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Comparative Study
. 2025 Jan;48(1):7-23.
doi: 10.1007/s40264-024-01475-9. Epub 2024 Sep 3.

Cardiovascular Safety of Romosozumab Compared to Commonly Used Anti-osteoporosis Medications in Postmenopausal Osteoporosis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials

Shih-Hao Cheng  1   2   3 , William Chu  2   4 , Wen-Hsiang Chou  2 , Woei-Chyn Chu  5 , Yi-No Kang  6   7   8   9
Affiliations
Comparative Study

Cardiovascular Safety of Romosozumab Compared to Commonly Used Anti-osteoporosis Medications in Postmenopausal Osteoporosis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials

Shih-Hao Cheng et al. Drug Saf. 2025 Jan.

Abstract

Introduction: The aim of this study was to investigate the cardiovascular safety of romosozumab in postmenopausal women with osteoporosis. Romosozumab, a monoclonal antibody targeting sclerostin, has been shown to increase bone mineral density and reduce the risk of osteoporotic fractures. However, in previous studies, romosozumab therapy was identified as a potential risk factor for cardiovascular events, particularly in patients with predisposing cardiovascular disease.

Methods: A systematic literature search was performed in the Cochrane Library, Embase, PubMed, and Web of Science databases to identify randomized controlled trials (RCTs) comparing the safety and efficacy of romosozumab versus alendronate, teriparatide, denosumab, or placebo in postmenopausal women with osteoporosis. Contrast-based network meta-analysis was performed using a random-effects model. The pooled estimates are presented as risk ratios with 95% confidence intervals.

Results: Of the 5282 articles retrieved, 25 RCTs were included in this review (n = 24,942), and 18 randomized controlled trials (n = 16,777) were included in the network meta-analysis. The results indicated no significant differences in cardiovascular mortality rate between romosozumab and placebo. Regarding the risk of major cardiovascular events, no significant differences were found in the direct evidence or the network meta-analysis with placebo as the reference.

Conclusion: Romosozumab might be a safe option for treating postmenopausal women with osteoporosis. The cardiovascular concerns associated with this treatment seem less significant than previously suggested, although additional real-world data are required to confirm this conclusion.

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Conflict of interest statement

Declarations. Funding: Open Access funding enabled and organized by National Yang Ming Chiao Tung University. Conflict of interest: Shih-Hao Cheng, William Chu, Wen-Hsiang Chou, Woei-Chyn Chu, Yi-No Kang declare that they have no conflict of interest. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and material: Data in this study are available to other researchers upon reasonable request to corresponding author Y.N.K. Code availability: Not applicable. Author contributions: Shih-Hao Cheng: conceptualization, data curation, investigation, interpretation, validation, writing—original draft. William Chu: interpretation, supervision, validation. Wen-Hsiang Chou: supervision. Woei-Chyn Chu: interpretation, supervision, validation, writing—review and editing. Yi-No Kang: formal analysis, visualization, writing—review and editing. All authors read and approved the final version.

Figures

Fig. 1
Fig. 1
Flow chart illustrating the study selection process for network meta-analysis. CDSR Cochrane Database of Systemic Reviews, k number of references, RCT randomized controlled trial
Fig. 2
Fig. 2
Network graphs for A cardiovascular death, B cardiovascular event, and C adverse event. Structure of the network evidence shows most pairwise comparisons consisting of direct evidence. The purple shade refers to a three-arm trial comparing teriparatide, raloxifene, and placebo
Fig. 3
Fig. 3
Forest plots of A cardiovascular death, B cardiovascular event, and C adverse event. The anti-osteoporosis drugs in this study did not result in significantly higher rates of cardiovascular death, cardiovascular events, or adverse events. CI confidence interval, RR risk ratio
Fig. 4
Fig. 4
Funnel plots of A cardiovascular death, B cardiovascular event, and C adverse event. NS non-significant
See this image and copyright information in PMC

References

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