罗莫珠单抗治疗骨质疏松症疗效和安全性的meta分析

doi:10.3969/j.issn.1004-583X.2026.04.001

摘要/Abstract

摘要：

目的分析评估罗莫珠单抗治疗骨质疏松症患者的临床疗效及安全性。方法系统检索PubMed、Embase、Web of Science、Medline、the Cochrane Library、美国临床试验注册平台、CNKI、万方、维普、SinoMed等数据库,检索时间为建库起至2025年12月31日,收集有关罗莫珠单抗与安慰剂(或其他抗骨质疏松药物)对照治疗骨质疏松症的随机对照试验(RCT),提取文献有效数据及质量评价后,应用RevMan 5.3软件进行meta分析。结果共纳入11篇RCT,共计15 719例患者。Meta分析结果显示:在疗效方面,与安慰剂相比,罗莫珠单抗能显著提高骨质疏松症患者的腰椎骨密度[MD=11.75,95%CI(9.07,14.42),P<0.01]、全髋关节骨密度[MD=3.31,95%CI(1.19,5.42),P=0.002];降低新发椎体骨折发生率[RR=0.25,95%CI(0.16,0.40),P<0.01];但在提高股骨颈骨密度方面,组间差异无统计学意义。安全性方面,与安慰剂组相比,罗莫珠单抗组不良事件发生率显著更低[RR=0.97,95%CI(0.96,0.99),P=0.003];与特立帕肽组相比,两组不良事件发生率差异无统计学意义[RR=1.11,95%CI(1.00,1.23),P=0.05];与阿仑膦酸钠组不良事件发生率相近,差异无统计学意义[RR=1.00,95%CI(0.93,1.08),P=0.95]。罗莫珠单抗组与安慰剂、特立帕肽和阿仑膦酸钠严重不良事件发生率相近,差异无统计学意义。结论罗莫珠单抗可显著提高骨质疏松患者的腰椎骨密度和全髋关节骨密度水平,降低新发椎体骨折发生率,安全性良好,不良事件发生率未增加。

关键词: 骨质疏松, 骨密度, 罗莫珠单抗, Meta分析

Abstract:

Objective To evaluate the clinical efficacy and safety of romosozumab in patients with osteoporosis. Methods A systematic search was conducted in PubMed, Embase, Web of Science, Medline, the Cochrane Library, ClinicalTrials.gov, CNKI, Wanfang, VIP, and SinoMed for randomized controlled trials (RCTs) comparing romosozumab with placebo or other anti-osteoporotic drugs in the treatment of osteoporosis, from database inception to December 31, 2025. After data extraction and quality assessment of the eligible studies, meta-analysis was performed using RevMan 5.3. Results A total of 11 RCTs, including 15,719 patients, were included. The meta-analysis showed that, compared with placebo, romosozumab significantly increased lumbar spine bone mineral density (BMD) (MD=11.75, 95%CI[9.07, 14.42], P<0.01) and total hip bone mineral density (MD=3.31, 95%CI[1.19, 5.42], P=0.002), and reduced the incidence of new vertebral fractures (RR=0.25, 95%CI[0.16, 0.40], P<0.01). However, there was no statistically significant difference between groups in improving femoral neck bone mineral density. In terms of safety, the incidence of adverse events was significantly lower in the romosozumab group than in the placebo group (RR=0.97, 95%CI[0.96, 0.99], P=0.003). Compared with teriparatide, there was no statistically significant difference in the incidence of adverse events between the two groups (RR=1.11, 95%CI[1.00, 1.23], P=0.05). The incidence of adverse events was similar between the romosozumab and alendronate groups, with no statistically significant difference (RR=1.00, 95%CI[0.93, 1.08], P=0.95). The incidence of serious adverse events was similar between the romosozumab group and the placebo, teriparatide, and alendronate groups, with no statistically significant differences. Conclusion Romosozumab can significantly increase lumbar spine and total hip bone mineral density in patients with osteoporosis and reduce the incidence of new vertebral fractures. It has a favorable safety profile, with no increase in adverse event rates.

Key words: osteoporosis, bone mineral density, romosozumab, meta-analysis

中图分类号:

R681

朱瑞罡, 李浩强, 王友昆, 郭继东, 王强. 罗莫珠单抗治疗骨质疏松症疗效和安全性的meta分析[J]. 临床荟萃, 2026, 41(4): 293-300.

Zhu Ruigang, Li Haoqiang, Wang Youkun, Guo Jidong, Wang Qiang. A meta-analysis of the efficacy and safety of romosozumab in the treatment of osteoporosis[J]. Clinical Focus, 2026, 41(4): 293-300.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2026.04.001

https://www.lchc.cn/CN/Y2026/V41/I4/293

图/表 15

图1 文献筛选流程

Fig.1 Literature screening flowchart

表1 研究的基本特征

Tab. 1 Baseline characteristics of the included studies

第一作者及发表年限	组别	例数	年龄(岁)	干预措施	疗程	结局指标
Lau^[4] 2020	试验组对照组	146 129	75.2±7.0 74.0±6.7	罗莫珠单抗210 mg 阿仑膦酸钠	12个月	⑤⑥
Bente^[5] 2022	试验组对照组	1 494 1 519	70.4±7.1 70.4±6.9	罗莫珠单抗210 mg 安慰剂	12个月	④⑤⑥
Cosman^[6] 2016	试验组对照组	3 589 3 591	70.9±7.0 70.8±6.9	罗莫珠单抗210 mg 安慰剂	12个月	①②③④⑤⑥
Baek^[7] 2021	试验组对照组	34 33	66.7±7.6 68.4±7.2	罗莫珠单抗210 mg 安慰剂	6个月	①②③⑤
Ishibashi^[8] 2017	试验组对照组	63 63	68.3±5.9 67.8±7.2	罗莫珠单抗210 mg 安慰剂	12个月	①②③⑤⑥
Mcclung^[9] 2014	试验组	52	66.3±6.5	罗莫珠单抗210 mg
		51	67.1±5.8	阿仑膦酸钠	12个月	①②③⑤⑥
		55	66.8±5.7	特立帕肽
	对照组	52	67.0±6.5	安慰剂
Padhi^[10] 2013	试验组对照组	36 12	58.6±8.7 59.1±5.6	罗莫珠单抗安慰剂	13个月	⑤⑥
Lewiecki^[11] 2018	试验组对照组	163 82	72.4±7.4 71.5±6.9	罗莫珠单抗210 mg 安慰剂	12个月	⑤⑥
Saag^[12] 2017	试验组对照组	2 046 2 047	74.4±7.5 74.2±7.5	罗莫珠单抗210 mg 阿仑磷酸盐70 mg	12个月	①②③⑤⑥
Padhi^[13] 2010	试验组对照组	12 14	50.2±4.0 52.8±4.8	罗莫珠单抗安慰剂	3个月	⑤⑥
Langdahl^[14] 2017	试验组对照组	218 218	71.8±7.4 71.2±7.7	罗莫珠单抗210 mg 特立帕肽	12个月	⑤⑥

图2 偏倚风险条形图

Fig. 2 Risk-of-bias bar chart

图3 偏倚风险总图

Fig. 3 Risk-of-bias summary plot

图4 腰椎骨密度水平的meta分析

Fig. 4 Meta-analysis of lumbar spine bone mineral density

图5 全髋关节骨密度水平的meta分析

Fig. 5 Meta-analysis of total hip bone mineral density

图6 股骨颈骨密度水平的meta分析

Fig. 6 Meta-analysis of femoral neck bone mineral density

图7 新发椎体骨折发生率的meta分析

Fig.7 Meta-analysis of the incidence of new vertebral fractures

图8 罗莫珠单抗组和安慰剂组不良事件发生率的meta分析

Fig.8 Meta-analysis of adverse event incidence in the romosozumab and placebo groups

图9 罗莫珠单抗组和特立帕肽组不良事件发生率的meta分析

Fig. 9 Meta-analysis of adverse event incidence in the romosozumab and teriparatide groups

图10 罗莫珠单抗组和阿仑膦酸钠组不良事件发生率的meta分析

Fig.10 Meta-analysis of adverse event incidence in the romosozumab and alendronate groups

图11 罗莫珠单抗组和安慰剂组严重不良事件发生率的meta分析

Fig.11 Meta-analysis of serious adverse event incidence in the romosozumab and placebo

图12 罗莫珠单抗组和特立帕肽组严重不良事件发生率的meta分析

Fig.12 Meta-analysis of serious adverse event incidence in the romosozumab and teriparatide groups

图13 罗莫珠单抗组和阿仑膦酸钠组严重不良事件发生率的meta分析

Fig.13 Meta-analysis of serious adverse event incidence in the romosozumab and alendronate groups

表2 敏感性分析

Tab. 2 Sensitivity analysis

结局指标	随机效应模型		固定效应模型		去除权重大的研究		去除权重小的研究
结局指标	$M D$ / $R R$ (95% $C I$ )	$P$ 值	$M D$ / $R R$ (95% $C I$ )	$P$ 值	$M D$ / $R R$ (95% $C I$ )	$P$ 值	$M D$ / $R R$ (95% $C I$ )	$P$ 值
腰椎骨密度	11.75[9.07, 14.42]	<0.01	9.47[9.11, 9.83]	<0.01	12.56[10.09, 15.03]	<0.01	10.71[8.45, 12.97]	<0.01
不良事件发生率	0.98[0.96, 0.99]	0.004	0.97[0.96, 0.99]	0.003	0.97[0.94, 0.99]	0.005	0.97[0.96, 0.99]	0.003

表2 敏感性分析

Tab. 2 Sensitivity analysis

结局指标	随机效应模型		固定效应模型		去除权重大的研究		去除权重小的研究
结局指标	$M D$ / $R R$ (95% $C I$ )	$P$ 值	$M D$ / $R R$ (95% $C I$ )	$P$ 值	$M D$ / $R R$ (95% $C I$ )	$P$ 值	$M D$ / $R R$ (95% $C I$ )	$P$ 值
腰椎骨密度	11.75[9.07, 14.42]	<0.01	9.47[9.11, 9.83]	<0.01	12.56[10.09, 15.03]	<0.01	10.71[8.45, 12.97]	<0.01
不良事件发生率	0.98[0.96, 0.99]	0.004	0.97[0.96, 0.99]	0.003	0.97[0.94, 0.99]	0.005	0.97[0.96, 0.99]	0.003

参考文献 22

[1]	中华医学会物理医学与康复学分会. 骨质疏松症康复治疗指南(2024版)[J]. 中国循证医学杂志, 2024, 24: 626-636.doi:10.7507/1672-2531.202403173.
[2]	Tian L, Yu X. Fat, Sugar, and bone health: A complex relationship[J]. Nutrients, 2017, 9(5): 506.doi:10.3390/nu9050506.
[3]	黄彦钧, 黄诚, 沈砚主, 等. 罗莫佐单抗在骨质疏松症治疗中的应用[J]. 中华骨质疏松和骨矿盐疾病杂志, 2024, 17: 81-87.doi:10.3969/j.issn.1674-2591.2024.01.011.
[4]	Lau E, Dinavahi R, Woo YC, et al. Romosozumab or alendronate for fracture prevention in East Asian patients: A subanalysis of the phase III, randomized ARCH study[J]. Osteoporos Int, 2020, 31(4): 677-685.doi:10.1007/s00198-020-05324-0. pmid: 32047951
[5]	Bente L, Lorenz CH, Serge F, et al. Romosozumab efficacy and safety in European patients enrolled in the FRAME trial[J]. Osteoporos Int, 2022, 33(12): 2527-2536.doi:10.1007/s00198-022-06544-2.
[6]	Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis[J]. N Engl J Med, 2016, 375(16): 1532-1543.doi:10.1056/NEJMoa1607948.
[7]	Baek KH, Chung YS, Koh JM, et al. Romosozumab in Postmenopausal Korean Women with Osteoporosis: A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study[J]. Endocrinol Metab, 2021, 36(1): 60-69.doi:10.3803/EnM.2020.848.
[8]	Ishibashi H, Crittenden DB, Miyauchi A, et al. Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: A phase 2 study[J]. Bone, 2017, 103(63): 209-215.doi:10.1016/j.bone.2017.07.005.
[9]	Mcclung MR, Grauer A, Boonen S, et al. Romosozumab in Postmenopausal Women with Low Bone Mineral Density[J]. N Engl J Med, 2014, 370(5): 412-420.doi:10.1056/NEJMoa1305224.
[10]	Padhi D, Allison M, Kivitz A, et al. Multiple doses of sclerostin antibody romosozumab in healthy men and postmenopausal women with low bone mass: A randomized, double-blind, placebo-controlled study[J]. J Clin Pharmacol, 2013, 54(2): 168-178.doi:10.1002/jcph.239.
[11]	Lewiecki EM, Tomasz B, Stefan G, et al. A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis[J]. J Clin Endocrinol Metab, 2018, 103(9): 3183-3193.doi:10.1210/jc.2017-02163. pmid: 29931216
[12]	Saag KG, Petersen J, Brandi ML, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis[J]. N Engl J Med, 2017, 377(15): 1417-1427.doi:10.1056/NEJMoa1708322.
[13]	Padhi D, Jang G, Stouch B, et al. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody[J]. J Bone Miner Res, 2010, 26(1): 19-26.doi:10.1002/jbmr.173.
[14]	Langdahl B, Libanati C, Crittenden DB, et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: A randomised, open-label, phase 3 trial[J]. Lancet, 2017, 390(10102): 1585-1594.doi:10.1016/S0140-6736(17)31613-6. pmid: 28755782
[15]	U.S. Food and Drug Administration. (2019, April 9). FDA approves EVENITY^TM (romosozumab-aqqg) for the treatment of osteoporosis in postmenopausal women at high risk for fracture[EB/OL]. https://www.multivu.com/players/English/8490251-amgen-evenity-postmenopausal-osteoporosis/,2025-11-30.
[16]	Canalis E. Wnt signalling in osteoporosis: Mechanisms and novel therapeutic approaches[J]. Nat Rev Endocrinol, 2013, 9(10): 575-583.doi:10.1038/nrendo.2013.154. pmid: 23938284
[17]	Michael SO, Qing-Tian N, Chaoyang L, et al. Tissue-level mechanisms responsible for the increase in bone formation and bone volume by sclerostin antibody[J]. J Bone Miner Res, 2013, 29(6): 1424-1430.doi:10.1002/jbmr.2152.
[18]	Ke HZ, Richards WG, Li X, et al. Sclerostin and dickkopf-1 as therapeutic targets in bone diseases[J]. Endocr Rev, 2012, 33(5): 747-783.doi:10.1210/er.2011-1060. pmid: 22723594
[19]	Cristiano AFZ, Vera Lúcia S, Abergaria BH, et al. Incidence of hip fracture in Brazil and the development of a FRAX model[J]. Arch Osteoporos, 2015, 10(1): 11657.doi:10.1007/s11657-015-0224-5.
[20]	Cosman F, Crittenden DB, Ferrari S, et al. FRAME study: The foundation effect of building bone with 1 year of romosozumab leads to continued lower fracture risk after transition to denosumab[J]. J Bone Miner Res, 2018, 33(7): 1219-1226.doi:10.1002/jbmr.3427. pmid: 29573473
[21]	Kim DH, Rogers JR, Fulchino LA, et al. Bisphosphonates and risk of cardiovascular events: A meta-analysis[J]. PLoS One, 2015, 10(4): 1-13.doi:10.1371/journal.pone.0122646.
[22]	Miyauchi A, Dinavahi R, Crittenden DB, et al. Increased bone mineral density for 1year of romosozumab, vs placebo, followed by 2years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension[J]. Arch Osteoporos, 2019, 14(1): 1-13.doi:10.1007/s11657-019-0608-z.