双膦酸盐治疗骨质疏松症与总死亡率相关性的meta分析

doi:10.3877/cma.j.issn.2096-0263.2020.05.010

目的

系统评价临床随机对照试验是否能够证明双膦酸盐类药物的应用与骨质疏松症患者的死亡率降低相关。

方法

依据Meta分析要求，对CBM、CNKI、MEDLINE、PubMed、Springer、Embase、万方、维普、Cochrane Library、中国科技论文统计与分析网、专利数据库等进行检索，严格评价纳入以双膦酸盐药物作为主要干预措施治疗骨质疏松症的临床随机对照实验研究文献，并收录有效的相关的数据资料，检索年限从建库至2020年5月。采用NOS文献质量评价标准对符合纳入排除标准的文献进行质量评价。采用RR值及其95%可信区间评估关联强度。根据是否存在异质性，采用固定效应模型合并效应量，并根据单因素敏感性分析法进行敏感性分析。

结果

最终纳入21篇文献，受试者共42 849例，双膦酸盐组患者22 605例，死亡855例，安慰剂组20 244例，死亡880例。双膦酸盐治疗骨质疏松症与总死亡率相关性的为RR=0.949（95% CI：0.866，1.040，P=0.264）。阿仑膦酸盐治疗骨质疏松症与总死亡率相关性的为RR=0.996（95% CI：0.705，1.407，P=0.982），伊班膦酸盐为RR=0.802（95% CI：0.496，1.298，P=0.369），利塞膦酸盐为RR=0.915（95% CI：0.757，1.105，P=0.354），唑来膦酸盐为RR=0.898（95% CI：0.770，1.047，P=0.168），尚未发现双磷酸盐治疗骨质疏松症与总死亡率的关联性。

结论

经meta分析发现双膦酸盐治疗骨质疏松症患者的总死亡率未见明显降低。

关键词: 骨质疏松症, 双膦酸盐, 总死亡率

Objective

To systematically evaluate whether clinical randomized controlled trials can demonstrate that bisphosphonates, especially zoledronic acid, are associated with reduced mortality in patients with osteoporosis.

Methods

According to the requirements of meta-analysis, CBM, CNKI, MEDLINE, PubMed, Springer, EMBASE, Wanfang, VIP and Cochrane were analyzed Library, China Science and Technology Papers Statistics and analysis network, patent database, etc. were searched to strictly evaluate the included clinical randomized controlled trials with bisphosphonates as the main intervention measures in the treatment of osteoporosis, and included effective related data. The retrieval period was from the establishment of the database to may 2020. The NOS standard was used to evaluate the quality of the literatures that met the inclusion and exclusion criteria. RR and its 95% confidence interval were used to evaluate the association strength. According to the existence of heterogeneity, the fixed effect model was used to merge the effect amount, and the single factor sensitivity analysis method was used to analyze the sensitivity.

Results

A total of 21 articles including 42, 849 subjects, 22, 605 patients in the bisphosphonate group, 855 patients died, 20, 244 patients in the placebo group and 880 deaths in the placebo group were analyzed. The correlation between bisphosphonate therapy and total mortality was 0.949 (95% CI: 0.866, 1.040, P=0.264). The correlation between alendronate and total mortality was 0.996 (95% CI: 0.705, 1.407, P=0.982), ibandronate was RR=0.802 (95% CI: 0.496, 1.298, P=0.369), risedronate was RR=0.915 (95% CI: 0.757, 1.105, P=0.354) and zoledronate was RR=0.898 (95% CI: 0.770, 1.047, P=0.168). There was no association between bisphosphonate therapy and total mortality.

Conclusion

The meta-analysis showed that bisphosphonates did not reduce the overall mortality of patients with osteoporosis.

Key words: Osteoporosis, Bisphosphonates, Total mortality

图1 纳入文献流程图

表1 纳入文献特征表

编号	第一作者	发表年份	药物	用药时间，年	治疗组		安慰剂组		年龄	评分
编号	第一作者	发表年份	药物	用药时间，年	死亡	全部	死亡	全部	年龄	评分
1	Liberman^[14]	1995	阿仑膦酸盐	3	3	579	2	397	64（45～80）	7
2	Black^[15]	1996	阿仑膦酸盐	3	24	1 022	21	1 005	71（55～81）	8
3	Ravn^[16]	1996	伊班膦酸盐	1	1	150	40	2 218	68（54～81）	9
4	Cummings^[17]	1998	阿仑膦酸盐	4.5	37	2 214	0	280	65（≤85）	7
5	Harris^[18]	1999	利塞膦酸盐	3	15	813	249	2 796	80（≥75）	9
6	Reginster^[19]	2000	利塞膦酸盐	3	11	407	1	30	65（<75）	6
7	McClung^[20]	2001	利塞膦酸盐	3	167	3 104	10	975	69（55～80）	8
8	Chesnut^[21]	2004	伊班膦酸盐	3	19	1 954	13	949	67（55～76）	8
9	Recker^[22]	2004	伊班膦酸盐	3	23	1 911	0	83	54（45～60）	6
10	McCloskey^[23]	2007	氯膦酸盐	3	264	2 796	3	63	51（NA）	6
11	V?lim?ki^[24]	2007	利塞膦酸盐	2	0	115	16	815	69（≤85）	7
12	Black^[25]	2007	唑来膦酸盐	3	130	3 862	17	407	71（≤85）	7
13	Lyles^[26]	2007	唑来膦酸盐	1.9	101	1 054	178	3 134	78（70～100）	9
14	Yan^[27]	2009	阿仑膦酸盐	1	0	280	0	55	66（NA）	6
15	McClung^[28]	2009	伊班膦酸盐	1	0	77	3	93	61（36～84）	6
16	Boonen^[29]	2009	利塞膦酸盐	2	2	191	112	3 852	73（65～89）	9
17	Smerud^[30]	2012	伊班膦酸盐	1	0	66	141	1 057	75（≥50）	7
18	Boonen^[31]	2012	唑来膦酸盐	2	15	588	18	611	NA（50～85）	7
19	Greenspan^[32]	2015	唑来膦酸盐	2	14	89	12	92	85（≥65）	6
20	Nakamura^[33]	2017	唑来膦酸盐	2	2	333	3	332	74（65～89）	7
21	Reid^[34]	2018	唑来膦酸盐	6	27	1 000	41	1 000	71（>65）	8

表1 纳入文献特征表

编号	第一作者	发表年份	药物	用药时间，年	治疗组		安慰剂组		年龄	评分
编号	第一作者	发表年份	药物	用药时间，年	死亡	全部	死亡	全部	年龄	评分
1	Liberman^[14]	1995	阿仑膦酸盐	3	3	579	2	397	64（45～80）	7
2	Black^[15]	1996	阿仑膦酸盐	3	24	1 022	21	1 005	71（55～81）	8
3	Ravn^[16]	1996	伊班膦酸盐	1	1	150	40	2 218	68（54～81）	9
4	Cummings^[17]	1998	阿仑膦酸盐	4.5	37	2 214	0	280	65（≤85）	7
5	Harris^[18]	1999	利塞膦酸盐	3	15	813	249	2 796	80（≥75）	9
6	Reginster^[19]	2000	利塞膦酸盐	3	11	407	1	30	65（<75）	6
7	McClung^[20]	2001	利塞膦酸盐	3	167	3 104	10	975	69（55～80）	8
8	Chesnut^[21]	2004	伊班膦酸盐	3	19	1 954	13	949	67（55～76）	8
9	Recker^[22]	2004	伊班膦酸盐	3	23	1 911	0	83	54（45～60）	6
10	McCloskey^[23]	2007	氯膦酸盐	3	264	2 796	3	63	51（NA）	6
11	V?lim?ki^[24]	2007	利塞膦酸盐	2	0	115	16	815	69（≤85）	7
12	Black^[25]	2007	唑来膦酸盐	3	130	3 862	17	407	71（≤85）	7
13	Lyles^[26]	2007	唑来膦酸盐	1.9	101	1 054	178	3 134	78（70～100）	9
14	Yan^[27]	2009	阿仑膦酸盐	1	0	280	0	55	66（NA）	6
15	McClung^[28]	2009	伊班膦酸盐	1	0	77	3	93	61（36～84）	6
16	Boonen^[29]	2009	利塞膦酸盐	2	2	191	112	3 852	73（65～89）	9
17	Smerud^[30]	2012	伊班膦酸盐	1	0	66	141	1 057	75（≥50）	7
18	Boonen^[31]	2012	唑来膦酸盐	2	15	588	18	611	NA（50～85）	7
19	Greenspan^[32]	2015	唑来膦酸盐	2	14	89	12	92	85（≥65）	6
20	Nakamura^[33]	2017	唑来膦酸盐	2	2	333	3	332	74（65～89）	7
21	Reid^[34]	2018	唑来膦酸盐	6	27	1 000	41	1 000	71（>65）	8

图3 双磷酸盐治疗骨质疏松症与总死亡率相关性的发表偏倚漏斗图

图6 伊班膦酸盐总死亡率的森林图

图8 唑来膦酸盐治疗骨质疏松症与总死亡率相关性的森林图

1	中国健康促进基金会骨质疏松防治中国白皮书编委会骨质疏松症中国白皮书[J].中华健康管理学杂志, 3: 148-154.
2	Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis [J]. Am J Med, 1993, 94: 646-650.
3	NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, March 7-29, 2000: Highlights of the Conference [J]. South Med J, 2001, 94: 569-573.
4	Russell RG, Watts NB, Ebetino FH, el al. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy [J]. OsteoporosInt, 2008, 19(6): 733-759.
5	Russell RG. Bisphosphonates: the first 40 years [J]. Bone, 2011, 49(1): 2-19.
6	Bone HG, Hosking D, Devogelaer JP, et al. Ten years' experience with alendronate for osteoporosis in postmenopausal women [J]. N Engl J Med, 2004, 350(12): 1189-1199.
7	Lyles KW, Colon-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture [J]. N Engl J Med, 2007, 357(18): 1799-1809.
8	McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group [J]. N Engl J Med, 2001, 344(5): 333-340.
9	Chesnut CH, Skag A, Christiansen C, et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis [J]. J Bone Miner Res, 2004, 19 (8): 1241-1249.
10	Harris ST, Watts NB, Jackson RD, et al. Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy [J]. Am J Med, 1993, 95(6): 557-567.
11	Gu JM, Wang L, Lin H, et al. The efficacy and safety of weekly 35-mg risedronate dosing regimen for Chinese postmenopausal women with osteoporosis or osteopenia: 1-year data [J]. ActaPharmacol Sin, 2015, 36(7): 841-846.
12	Zhang ZL, Liao EY, Xia WB, et al. Alendronate sodium/vitamin D3 combination tablet versus calcitriol for osteoporosis in Chinese postmenopausal women: a 6-month, randomized, open-label, active-comparator-controlled study with a 6-month extension [J]. OsteoporosInt, 2015, 26(9): 2365-2374.
13	Kranenburg G, Bartstra JW, Weijmans M, et al. Bisphosphonates for cardiovascular risk reduction: A systematic review and meta-analysis [J]. Atherosclerosis, 2016, 252: 106-115.
14	Liberman UA, Weiss SR, Broll J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group [J]. N Engl J Med, 1995, 333(22): 1437-1443.
15	Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group [J]. Lancet, 1996, 348(9041): 1535-1541.
16	Ravn P, Clemmesen B, Riis BJ, et al. The effect on bone mass and bone markers of different doses of ibandronate: a new bisphosphonate for prevention and treatment of postmenopausal osteoporosis: a 1-year, randomized, double-blind, placebo-controlled dose-finding study [J]. Bone, 1996, 19(5): 527-533.
17	Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial [J]. JAMA, 1998, 280(24): 2077-2082.
18	Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy WithRisedronate Therapy (VERT) Study Group [J]. JAMA, 1999, 282(14): 1344-1352.
19	Reginster J, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group [J]. OsteoporosInt, 2000, 11(1): 83-91.
20	McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group [J]. N Engl J Med. 2001, 344(5): 333-340.
21	Chesnut CH, Skag A, Christiansen C, et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis [J]. J Bone Miner Res, 2004, 19(8): 1241-1249.
22	Recker R, Stakkestad JA, Chesnut CH, et al.Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis [J]. Bone, 2004, 34(5): 890-899.
23	McCloskey EV, Beneton M, Charlesworth D, et al. Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study [J]. J Bone Miner Res, 2007, 22(1): 135-141.
24	Valimaki MJ, Farrerons-Minguella J, Halse J, et al. Effects of risedronate 5 mg/d on bone mineral density and bone turnover markers in late-postmenopausal women with osteopenia: a multinational, 24-month, randomized, double-blind, placebo-controlled, parallel-group, phase III trial [J]. ClinTher, 2007, 29(9): 1937-1949.
25	Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis [J]. N Engl J Med, 2007, 356(18): 1809-1822.
26	Lyles KW, Colon-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture [J]. N Engl J Med, 2007, 357(18): 1799-1809.
27	Yan Y, Wang W, Zhu H, et al. The efficacy and tolerability of once-weekly alendronate 70 mg on bone mineral density and bone turnover markers in postmenopausal Chinese women with osteoporosis [J]. J Bone Miner Metab, 2009, 27(4): 471-478.
28	McClung MR, Bolognese MA, Sedarati F, et al. Efficacy and safety of monthly oral ibandronate in the prevention of postmenopausal bone loss [J]. Bone, 2009, 44(3): 418-422.
29	Boonen S, Orwoll ES, Wenderoth D, et al. Once-weekly risedronate in men with osteoporosis: results of a 2-year, placebo-controlled, double-blind, multicenter study [J]. J Bone Miner Res, 2009, 24(4): 719-725.
30	Smerud KT, Dolgos S, Olsen IC, et al. A 1-year randomized, double-blind, placebo-controlled study of intravenous ibandronate on bone loss following renal transplantation [J]. Am J Transplant, 2012, 12(12): 3316-3325.
31	Boonen S, Reginster JY, Kaufman JM, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis [J]. N Engl J Med, 2012, 367(18): 1714-1723.
32	Greenspan SL, Perera S, Ferchak MA, et al. Efficacy and safety of single-dose zoledronic acid for osteoporosis in frail elderly women: a randomized clinical trial [J]. JAMA Intern Med, 2015, 175(6): 913-921.
33	Nakamura T, Fukunaga M, Nakano T, et al.: Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study) [J]. OsteoporosInt, 2017, 28(1): 389-398.
34	Reid IR, Horne AM, Mihov B, et al. Fracture Prevention with Zoledronate in Older Women with Osteopenia [J]. N Engl J Med, 2018, 379(25): 2407-2416.
35	Seriolo B, Paolino S, Casabella A, et al. Osteoporosis in the elderly [J]. Aging ClinExp Res, 2013, 25(Suppl 1): S27-29.
36	马晓龙,刘强,吴斗,等.骨质疏松显微骨折早期发生发展过程的实验研究[J/CD].中华老年骨科与康复电子杂志, 2016, 2(3): 129-135.
37	中华人民共和国国家统计局.中国统计年鉴[M].北京:中国统计出版社, 2015.
38	邱贵兴.老年骨质疏松性骨折的治疗策略[J].中华老年骨科与康复电子杂志, 2015, 1(1): 1-5.
39	Abrahamsen B, van Staa T, Ariely R, et al. Excess mortality following hip fracture: a systematic epidemiological review [J]. OsteoporosInt, 2009, 20(10): 1633-1650.
40	邵佳申,刘勃,李佳,等. 2010至2011年河北省老年股骨转子间骨折的流行病学特征分析[J/CD].中华老年骨科与康复电子杂志, 2018, 4(6): 352-355.
41	李佳,刘勃,刘松,等.中国中西部地区2010至2011年60岁以上股骨颈骨折流行病学对比[J/CD].中华老年骨科与康复电子杂志, 2018, 4(1): 38-42.
42	刘松,李佳,李石伦,等.中国华北和华东地区2010至2011年老年股骨转子间骨折流行病学对比分析[J/CD].中华老年骨科与康复电子杂志, 2018, 4(1): 43-47.
43	刘松,陈伟,朱燕宾,等.中国东北和西北地区2010—2011年老年髋部骨折的流行病学对比[J/CD].中华老年骨科与康复电子杂志, 2017, 3(3): 172-176.
44	Si L, Winzenberg TM, Jiang Q, et al. Projection of osteoporosis-related fractures and costs in China: 2010-2050 [J]. OsteoporosInt, 2015, 26(7): 1929-1937.
45	Davidson CW, Merrilees MJ, Wilkinson TJ, et al. Hip fracture mortality and morbidity--can we do better? [J]. N Z Med J, 2001, 114(1136): 329-332.
46	Loures MAR, Zerbini CAF, Danowski JS, et al. Guidelines of the Brazilian Society of Rheumatology for the diagnosis and treatment of osteoporosis in men [J]. Rev Bras ReumatolEngl Ed, 2017, 57 (Suppl 2): 497-514.
47	Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis - 2016 [J]. EndocrPract, 2016, 22 (Suppl 4): 1-42.
48	宋会平,张柳.阿仑膦酸钠治疗老年女性严重骨质疏松症患者的疗效分析[J/CD].中华老年骨科与康复电子杂志, 2016, 2(3): 141-145.
49	Yeap SS, Hew FL, Lee JK, et al. The Malaysian Clinical Guidance on the management of postmenopausal osteoporosis, 2012: a summary [J]. Int J Rheum Dis, 2013, 16(1): 30-40.
50	Lee S, Yin RV, Hirpara H, et al. Increased risk for atypical fractures associated with bisphosphonate use [J]. FamPract, 2015, 32(3): 276-281.
51	Cremers S, Papapoulos S. Pharmacology of bisphosphonates [J]. Bone, 2011, 49(1): 42-49.
52	Schilcher J, Koeppen V, Aspenberg P, et al. Risk of atypical femoral fracture during and after bisphosphonate use [J]. N Engl J Med, 2014, 371(10): 974-976.
53	李玉洁,朱志伟,刘忠厚. 2014年骨质疏松领域进展回顾--美国骨矿盐研究学会（ASBMR）年会精粹（2014，休斯顿）[J].中国骨质疏松杂志, 2015, 21(4): 379-394.
54	Borromeo GL, Brand C, Clement JG, et al. A large case-control study reveals a positive association between bisphosphonate use and delayed dental healing and osteonecrosis of the jaw [J]. J Bone Miner Res, 2014, 29(6): 1363-1368.
55	Lin TC, Yang CY, Kao Yang YH, et al. Incidence and risk of osteonecrosis of the jaw among the Taiwan osteoporosis population [J]. OsteoporosInt, 2014, 25(5): 1503-1511.
56	Chiu WY, Chien JY, Yang WS, et al. The risk of osteonecrosis of the Jaws in Taiwanese osteoporotic patients treated with oral alendronate or raloxifene [J]. J ClinEndocrinolMetab, 2014, 99(8): 2729-2735.

[1]	杨霁, 黄顺梅, 王安鸽, 吴月, 杨云梅. 杭州地区老年人群中肌少症患病情况及其与骨质疏松症的相关性分析[J]. 中华危重症医学杂志(电子版), 2023, 16(03): 207-210.
[2]	陆宜仙, 张震涛, 夏德萌, 王家林. 巨噬细胞极化在骨质疏松中调控作用及机制的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(06): 538-541.
[3]	陈跃圻, 罗睿, 向涵, 余泳妍, 余挺. 骨质疏松症与牙周炎的因果关系：一项两样本孟德尔随机化研究[J]. 中华口腔医学研究杂志(电子版), 2023, 17(04): 292-298.
[4]	王明, 陈萍. 地舒单抗导致颌骨骨坏死一例及文献复习[J]. 中华口腔医学研究杂志(电子版), 2022, 16(03): 180-183.
[5]	南方护骨联盟前列腺癌骨转移专家组. 前列腺癌骨转移诊疗专家共识（2023版）[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(03): 201-208.
[6]	倪鑫淼, 王磊, 王潇, 陈志远, 翁小东, 刘修恒. 前列腺癌患者骨保护现状及临床用药进展[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(02): 191-195.
[7]	张茜, 刘叶青, 康雪莹, 孙兵兵, 刘岩, 胡丽叶, 周亚茹. 血清铁蛋白与绝经后骨质疏松症的相关性分析[J]. 中华老年骨科与康复电子杂志, 2023, 09(03): 166-171.
[8]	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, 09(01): 23-27.
[9]	许航, 崔宇韬, 任广凯, 刘贺, 王雁冰, 彭传刚, 吴丹凯. 骨质疏松症关键基因的筛选及生物信息学分析[J]. 中华老年骨科与康复电子杂志, 2023, 09(01): 18-22.
[10]	雷礼辉, 李峰, 罗光平, 刘洪, 杨骐彰, 吴涛, 翁睿. 椎体CT值对原发性骨质疏松症唑来膦酸钠疗效的评价价值[J]. 中华老年骨科与康复电子杂志, 2022, 08(05): 285-289.
[11]	金万通, 薛海鹏, 周大鹏, 刘兵, 纪振钢, 马翔宇, 杨超, 张昊, 韩宁, 宗宇宁, 张咏晧, 马泽方. 3D打印结合PMMA骨水泥髓内支撑技术在老年肱骨近端骨质疏松性骨折中的应用[J]. 中华老年骨科与康复电子杂志, 2022, 08(05): 276-284.
[12]	蔡金辉, 叶浩翊, 申忱, 林良业, 刁凡登, 郭栋华, 刘志锋, 刘庆余. 椎体压缩骨折机会性筛查：常规胸部、腹部CT测量T₁₂、L₁椎体CT值的价值[J]. 中华老年骨科与康复电子杂志, 2022, 08(04): 217-223.
[13]	蔡林秀, 解强, 张曦, 高俊, 孔泳. 抗骨质疏松药物不同给药途径研究进展[J]. 中华老年骨科与康复电子杂志, 2022, 08(01): 60-64.
[14]	蔡莉萍, 燕琪慧, 郭蔚莹. TNF-α在绝经后骨质疏松症中的研究进展[J]. 中华临床医师杂志(电子版), 2022, 16(03): 274-279.
[15]	白晓辉, 张龙, 王永峰, 冯毅, 赵斌, 吕智, 徐朝健. 单侧与双侧经皮椎体成形术治疗Kummell病的疗效比较[J]. 中华老年病研究电子杂志, 2023, 10(02): 14-18.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

The relationship between bisphosphonates and total mortality in patients with osteoporosis: A Meta-Analysis

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

The relationship between bisphosphonates and total mortality in patients with osteoporosis: A Meta-Analysis