Efficacy and safety of romozumab in the treatment of osteoporosis in adults: a meta-analysis

doi:10.12307/2026.469

Abstract

Abstract: OBJECTIVE: Romosozumab is a novel biologic agent currently being used to treat osteoporosis in postmenopausal women at high risk of fracture. This meta-analysis aims to systematically evaluate the efficacy and safety of romosozumab compared with placebo, alendronate sodium, teriparatide, and denosumab in the treatment of osteoporosis in adults.
METHODS: The medical keywords “anti-sclerostin antibody,” “romosozumab,” “AMG 78500,” and “osteoporosis” were used to search PubMed, CNKI, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials comparing the safety and efficacy of romosozumab with alendronate, teriparatide, denosumab, or placebo in adult patients with osteoporosis, published from database inception until July 1, 2025. Two researchers independently screened eligible studies, assessed the risk of bias, and extracted data from each study. The quality of the included randomized controlled trials was evaluated using the Cochrane Collaboration’s Risk of Bias Tool for Randomized Controlled Trials. Meta-analysis was performed using review management software (RevMan version 5.4). The primary outcome for assessing anti-osteoporotic efficacy was the percentage change in bone mineral density from baseline at 6 and 12 months. Secondary outcomes included the incidence of adverse events and cardiovascular complications during treatment with anti-osteoporotic medications.
RESULTS: (1) A total of 10 randomized controlled trials involving 12 570 patients were included in the meta-analysis. (2) Compared with placebo, alendronate, and teriparatide, romosozumab significantly increased bone mineral density at the lumbar spine, total hip, and femoral neck at 6 and 12 months. Compared with denosumab, romosozumab significantly increased lumbar spine bone mineral density at 6 months (mean difference [MD]=3.68, 95% confidence interval [CI]: 0.34–7.01, P=0.03) and 12 months (MD=5.20, 95% CI: 3.19–7.21, P < 0.000 01), while no significant differences were observed in total hip or femoral neck bone mineral density at 6 and 12 months between the two treatments. (3) In terms of safety, compared with the alendronate subgroup, romosozumab had a lower incidence of adverse events (relative risk [RR]=0.96, 95% CI: 0.93-0.99, P=0.02); compared with the teriparatide subgroup, romosozumab had a higher incidence of adverse events (RR=1.13, 95% CI: 1.01–1.25, P=0.03). There were no statistically significant differences in the incidence of adverse events between romosozumab and placebo (RR=0.98, 95% CI: 0.96–1.00, P=0.11) or denosumab (RR=2.64, 95% CI: 0.74–9.36, P=0.13). (4) Most importantly, romosozumab did not significantly increase the risk of cardiovascular complications compared with other treatments (RR=1.25, 95% CI: 0.94-1.67, P=0.12).
CONCLUSION: Romosozumab can rapidly improve lumbar spine bone mineral density with an overall controllable safety profile, making it particularly suitable for adult osteoporosis patients at high fracture risk who require rapid bone mass improvement and have no cardiovascular contraindications. This meta-analysis is based on limited data and has certain limitations. More high-quality, longer-term follow-up studies are needed to validate these findings.

Key words: romosozumab, osteoporosis, menopause, cardiovascular complications, meta-analysis

CLC Number:

Wang Xiaochen, Guo Lin, Wang Changcheng, Xu Tan, Gu Mingxi. Efficacy and safety of romozumab in the treatment of osteoporosis in adults: a meta-analysis[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(35): 9294-9301.

Figures/Tables 8

性很高(I2=98%)。在亚组分析中，安慰剂亚组的研究存在高度异质性(I2=89%)，阿仑膦酸钠亚组存在中度异质性(I2=73%)，特立帕肽亚组和地舒单抗存在同质性(I2=0%)。采用随机效应模型合并分析数据，Meta分析结果显示罗莫佐单抗与其他治疗方法之间在12个月时腰椎骨密度存在显著性差异(MD=8.73，95%CI：6.49-10.98，P < 0.000 01)，见图4。罗莫佐单抗可显著增加腰椎在12个月时的骨矿物质密度骨密度(安慰剂MD=12.89，95%CI：11.01-14.76，P < 0.000 01；阿仑膦酸钠MD=8.11，95%CI：6.68-9.55，P < 0.000 01；特立帕肽MD=4.33，95%CI：3.49-5.16，P < 0.000 01；地舒单抗MD=5.20，95%CI：3.19-7.21，P < 0.000 01)。 2.3.3 干预6个月时全髋关节骨密度的百分比变化 9项研究报告了干预6个月时全髋关节骨密度从基线开始的百分比变化[12-17，19-21]，各研究之间的异质性很高(I2=80%)。在亚组分析中，安慰剂亚组的研究存在高度异质性(I2=88%)，特立帕肽亚组和地舒单抗亚组的研究存在中度异质性(I2=52%，63%)，阿仑膦酸钠亚组存在同质性(I2=0%)。采用随机效应模型合并分析数据，Meta分析结果显示罗莫佐单抗与其他治疗方法之间在干预6个月时全髋关节骨密度方面存在显著性差异(MD=2.52，95%CI： 1.90-3.14，P < 0.000 01)，见图5。与安慰剂、阿仑膦酸钠、特立帕肽相比，罗莫佐单抗可显著增加全髋关节在6个月时的骨密度(安慰剂MD=2.96，95%CI：1.81-4.11，P < 0.000 01；阿仑膦酸钠MD=2.00，95%CI：1.35-2.65，P < 0.000 01；特立帕肽MD=2.8，95%CI：2.12-3.48，P < 0.000 01)；而与地舒单抗相比，两者在干预6个月时的全髋关节骨密度无显著性差异(MD=1.20，95%CI：-1.48-3.89，P=0.38)。 2.3.4 干预12个月时全髋关节骨密度的百分比变化 8项研究报告了干预12个月时全髋关节骨密度从基线开始的百分比变化[13-18，20-21]，各研究之间的异质性很高(I2=75%)。在亚组分析中，安慰剂亚组、阿仑膦酸钠亚组的研究存在高度异质性(I2=80%，86%)，特立帕肽亚组的研究存在中度异质性(I2 =28%)，地舒单抗亚组存在同质性(I2 =0%)。采用随机效应模型合并分析数据，Meta分析结果显示罗莫佐单抗与其他治疗方法之间存在显著性差异(MD=3.19，95%CI：2.67-3.72，P < 0.000 01)，见图6。与安慰剂、阿仑膦酸钠和特立帕肽相比，罗莫佐单抗可显著增加全髋关节在干预12个月时的骨密度(安慰剂MD=3.94，95%CI：2.86-5.02，P < 0.000 01；阿仑膦酸钠MD=2.86，95%CI：1.69-4.03，P < 0.000 01；特立帕肽MD=3.18，95%CI：2.61-3.75，P < 0.000 01)；而与地舒单"

抗相比，两者在干预12个月时的全髋关节骨密度无显著性差异(MD=0.76，95%CI：-1.03-2.55，P=0.4)。 2.3.5 干预6个月时股骨颈骨密度的百分比变化 9项研究报告了干预6个月时股骨颈骨密度从基线开始的百分比变化[12-17，19-21]，各研究之间存在中度异质性(I2=58%)。在亚组分析中，地舒单抗亚组存在同质性(I2=0%)，安慰剂亚组、阿仑膦酸钠亚组的研究存在中度异质性(I2=26%，I2=38%)，特立帕肽亚组的研究存在高度异质性(I2=85%)。采用随机效应模型合并分析数据，Meta分析结果显示罗莫佐单抗与其他治疗方法之间存在显著性差异(MD=1.99，95%CI：1.35-2.64，P < 0.000 01)，见图7，与安慰剂、阿仑膦酸钠和特立帕肽相比，罗莫佐单抗可显著增加股骨颈在6个月时的骨密度(安慰剂MD=2.12，95%CI：1.40-2.84，P < 0.000 01；阿仑膦酸钠MD=1.92，95%CI：0.67-3.17，P=0.003；特立帕肽MD=2.35，95%CI：0.59-4.11，P=0.009)；而与地舒单抗相比，两者在干预6个月时的股骨颈骨密度无显著性差异(MD=-0.05，95%CI：-1.72-1.62，P=0.95)。 2.3.6 干预12个月时股骨颈骨密度的百分比变化 8项研究报告了干预12个月时股骨颈骨密度从基线开始的百分比变化[13-18，20-21]，各研究之间存在中度异质性(I2=71%)。在亚组分析中，安慰剂亚组和地舒单抗亚组存在中度异质性(I2=66%，I2=42%)，阿仑膦酸钠亚组和特立帕肽亚组的研究存在同质性(I2=11%，I2=9%)。采用随机效应模型合并分析数据，Meta分析结果显示罗莫佐单抗与其他治疗方法之间存在显著性差异(MD=3.46，95%CI：2.74-4.17，P < 0.000 01)，见图8。与安慰剂、阿仑膦酸钠和特立帕肽相比，罗莫佐单抗可显著增加股骨颈在干预12个月时的骨密度(安慰剂MD=4.74，95%CI：3.43-6.05，P < 0.000 01；阿仑膦酸钠MD=3.11，95%CI：2.65-3.57，P < 0.000 01；特立帕肽MD=3.13，95%CI：2.40-3.87，P < 0.000 01)；而与地舒单抗相比，两者在干预12个月时的股骨颈骨密度无显著性差异(MD=1.63，95%CI：-1.18-4.44，P=0.25)。 2.4 次要结果 2.4.1 不良事件发生率有9项纳入研究记录了“任何不良事件”这一结果[12-18，20-21]，1项研究只记录了严重不良事件[21]，亚组分析显示安慰剂、阿仑膦酸钠和特立帕肽、地舒单抗亚组研究之间异质性较低(均为I2=0%)，因此采用了固定效应模型合并数据。结果表明，罗莫佐单抗与其他药物的总体不良反应发生率无显著性差异(RR=0.98，95%CI：0.96-1，P=0.05)，见图9。然而亚组分析显示，与阿仑膦酸钠组相比，罗莫佐单抗的不良事件发生率较低(RR=0.96，95%CI：0.93-0.99，P=0.02)；与特立帕肽组相比，罗莫佐单抗的不良事件发生率较高(RR=1.13，95%CI：1.01-1.25，P=0.03)。而罗莫佐单抗与安慰剂、地诺单抗在不良事件发生率上无显著性差异(RR=0.98，95%CI：0.96-1.00，P=0.11；RR=2.64，95%CI：0.74-9.36，P=0.13)。 2.4.2 心血管事件发生率有4项纳入研究记录了“心血管事件”这一并发症发生情"

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