z H, ZHANG T F. Effect of puerarin on osteoblast proliferation and activity and its action mechanism in rats with osteoporosis[J]. Guangxi Med J, 2020, 42(20):2680-2684. DOI: 10.11675/j.issn.0253-4304.2020.20.16 .
51	王振昊, 林涨源. 葛根素联合锌治疗去势大鼠骨质疏松症的实验研究[J]. 中华全科医学, 2019, 17(9):1450-1453. DOI: 10.16766/j.cnki.issn.1674-4152.000967 .
	WANG Z H, LIN Z Y. Experimental study on treatment of osteoporosis with puerarin and zinc in ovariectomized rats[J]. Chin J Gen Pract, 2019, 17(9):1450-1453. DOI: 10.16766/j.cnki.issn.1674-4152.000967 .
52	杨占华, 郝连升, 张建新. 葛根素对骨质疏松大鼠氧化应激反应、骨代谢和骨密度的影响[J]. 中国骨质疏松杂志, 2021, 27(3):413-417. DOI: 10.3969/j.issn.1006-7108.2021.03.020 .
	YANG Z H, HAO L S, ZHANG J X. Effects of puerarin on oxidative stress response, bone metabolism, and bone mineral density in osteoporotic rats[J]. Chin J Osteoporos, 2021, 27(3):413-417. DOI: 10.3969/j.issn.1006-7108.2021.03.020 .
53	YANG Y R, CHEN D Y, LI Y L, et al. Effect of Puerarin on Osteogenic Differentiation in vitro and on New Bone Formation in vivo [J]. Drug Des Devel Ther, 2022, 16:2885-2900. DOI: 10.2147/DDDT.S379794 .
54	周昊楠, 陈远明. 葛根素防治绝经后骨质疏松症的研究进展[J]. 广西医学, 2019, 41(7):878-883. DOI: 10.11675/j.issn.0253-4304.2019.07.20 .
	ZHOU H N, CHEN Y M. Research progress of puerarin in prevention and treatment of postmenopausal osteoporosis[J]. Guangxi Med J, 2019, 41(7):878-883. DOI: 10.11675/j.issn.0253-4304.2019.07.20 .
55	LV H H, CHE T J, TANG X L, et al. Puerarin enhances proliferation and osteoblastic differentiation of human bone marrow stromal cells via a nitric oxide/cyclic guanosine monophosphate signaling pathway[J]. Mol Med Rep, 2015, 12(2):2283-2290. DOI: 10.3892/mmr.2015.3647 .
56	WANG Y, WANG W L, XIE W L, et al. Puerarin stimulates proliferation and differentiation and protects against cell death in human osteoblastic MG-63 cells via ER-dependent MEK/ERK and PI3K/Akt activation[J]. Phytomedicine, 2013, 20(10):787-796. DOI: 10.1016/j.phymed.2013.03.005 .
57	ZHANG Y, YAN M, YU Q F, et al. Puerarin prevents LPS-induced osteoclast formation and bone loss via inhibition of Akt activation[J]. Biol Pharm Bull, 2016, 39(12):2028-2035. DOI: 10.1248/bpb.b16-00522 .
58	罗琳. 葛根素联合阿仑膦酸钠治疗绝经后骨质疏松症的效果观察[J]. 中国骨质疏松杂志, 2018, 24(7):930-933, 943. DOI: 10.3969/j.issn.1006-7108.2018.07.019 .
	LUO L. Observation on the effect of puerarin combined with alendronate in the treatment of postmenopausal osteoporosis[J]. Chin J Osteoporos, 2018, 24(7):930-933, 943. DOI: 10.3969/j.issn.1006-7108.2018.07.019 .
59	彭诗洁. 葛根素配合阿仑膦酸钠治疗绝经后骨质疏松症的效果观察[J]. 西南国防医药, 2019, 29(5):543-546. DOI: 10.3969/j.issn.1004-0188.2019.05.010 .
	PENG S J. Observation on the effect of Puerarin combined with alendronate sodium in the treatment of post-menopausal osteoporosis[J]. Med J Natl Defending Forces Southwest China, 2019, 29(5):543-546. DOI: 10.3969/j.issn.1004-0188.2019.05.010 .
60	申彦菊, 沈亚非. 葛根素联合阿仑膦酸钠对绝经后骨质疏松症患者骨密度的影响[J]. 北方药学, 2019, 16(7):93-94. DOI: 10.3969/j.issn.1672-8351.2019.07.065 .
	SHEN Y J, SHEN Y F. Effect of puerarin combined with alendronate on bone mineral density in postmenopausal osteoporosis patients[J]. J N Pharm, 2019, 16(7):93-94. DOI: 10.3969/j.issn.1672-8351.2019.07.065 .

纳入研究 Included studies	动物 Animal	动物数量/只 Animal quantity n	周期/周 Period/week	动物模型 Animal model	葛根素剂量/ (mg·kg^-1) Puerarin dosage	检测部位 Detection site
Li B (2020)^[12]	SD大鼠，雌	30	14	去卵巢骨质疏松模型	50～100 (ig qd)	股骨
Li B (2022)^[13]	SD大鼠，雌	20	14	去卵巢骨质疏松模型	100 (ig qd)	股骨
Li BB (2014)^[14]	SD大鼠，雌	6	12	去卵巢骨质疏松模型	50 (ip qod)	胫骨
Guo CJ (2019)^[9]	SD大鼠，雌	12	14	链脲佐菌素诱导糖尿病模型	50 (ig qd)	股骨
QIN CY (2023)^[15]	SD大鼠，雌	6	12	去卵巢骨质疏松模型	8 (ip qd)	股骨/腰椎
Yang D (2023)^[16]	SD大鼠，雌	29	6	去卵巢骨质疏松模型	15～30 (ip qd)	股骨/腰椎
Wang GB (2020)^[17]	SD大鼠，雌	40	6	去卵巢大鼠骨折模型	35 (ih qd)	股骨
Li H (2012)^[18]	SD大鼠，雌	48	4～20	去卵巢骨质疏松模型	50 (ih qd)	股骨
Liang H (2012)^[19]	SD大鼠，雌	18	12	去卵巢骨质疏松模型	20 (ig qd)	股骨/腰椎
Liu H (2012)^[20]	SD大鼠，雌	20	12	去卵巢骨质疏松模型	5 (ip qd)	股骨
Huang HL (2011)^[21]	SD大鼠，雌	20	10～20	去卵巢骨质疏松模型	50 (ih qd)	股骨
Xi HR(1) (2018)^[22]	Wistar大鼠，雌	24	8	/	15.4 (ig qd)	股骨/椎骨/全身
Xi HR(2) (2018)^[23]	Wistar大鼠，雌	20	12	/	15.4 (ig qd)	股骨/椎骨/全身
Yue HZ (2021)^[24]	SD大鼠，雌	24	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎
Li K (2019)^[25-26]	Wistar大鼠，雌	20	4	废用性骨质疏松模型	15.4 (ig qd)	胫骨/腰椎
Xiao L (2009)^[27]	大鼠，雌	24	12	去卵巢骨质疏松模型	50 (ih qd)	股骨/胫骨/腰椎
Xiao L (2020)^[28]	C57BL/6J小鼠，雌	10	6	去卵巢骨质疏松模型	100 (ip qod)	股骨
Lyu LT (2022)^[29]	KKAY45+C57BL/6J15小鼠	30	8	链脲佐菌素诱导糖尿病模型	1.3 (ig qd)	全身
Lyu LT (2023)^[30]	Wistar大鼠，雌	30	4	去卵巢骨质疏松模型	80 (ih qd)	股骨
Wang PP (2012)^[31]	SD大鼠，雌	8	12	去卵巢骨质疏松模型	20 (ig qd)	股骨
Tian Q (2006)^[32]	SD大鼠，雌	26	7	去卵巢骨质疏松模型	20～100 (ih qd)	股骨/腰椎
Zhou Q (2006)^[33]	SD大鼠，雌	40	8	去卵巢大鼠闭合性骨折模型	5～20 (ig qd)	股骨
Yu S (2019)^[34]	SD大鼠，雌	16	8～16	去卵巢骨质疏松模型	40 (ih qd)	股骨
Zhou SH (2010)^[35]	SD大鼠，雌	20	12	去卵巢骨质疏松模型	500 (ig qd)	腰椎
Zeng SL (2018)^[36]	SD大鼠，雌	30	12	去卵巢骨质疏松模型	50～100 (ig qd)	股骨
Zeng SL (2019)^[37]	SD大鼠	20	8	激素性股骨头坏死模型	200 (ip qd)	股骨
Yuan SY (2016)^[38]	昆明小鼠，雌	32	4	去卵巢骨质疏松模型	2～8 (qd)	股骨
Niu SZ (2019)^[39]	SD大鼠，雌	28	8	去卵巢骨质疏松模型	50 (ih qd)	股骨
Huang T (2010)^[40]	SD大鼠，雌	40	12	去卵巢骨质疏松模型	5～20 (ig qd)	股骨
Tang WK (2020)^[41]	SD大鼠，雄	15	4	股骨溶解模型	15.4～30. 8 (ip qd)	股骨
Chen WM (2021)^[42]	Wistar大鼠，雌	18	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎
Yang X (2017)^[43]	SD大鼠，雌	12	12	去卵巢骨质疏松模型	4 (ig qd)	股骨
Li XJ (2009)^[44]	Wistar大鼠，雌	15	12	去卵巢骨质疏松模型	20 (ig qd)	股骨
Xu XS (2021)^[45]	C57BL/6小鼠，雌	20	8	去卵巢骨质疏松模型	100 (ig qd)	股骨
Fang XY (2021)^[46]	大鼠，雌	16	4～12	去卵巢骨质疏松模型	50 (ig qd)	股骨
Huang YL (2004)^[47]	SD大鼠，雌	16	10	去卵巢骨质疏松模型	50 (ih qd)	股骨
Gao YM (2019)^[48]	SD大鼠，雌	20	8	/	30.82 (ig qd)	股骨/全身
Qiu ZC (2022)^[49]	SD大鼠，雌	45	5～12	去卵巢骨质疏松模型	50～150 (ig qd)	胫骨
Fang ZH (2020)^[50]	SD大鼠，雌	15	3	去卵巢骨质疏松模型	50～75 (ih qd)	股骨
Wang ZH (2019)^[51]	SD大鼠，雌	20	10	去卵巢骨质疏松模型	50 (ig qd)	股骨/腰椎
Yang ZH (2021)^[52]	SD大鼠，雌	22	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎

纳入研究 Included studies	动物 Animal	动物数量/只 Animal quantity n	周期/周 Period/week	动物模型 Animal model	葛根素剂量/ (mg·kg^-1) Puerarin dosage	检测部位 Detection site
Li B (2020)^[12]	SD大鼠，雌	30	14	去卵巢骨质疏松模型	50～100 (ig qd)	股骨
Li B (2022)^[13]	SD大鼠，雌	20	14	去卵巢骨质疏松模型	100 (ig qd)	股骨
Li BB (2014)^[14]	SD大鼠，雌	6	12	去卵巢骨质疏松模型	50 (ip qod)	胫骨
Guo CJ (2019)^[9]	SD大鼠，雌	12	14	链脲佐菌素诱导糖尿病模型	50 (ig qd)	股骨
QIN CY (2023)^[15]	SD大鼠，雌	6	12	去卵巢骨质疏松模型	8 (ip qd)	股骨/腰椎
Yang D (2023)^[16]	SD大鼠，雌	29	6	去卵巢骨质疏松模型	15～30 (ip qd)	股骨/腰椎
Wang GB (2020)^[17]	SD大鼠，雌	40	6	去卵巢大鼠骨折模型	35 (ih qd)	股骨
Li H (2012)^[18]	SD大鼠，雌	48	4～20	去卵巢骨质疏松模型	50 (ih qd)	股骨
Liang H (2012)^[19]	SD大鼠，雌	18	12	去卵巢骨质疏松模型	20 (ig qd)	股骨/腰椎
Liu H (2012)^[20]	SD大鼠，雌	20	12	去卵巢骨质疏松模型	5 (ip qd)	股骨
Huang HL (2011)^[21]	SD大鼠，雌	20	10～20	去卵巢骨质疏松模型	50 (ih qd)	股骨
Xi HR(1) (2018)^[22]	Wistar大鼠，雌	24	8	/	15.4 (ig qd)	股骨/椎骨/全身
Xi HR(2) (2018)^[23]	Wistar大鼠，雌	20	12	/	15.4 (ig qd)	股骨/椎骨/全身
Yue HZ (2021)^[24]	SD大鼠，雌	24	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎
Li K (2019)^[25-26]	Wistar大鼠，雌	20	4	废用性骨质疏松模型	15.4 (ig qd)	胫骨/腰椎
Xiao L (2009)^[27]	大鼠，雌	24	12	去卵巢骨质疏松模型	50 (ih qd)	股骨/胫骨/腰椎
Xiao L (2020)^[28]	C57BL/6J小鼠，雌	10	6	去卵巢骨质疏松模型	100 (ip qod)	股骨
Lyu LT (2022)^[29]	KKAY45+C57BL/6J15小鼠	30	8	链脲佐菌素诱导糖尿病模型	1.3 (ig qd)	全身
Lyu LT (2023)^[30]	Wistar大鼠，雌	30	4	去卵巢骨质疏松模型	80 (ih qd)	股骨
Wang PP (2012)^[31]	SD大鼠，雌	8	12	去卵巢骨质疏松模型	20 (ig qd)	股骨
Tian Q (2006)^[32]	SD大鼠，雌	26	7	去卵巢骨质疏松模型	20～100 (ih qd)	股骨/腰椎
Zhou Q (2006)^[33]	SD大鼠，雌	40	8	去卵巢大鼠闭合性骨折模型	5～20 (ig qd)	股骨
Yu S (2019)^[34]	SD大鼠，雌	16	8～16	去卵巢骨质疏松模型	40 (ih qd)	股骨
Zhou SH (2010)^[35]	SD大鼠，雌	20	12	去卵巢骨质疏松模型	500 (ig qd)	腰椎
Zeng SL (2018)^[36]	SD大鼠，雌	30	12	去卵巢骨质疏松模型	50～100 (ig qd)	股骨
Zeng SL (2019)^[37]	SD大鼠	20	8	激素性股骨头坏死模型	200 (ip qd)	股骨
Yuan SY (2016)^[38]	昆明小鼠，雌	32	4	去卵巢骨质疏松模型	2～8 (qd)	股骨
Niu SZ (2019)^[39]	SD大鼠，雌	28	8	去卵巢骨质疏松模型	50 (ih qd)	股骨
Huang T (2010)^[40]	SD大鼠，雌	40	12	去卵巢骨质疏松模型	5～20 (ig qd)	股骨
Tang WK (2020)^[41]	SD大鼠，雄	15	4	股骨溶解模型	15.4～30. 8 (ip qd)	股骨
Chen WM (2021)^[42]	Wistar大鼠，雌	18	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎
Yang X (2017)^[43]	SD大鼠，雌	12	12	去卵巢骨质疏松模型	4 (ig qd)	股骨
Li XJ (2009)^[44]	Wistar大鼠，雌	15	12	去卵巢骨质疏松模型	20 (ig qd)	股骨
Xu XS (2021)^[45]	C57BL/6小鼠，雌	20	8	去卵巢骨质疏松模型	100 (ig qd)	股骨
Fang XY (2021)^[46]	大鼠，雌	16	4～12	去卵巢骨质疏松模型	50 (ig qd)	股骨
Huang YL (2004)^[47]	SD大鼠，雌	16	10	去卵巢骨质疏松模型	50 (ih qd)	股骨
Gao YM (2019)^[48]	SD大鼠，雌	20	8	/	30.82 (ig qd)	股骨/全身
Qiu ZC (2022)^[49]	SD大鼠，雌	45	5～12	去卵巢骨质疏松模型	50～150 (ig qd)	胫骨
Fang ZH (2020)^[50]	SD大鼠，雌	15	3	去卵巢骨质疏松模型	50～75 (ih qd)	股骨
Wang ZH (2019)^[51]	SD大鼠，雌	20	10	去卵巢骨质疏松模型	50 (ig qd)	股骨/腰椎
Yang ZH (2021)^[52]	SD大鼠，雌	22	6	去卵巢骨质疏松模型	35 (ih qd)	股骨/腰椎

纳入研究 Included studies	评估内容 Evaluation contents										评分 Score
纳入研究 Included studies	1	2	3	4	5	6	7	8	9	10	评分 Score
Li B (2020)^[12]				√		√		√	√	√	5
Li B (2022)^[13]				√		√		√	√	√	5
Li BB (2014)^[14]				√		√			√	√	4
Guo CJ (2019)^[9]				√		√			√	√	4
QIN CY (2023)^[15]						√		√	√	√	4
Yang D (2023)^[16]						√		√	√	√	4
Wang GB (2020)^[17]						√		√	√	√	4
Li H (2012)^[18]				√		√		√	√	√	5
Liang H (2012)^[19]						√		√	√	√	4
Liu H (2012)^[20]						√		√	√	√	4
Huang HL (2011)^[21]				√		√		√	√	√	5
Xi HR(1) (2018)^[22]	√			√		√		√	√	√	6
Xi HR(2) (2018)^[23]	√					√		√	√	√	5
Yue HZ (2021)^[24]	√					√		√	√	√	5
Li K (2019)^[25-26]	√					√		√	√	√	5
Xiao L (2009)^[27]				√		√		√	√	√	5
Xiao L (2020)^[28]						√			√	√	3
Lyu LT (2022)^[29]				√		√		√	√	√	5
Lyu LT (2023)^[30]	√					√		√	√	√	5
Wang PP (2012)^[31]						√		√	√	√	4
Tian Q (2006)^[32]						√		√	√	√	4
Zhou Q (2006)^[33]	√					√		√	√	√	5
Yu S (2019)^[34]						√		√	√	√	4
Zhou SH (2010)^[35]						√		√	√	√	4
Zeng SL (2018)^[36]						√		√	√	√	4
Zeng SL (2019)^[37]						√		√	√	√	4
Yuan SY (2016)^[38]				√		√		√	√	√	5
Niu SZ (2019)^[39]						√		√	√	√	4
Huang T (2010)^[40]						√		√	√	√	4
Tang WK (2020)^[41]						√		√	√	√	4
Chen WM (2021)^[42]				√		√		√	√	√	5
Yang X (2017)^[43]				√		√		√	√	√	5
Li XJ (2009)^[44]						√		√	√	√	4
Xu XS (2021)^[45]	√					√		√	√	√	5
Fang XY (2021)^[46]				√		√		√	√	√	5
Huang YL (2004)^[47]						√		√	√	√	4
Gao YM (2019)^[48]						√		√	√	√	4
Qiu ZC (2022)^[49]	√			√		√		√	√	√	6
Fang ZH (2020)^[50]				√		√		√	√	√	5
Wang ZH (2019)^[51]						√		√	√	√	4
Yang ZH (2021)^[52]	√					√		√	√	√	5

纳入研究 Included studies	评估内容 Evaluation contents										评分 Score
纳入研究 Included studies	1	2	3	4	5	6	7	8	9	10	评分 Score
Li B (2020)^[12]				√		√		√	√	√	5
Li B (2022)^[13]				√		√		√	√	√	5
Li BB (2014)^[14]				√		√			√	√	4
Guo CJ (2019)^[9]				√		√			√	√	4
QIN CY (2023)^[15]						√		√	√	√	4
Yang D (2023)^[16]						√		√	√	√	4
Wang GB (2020)^[17]						√		√	√	√	4
Li H (2012)^[18]				√		√		√	√	√	5
Liang H (2012)^[19]						√		√	√	√	4
Liu H (2012)^[20]						√		√	√	√	4
Huang HL (2011)^[21]				√		√		√	√	√	5
Xi HR(1) (2018)^[22]	√			√		√		√	√	√	6
Xi HR(2) (2018)^[23]	√					√		√	√	√	5
Yue HZ (2021)^[24]	√					√		√	√	√	5
Li K (2019)^[25-26]	√					√		√	√	√	5
Xiao L (2009)^[27]				√		√		√	√	√	5
Xiao L (2020)^[28]						√			√	√	3
Lyu LT (2022)^[29]				√		√		√	√	√	5
Lyu LT (2023)^[30]	√					√		√	√	√	5
Wang PP (2012)^[31]						√		√	√	√	4
Tian Q (2006)^[32]						√		√	√	√	4
Zhou Q (2006)^[33]	√					√		√	√	√	5
Yu S (2019)^[34]						√		√	√	√	4
Zhou SH (2010)^[35]						√		√	√	√	4
Zeng SL (2018)^[36]						√		√	√	√	4
Zeng SL (2019)^[37]						√		√	√	√	4
Yuan SY (2016)^[38]				√		√		√	√	√	5
Niu SZ (2019)^[39]						√		√	√	√	4
Huang T (2010)^[40]						√		√	√	√	4
Tang WK (2020)^[41]						√		√	√	√	4
Chen WM (2021)^[42]				√		√		√	√	√	5
Yang X (2017)^[43]				√		√		√	√	√	5
Li XJ (2009)^[44]						√		√	√	√	4
Xu XS (2021)^[45]	√					√		√	√	√	5
Fang XY (2021)^[46]				√		√		√	√	√	5
Huang YL (2004)^[47]						√		√	√	√	4
Gao YM (2019)^[48]						√		√	√	√	4
Qiu ZC (2022)^[49]	√			√		√		√	√	√	6
Fang ZH (2020)^[50]				√		√		√	√	√	5
Wang ZH (2019)^[51]						√		√	√	√	4
Yang ZH (2021)^[52]	√					√		√	√	√	5

分组 Group	纳入研究/篇 Included studies/piece	动物数量/只 Animal quantity （n）	I²值 I square	效应模型 Effect model	效应量 Effect size	效应量（95%CI） Effect size (95% confidence interval)	P值 P value
给药方式Tyeps of administration
口服Oral	18	397	75	随机效应	SMD	2.30 (1.73, 2.88)	<0.001
皮下注射Hypodermic injection	13	327	86	随机效应	SMD	1.68 (0.90, 2,45)	<0.001
腹腔注射Intraperitoneal injection	6	100	71	随机效应	SMD	2.57 (1.43, 3.70)	0.004
给药剂量Dosage
≤20 mg/kg	15	296	75	随机效应	SMD	2.00 (1.35, 2.64)	<0.001
20～50 mg/kg	23	476	80	随机效应	SMD	2.23 (1.65, 2.80)	<0.001
＞50 mg/kg	6	104	89	随机效应	SMD	2.29 (0.29, 4.28)	0.020
治疗周期Therapy period
≤8 weeks	22	487	83	随机效应	SMD	2.11 (1.50, 2.72)	<0.001
＞8 weeks	18	353	70	随机效应	SMD	2.06 (1.53, 2.58)	<0.001
动物模型Animal model
未造模Blank model	3	64	88	随机效应	SMD	3.21 (0.93, 5.49)	0.006
去卵巢Ovariectomized	30	693	79	随机效应	SMD	1.90 (1.45, 2.35)	<0.001
其他模型Other models	4	67	69	随机效应	SMD	3.28 (1.79, 4.77)	<0.001
葛根素来源Source of puerarin
单体成分Monomer component	18	396	77	随机效应	SMD	2.36 (1.76, 2.96)	<0.001
药品注射剂Drug injection	15	344	85	随机效应	SMD	1.86 (1.11, 2.61)	<0.001
其他Others	4	84	64	随机效应	SMD	1.93 (0.87, 2.99)	<0.001